Comparison of aortic and carotid baroreflex stimulus-response characteristics in humans

NASA Technical Reports Server (NTRS)

Smith, S. A.; Querry, R. G.; Fadel, P. J.; Weiss, M. W.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

2001-01-01

In order to characterize the stimulus-response relationships of the arterial, aortic, and carotid baroreflexes in mediating cardiac chronotropic function, we measured heart rate (HR) responses elicited by acute changes in mean arterial pressure (MAP) and carotid sinus pressure (CSP) in 11 healthy individuals. Arterial (aortic + carotid) baroreflex control of HR was quantified using ramped changes in MAP induced by bolus injection of phenylephrine (PE) and sodium nitroprusside (SN). To assess aortic-cardiac responses, neck pressure (NP) and suction (NS) were applied during PE and SN administration, respectively, to counter alterations in CSP thereby isolating the aortic baroreflex. Graded levels of NP and NS were delivered to the carotid sinus using a customized neck collar device to assess the carotid-cardiac baroreflex, independent of drug infusion. The operating characteristics of each reflex were determined from the logistic function of the elicited HR response to the induced change in MAP. The arterial pressures at which the threshold was located on the stimulus-response curves determined for the arterial, aortic and carotid baroreflexes were not significantly different (72+/-4, 67+/-3, and 72+/-4 mm Hg, respectively, P > 0.05). Similarly, the MAP at which the saturation of the reflex responses were elicited did not differ among the baroreflex arcs examined (98+/-3, 99+/-2, and 102+/-3 mm Hg, respectively). These data suggest that the baroreceptor populations studied operate over the same range of arterial pressures. This finding indicates each baroreflex functions as both an important anti-hypotensive and anti-hypertensive mechanism. In addition, this investigation describes a model of aortic baroreflex function in normal healthy humans, which may prove useful in identifying the origin of baroreflex dysfunction in disease- and training-induced conditions.

Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Snell, M.; Robertson, D.; Porta, A.; Harris, P.; Mosqueda-Garcia, R.

1998-01-01

BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

PubMed Central

Iliescu, Radu

2012-01-01

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307

Closed-loop spontaneous baroreflex transfer function is inappropriate for system identification of neural arc but partly accurate for peripheral arc: predictability analysis

PubMed Central

Kamiya, Atsunori; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2011-01-01

Abstract Although the dynamic characteristics of the baroreflex system have been described by baroreflex transfer functions obtained from open-loop analysis, the predictability of time-series output dynamics from input signals, which should confirm the accuracy of system identification, remains to be elucidated. Moreover, despite theoretical concerns over closed-loop system identification, the accuracy and the predictability of the closed-loop spontaneous baroreflex transfer function have not been evaluated compared with the open-loop transfer function. Using urethane and α-chloralose anaesthetized, vagotomized and aortic-denervated rabbits (n = 10), we identified open-loop baroreflex transfer functions by recording renal sympathetic nerve activity (SNA) while varying the vascularly isolated intracarotid sinus pressure (CSP) according to a binary random (white-noise) sequence (operating pressure ± 20 mmHg), and using a simplified equation to calculate closed-loop-spontaneous baroreflex transfer function while matching CSP with systemic arterial pressure (AP). Our results showed that the open-loop baroreflex transfer functions for the neural and peripheral arcs predicted the time-series SNA and AP outputs from measured CSP and SNA inputs, with r2 of 0.8 ± 0.1 and 0.8 ± 0.1, respectively. In contrast, the closed-loop-spontaneous baroreflex transfer function for the neural arc was markedly different from the open-loop transfer function (enhanced gain increase and a phase lead), and did not predict the time-series SNA dynamics (r2; 0.1 ± 0.1). However, the closed-loop-spontaneous baroreflex transfer function of the peripheral arc partially matched the open-loop transfer function in gain and phase functions, and had limited but reasonable predictability of the time-series AP dynamics (r2, 0.7 ± 0.1). A numerical simulation suggested that a noise predominantly in the neural arc under resting conditions might be a possible mechanism responsible for our findings. Furthermore, the predictabilities of the neural arc transfer functions obtained in open-loop and closed-loop conditions were validated by closed-loop pharmacological (phenylephrine and nitroprusside infusions) pressure interventions. Time-series SNA responses to drug-induced AP changes predicted by the open-loop transfer function matched closely the measured responses (r2, 0.9 ± 0.1), whereas SNA responses predicted by closed-loop-spontaneous transfer function deviated greatly and were the inverse of measured responses (r, −0.8 ± 0.2). These results indicate that although the spontaneous baroreflex transfer function obtained by closed-loop analysis has been believed to represent the neural arc function, it is inappropriate for system identification of the neural arc but is essentially appropriate for the peripheral arc under resting conditions, when compared with open-loop analysis. PMID:21486839

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation

PubMed Central

Tohyama, Takeshi; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

2018-01-01

Background Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Methods Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. Results In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. Conclusions LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation. PMID:29329321

Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

PubMed

Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

2018-01-01

Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

Baroreflex buffering in sedentary and endurance exercise-trained healthy men.

PubMed

Christou, Demetra D; Jones, Pamela Parker; Seals, Douglas R

2003-06-01

Baroreflex buffering plays an important role in arterial blood pressure control. Previous reports suggest that baroreflex sensitivity may be altered in endurance exercise-trained compared with untrained subjects. It is unknown, however, if in vivo baroreflex buffering is altered in the endurance exercise-trained state in humans. Baroreflex buffering was determined in 36 healthy normotensive men (18 endurance exercise-trained, 41+/-5 [SEM] years; 18 untrained, 41+/-4 years) by measuring the potentiation of the systolic blood pressure responses to a phenylephrine bolus and to incremental phenylephrine infusion during compared with before ganglionic blockade with trimethaphan. The exercise-trained men had a lower resting heart rate and higher maximal oxygen consumption and heart rate variability than the sedentary control subjects (all P=0.01). Mean levels and variability of blood pressure, cardiovagal baroreflex sensitivity (change in heart rate/change in systolic blood pressure), and basal muscle sympathetic nerve activity were not different in the two groups. The systolic blood pressure responses to phenylephrine were not different in the endurance-trained and untrained men before or during ganglionic blockade (P>0.6). Measures of baroreflex buffering with the use of a phenylephrine bolus (3.9+/-0.8 versus 4.0+/-0.7, trained versus untrained, P=0.85) and incremental infusion (2.8+/-0.4 versus 2.5+/-0.6, P=0.67) were similar in the two groups. Baroreflex buffering does not differ in endurance exercise-trained compared with untrained healthy men. These results support the concept that habitual vigorous endurance exercise does not modulate in vivo baroreflex buffering in healthy humans.

Autonomic modulation of arterial pressure and heart rate variability in hypertensive diabetic rats.

PubMed

Farah, Vera de Moura Azevedo; De Angelis, Kátia; Joaquim, Luis Fernando; Candido, Georgia O; Bernardes, Nathalia; Fazan, Rubens; Schaan, Beatriz D'Agord; Irigoyen, Maria-Claudia

2007-08-01

The aim of the present study was to evaluate the autonomic modulation of the cardiovascular system in streptozotocin (STZ)-induced diabetic spontaneously hypertensive rats (SHR), evaluating baroreflex sensitivity and arterial pressure and heart rate variability. Male SHR were divided in control (SHR) and diabetic (SHR+DM, 5 days after STZ) groups. Arterial pressure (AP) and baroreflex sensitivity (evaluated by tachycardic and bradycardic responses to changes in AP) were monitored. Autoregressive spectral estimation was performed for systolic AP (SAP) and pulse interval (PI) with oscillatory components quantified as low (LF:0.2-0.6Hz) and high (HF:0.6-3.0Hz) frequency ranges. Mean AP and heart rate in SHR+DM (131+/-3 mmHg and 276+/-6 bpm) were lower than in SHR (160+/-7 mmHg and 330+/-8 bpm). Baroreflex bradycardia was lower in SHR+DM as compared to SHR (0.55+/-0.1 vs. 0.97+/-0.1 bpm/mmHg). Overall SAP variability in the time domain (standard deviation of beat-by-beat time series of SAP) was lower in SHR+DM (3.1+/-0.2 mmHg) than in SHR (5.7+/-0.6 mmHg). The standard deviation of the PI was similar between groups. Diabetes reduced the LF of SAP (3.3+/-0.8 vs. 28.7+/-7.6 mmHg2 in SHR), while HF of SAP were unchanged. The power of oscillatory components of PI did not differ between groups. These results show that the association of hypertension and diabetes causes an impairment of the peripheral cardiovascular sympathetic modulation that could be, at least in part, responsible for the reduction in AP levels. Moreover, this study demonstrates that diabetes might actually impair the reduced buffer function of the baroreceptors while reducing blood pressure.

A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Doerr, D. F.; Convertino, V. A.

1995-01-01

We tested the hypothesis that one bout of maximal exercise performed 24 h before reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated baroreflex function was assessed in seven subjects before and after two periods of HDT separated by 11 mo. On the last day of one HDT period, subjects performed a single bout of maximal cycle ergometry (exercise). Subjects did not exercise after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was evaluated using a neck collar device. Integrated baroreflex function was assessed by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated vasoconstriction was assessed by measuring the late phase II rise in MAP. Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0 ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8 beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or exercise. The late phase II increase of MAP was 71% greater after exercise compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS).

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity.

PubMed

Kopp, Ulla C; Jones, Susan Y; DiBona, Gerald F

2008-12-01

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet.

Development of the Aortic Baroreflex in Microgravity

NASA Technical Reports Server (NTRS)

Shimizu, Tsuyoshi; Yamasaki, Masao; Waki, Hidefumi; Katsuda, Shin-ichiro; Oishi, Hirotaka; Katahira, Kiyoaki; Nagayama, Tadanori; Miyake, Masao; Miyamoto, Yukako

2003-01-01

Baroreceptors sense pressure in blood vessels and send this information to the brain. The primary baroreceptors are located in the main blood vessel leaving the heart (the aorta) and in the arteries in the neck (the carotid arteries). The brain uses information from the baroreceptors to determine whether blood pressure should be raised or lowered. These reflex responses are called baroreflexes. Changing position within a gravity field (i.e., moving from lying to sitting or standing) powerfully stimulates the baroreflexes. In weightlessness, the amount of stimuli that the baroreflexes receive is dramatically reduced. If this reduction occurs when the pathways that control the baroreflexes are being formed, it is possible that either the structure or function of the baroreceptors may be permanently changed. To study the effect of microgravity on structural and functional development of the aortic baroreflex system, we studied young rats (eight days old at launch) that flew on the Space Shuttle Columbia for 16 days. Six rats were studied on landing day; another six were studied after re-adapting to Earth's gravity for 30 days. On both landing day and 30 days after landing, we tested the sensitivity of the rats' baroreflex response. While the rats were anaesthetized, we recorded their arterial pressure, heart rate, and aortic nerve activity. After the tissues were preserved with perfusion fixation, we also examined the baroreflex structures. On landing day, we found that, compared to the controls, the flight rats had: fewer unmyelinated nerve fibers in their aortic nerves lower baroreflex sensitivity significantly lower contraction ability and wall tension of the aorta a reduced number of smooth muscle cells in the aorta. In the 30-day recovery group, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. The results show that spaceflight does affect the development of the aortic baroreflex. The sensitivity of the reflex may be suppressed; however, the function of the blood pressure control system can re-adapt to Earth's gravity if the rats return before maturation. The structural differences in the input pathway of the reflex (Le., the reduction in nerve fibers) may remain permanently.

The influence of central command on baroreflex resetting during exercise

NASA Technical Reports Server (NTRS)

Raven, Peter B.; Fadel, Paul J.; Smith, Scott A.

2002-01-01

The arterial baroreflex functions as a negative feedback system regulating blood pressure around an established operating point. Paradoxically, a parallel increase in heart rate and blood pressure manifests during exercise. Experimental evidence suggests these events are caused, in part, by a rapid resetting of the baroreflex by central command.

Does the Menstrual Cycle Influence the Sensitivity of Vagally Mediated Baroreflexes?

DTIC Science & Technology

2002-06-01

the study. Baroreflex measurements We applied sequential neck pressure and suction to modulate carotid baroreceptors , and recorded the re- sulting...the day menses began was designated day 0). At the beginning of each data collection period, sphygmomanometric blood pressures were re- corded with...between arterial pressure and R-R interval, suggesting that high levels of sympathetic nervous activity or of plasma noradrenaline may override or inhibit

Baroreflex modulation of sympathetic nerve activity to muscle in heat-stressed humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

To identify whether whole body heating alters arterial baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA and beat-by-beat arterial blood pressure were recorded in seven healthy subjects during acute hypotensive and hypertensive stimuli in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature (P < 0.01), MSNA (P < 0.01), heart rate (P < 0.01), and skin blood flow (P < 0.001), whereas mean arterial blood pressure did not change significantly (P > 0.05). During both normothermic and heat stress conditions, MSNA increased and then decreased significantly when blood pressure was lowered and then raised via intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure during heat stress (-128.3 +/- 13.9 U x beats(-1) x mmHg(-1)) was similar (P = 0.31) with normothermia (-140.6 +/- 21.1 U x beats(-1) x mmHg(-1)). Moreover, no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that arterial baroreflex modulation of MSNA and heart rate are not altered by whole body heating, with the exception of an upward shift of these baroreflex curves to accommodate changes in these variables that occur with whole body heating.

Inhibition of KATP channel activity augments baroreflex-mediated vasoconstriction in exercising human skeletal muscle

PubMed Central

Keller, David Melvin; Ogoh, Shigehiko; Greene, Shane; Olivencia-Yurvati, A; Raven, Peter B

2004-01-01

In the present investigation we examined the role of ATP-sensitive potassium (KATP) channel activity in modulating carotid baroreflex (CBR)-induced vasoconstriction in the vasculature of the leg. The CBR control of mean arterial pressure (MAP) and leg vascular conductance (LVC) was determined in seven subjects (25 ± 1 years, mean ± s.e.m.) using the variable-pressure neck collar technique at rest and during one-legged knee extension exercise. The oral ingestion of glyburide (5 mg) did not change mean arterial pressure (MAP) at rest (86 versus 89 mmHg, P > 0.05), but did appear to increase MAP during exercise (87 versus 92 mmHg, P = 0.053). However, the CBR–MAP function curves were similar at rest before and after glyburide ingestion. The CBR-mediated decrease in LVC observed at rest (∼39%) was attenuated during exercise in the exercising leg (∼15%, P < 0.05). Oral glyburide ingestion partially restored CBR-mediated vasoconstriction in the exercising leg (∼40% restoration, P < 0.05) compared to control exercise. These findings indicate that KATP channel activity modulates sympathetic vasoconstriction in humans and may prove to be an important mechanism by which functional sympatholysis operates in humans during exercise. PMID:15345750

Effect of 30-min +3 Gz centrifugation on vestibular and autonomic cardiovascular function

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Harm, Deborah L.; Rupert, A. H.

2003-01-01

INTRODUCTION: Repeated exposure to increased +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, it is not known whether such enhancements might also result from a single, more prolonged exposure to increased +Gz. Our study was designed to investigate whether baroreflex function and orthostatic tolerance are acutely improved by a single prolonged exposure to +3 Gz, and moreover, whether changes in autonomic cardiovascular function resulting from exposure to increased +Gz are correlated with changes in otolith function. METHODS: We exposed 15 healthy human subjects to +3 Gz centrifugation for up to 30 min or until symptoms of incipient G-induced loss of consciousness (G-LOC) ensued. Tests of autonomic cardiovascular function both before and after centrifugation included: 1) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; 2) carotid-cardiac baroreflex tests; 3) Valsalva tests; and 4) 30-min head-up tilt tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: Of the 15 subjects who underwent prolonged +3 Gz, 4 were intolerant to 30 min of head-up tilt before centrifugation but became tolerant to such tilt after centrifugation. The Valsalva-related baroreflex as well as a measure of the carotid-cardiac baroreflex were also enhanced after centrifugation. No significant vestibular-autonomic relationships were detected beyond a vestibular-cerebrovascular interaction reported earlier in a subset of seven participants. CONCLUSIONS: A single prolonged exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance.

Carotid baroreflex responsiveness in heat-stressed humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.

2000-01-01

The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.

Effect of Sustained Human Centrifugation on Autonomic Cardiovascular and Vestibular Function

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Benavides, Edgar W.; Harm, Deborah L.; Rupert, A. H.

2002-01-01

Repeated exposure to +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, both sustained exposure to +Gx and changes in otolith function resulting from the gravitational changes of space flight and parabolic flight may adversely affect autonomic cardiovascular function and orthostatic tolerance. HYPOTHESES: Baroreflex function and orthostatic tolerance are acutely improved by a single sustained (30 min) exposure to +3Gz but not +3Gx. Moreover, after 30 min of +3Gx, any changes that occur in autonomic cardiovascular function will relate commensurately to changes in otolith function. METHODS: Twenty-two healthy human subjects were first exposed to 5 min of +3 Gz centrifugation and then subsequently up to a total of30 min of either +3Gz (n = 15) or +3Gx (n = 7) centrifugation. Tests of autonomic cardiovascular function both before and after both types of centrifugation included: (a) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; (b) carotid-cardiac baroreflex tests; ( c) Valsalva tests; and (d) 30-min head-up tilt (HUT) tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: All four +3Gz subjects who were intolerant to HUT before centrifugation became tolerant to HUT after centrifugation. The operational point of the carotid-cardiac baroreflex and the Valsalva-related baroreflex were also enhanced in the +3Gz group but not in the +3Gx group. No significant vestibular-autonomic relationships were detected, other than a significant vestibular-cerebrovascular interaction reported previously. CONCLUSIONS: A single, sustained exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance whereas a similar exposure to +3 Gx centrifugation appears to have less effect.

Effects of heat stress on baroreflex function in humans

NASA Technical Reports Server (NTRS)

Crandall, Craig G.; Cui, Jian; Wilson, Thad E.

2003-01-01

INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

PubMed Central

Kopp, Ulla C.; Jones, Susan Y.; DiBona, Gerald F.

2008-01-01

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, −60 ± 4 vs. −77 ± 6%. Maximum gain, −4.22 ± 0.45 vs. −6.04 ± 0.90% ΔERSNA/mmHg, and the maximum value of instantaneous gain, −4.19 ± 0.45 vs. −6.04 ± 0.81% ΔERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 ± 0.2 vs. 6.1 ± 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 ± 4,900 vs. 20,900 ± 3,410%·s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet. PMID:18945951

Effects of acute exercise on attenuated vagal baroreflex function during bed rest

NASA Technical Reports Server (NTRS)

Convertino, Victor A.; Doerr, Donald F.; Guell, Antonio; Marini, J.-F.

1992-01-01

We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 deg head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally-mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4 percent (p less than 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p less than 0.05) by 10.7 +/- 3.7 percent above pre-bed rest levels and 34.3 +/- 7.9 percent above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise.

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

PubMed

Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Liang, Nan; Ishida, Tomoko

2012-08-15

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

The low frequency power of heart rate variability is neither a measure of cardiac sympathetic tone nor of baroreflex sensitivity.

PubMed

Martelli, Davide; Silvani, Alessandro; McAllen, Robin M; May, Clive N; Ramchandra, Rohit

2014-10-01

The lack of noninvasive approaches to measure cardiac sympathetic nerve activity (CSNA) has driven the development of indirect estimates such as the low-frequency (LF) power of heart rate variability (HRV). Recently, it has been suggested that LF HRV can be used to estimate the baroreflex modulation of heart period (HP) rather than cardiac sympathetic tone. To test this hypothesis, we measured CSNA, HP, blood pressure (BP), and baroreflex sensitivity (BRS) of HP, estimated with the modified Oxford technique, in conscious sheep with pacing-induced heart failure and in healthy control sheep. We found that CSNA was higher and systolic BP and HP were lower in sheep with heart failure than in control sheep. Cross-correlation analysis showed that in each group, the beat-to-beat changes in HP correlated with those in CSNA and in BP, but LF HRV did not correlate significantly with either CSNA or BRS. However, when control sheep and sheep with heart failure were considered together, CSNA correlated negatively with HP and BRS. There was also a negative correlation between CSNA and BRS in control sheep when considered alone. In conclusion, we demonstrate that in conscious sheep, LF HRV is neither a robust index of CSNA nor of BRS and is outperformed by HP and BRS in tracking CSNA. These results do not support the use of LF HRV as a noninvasive estimate of either CSNA or baroreflex function, but they highlight a link between CSNA and BRS. Copyright © 2014 the American Physiological Society.

Clinical models of cardiovascular regulation after weightlessness

NASA Technical Reports Server (NTRS)

Robertson, D.; Jacob, G.; Ertl, A.; Shannon, J.; Mosqueda-Garcia, R.; Robertson, R. M.; Biaggioni, I.

1996-01-01

After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice

PubMed Central

Becari, Christiane; Durand, Marina T.; Guimaraes, Alessander O.; Lataro, Renata M.; Prado, Cibele M.; de Oliveira, Mauro; Candido, Sarai C. O.; Pais, Paloma; Ribeiro, Mauricio S.; Bader, Michael; Pesquero, Joao B.; Salgado, Maria C. O.; Salgado, Helio C.

2017-01-01

In vitro and ex vivo experiments indicate that elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, is an alternative pathway for angiotensin II (Ang II) generation. However, the role played by ELA-2 in vivo is unclear. We examined ELA-2 knockout (ELA-2KO) mice compared to wild-type (WT) mice and determined whether ELA-2 played a role in hemodynamics [arterial pressure (AP) and heart rate (HR)], cardiocirculatory sympathovagal balance and baroreflex sensitivity. The variability of systolic arterial pressure (SAP) and pulse interval (PI) for evaluating autonomic modulation was examined for time and frequency domains (spectral analysis), whereas a symbolic analysis was also used to evaluate PI variability. In addition, baroreflex sensitivity was examined using the sequence method. Cardiac function was evaluated echocardiographically under anesthesia. The AP was normal whereas the HR was reduced in ELA-2KO mice (425 ± 17 vs. 512 ± 13 bpm from WT). SAP variability and baroreflex sensitivity were similar in both strains. The LF power from the PI spectrum (33.6 ± 5 vs. 51.8 ± 4.8 nu from WT) and the LF/HF ratio (0.60 ± 0.1 vs. 1.45 ± 0.3 from WT) were reduced, whereas the HF power was increased (66.4 ± 5 vs. 48.2 ± 4.8 nu from WT) in ELA-2KO mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2KO mice; however, the cardiac output, stroke volume, and ventricular size were reduced. These findings provide the first evidence that ELA-2 acts on the sympathovagal balance of the heart, as expressed by the reduced sympathetic modulation of HR in ELA-2KO mice. PMID:28386233

Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice.

PubMed

Becari, Christiane; Durand, Marina T; Guimaraes, Alessander O; Lataro, Renata M; Prado, Cibele M; de Oliveira, Mauro; Candido, Sarai C O; Pais, Paloma; Ribeiro, Mauricio S; Bader, Michael; Pesquero, Joao B; Salgado, Maria C O; Salgado, Helio C

2017-01-01

In vitro and ex vivo experiments indicate that elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, is an alternative pathway for angiotensin II (Ang II) generation. However, the role played by ELA-2 in vivo is unclear. We examined ELA-2 knockout (ELA-2KO) mice compared to wild-type (WT) mice and determined whether ELA-2 played a role in hemodynamics [arterial pressure (AP) and heart rate (HR)], cardiocirculatory sympathovagal balance and baroreflex sensitivity. The variability of systolic arterial pressure (SAP) and pulse interval (PI) for evaluating autonomic modulation was examined for time and frequency domains (spectral analysis), whereas a symbolic analysis was also used to evaluate PI variability. In addition, baroreflex sensitivity was examined using the sequence method. Cardiac function was evaluated echocardiographically under anesthesia. The AP was normal whereas the HR was reduced in ELA-2KO mice (425 ± 17 vs. 512 ± 13 bpm from WT). SAP variability and baroreflex sensitivity were similar in both strains. The LF power from the PI spectrum (33.6 ± 5 vs. 51.8 ± 4.8 nu from WT) and the LF/HF ratio (0.60 ± 0.1 vs. 1.45 ± 0.3 from WT) were reduced, whereas the HF power was increased (66.4 ± 5 vs. 48.2 ± 4.8 nu from WT) in ELA-2KO mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2KO mice; however, the cardiac output, stroke volume, and ventricular size were reduced. These findings provide the first evidence that ELA-2 acts on the sympathovagal balance of the heart, as expressed by the reduced sympathetic modulation of HR in ELA-2KO mice.

Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension?

PubMed Central

Bernardi, L; Passino, C; Porta, C; Anesi, E; Palladini, G; Merlini, G

2002-01-01

Objective: To investigate the possible causes of abnormal blood pressure control in light chain related (primary, AL) amyloidosis. Design: Cardiovascular, autonomic, and respiratory response to passive tilting were investigated in 51 patients with primary amyloidosis (mean (SEM) age 56 (2) years) and in 20 age matched controls. Spontaneous fluctuations in RR interval, respiration, end tidal carbon dioxide, blood pressure, and skin microcirculation were recorded during supine rest and with tilting. The values were subjected to spectral analysis to assess baroreflex sensitivity and the autonomic modulation of cardiac and vascular responses. Setting: Tertiary referral centre. Results: Autonomic modulation of the heart and blood pressure was nearly absent in the patients with amyloidosis: thus baroreflex sensitivity and the low frequency (0.1 Hz) fluctuations in all cardiovascular signals were severely reduced (p < 0.01 or more), as were respiratory fluctuations in the RR interval, and no change was observed upon tilting. Despite reduced autonomic modulation, blood pressure remained relatively stable in the amyloid group from supine to tilting. End tidal carbon dioxide was reduced in the amyloid patients (p < 0.001) indicating persistent hyperventilation; the breathing rate correlated inversely with the fall in blood pressure on tilting (p < 0.05). Conclusions: In primary amyloidosis, pronounced abnormalities in arterial baroreflexes and cardiovascular autonomic modulation to the heart and the vessels may be partly compensated for by hyperventilation at a slow breathing rate. PMID:12433892

Interaction between graviception and carotid baroreflex function in humans during parabolic flight-induced microgravity.

PubMed

Ogoh, Shigehiko; Marais, Michaël; Lericollais, Romain; Denise, Pierre; Raven, Peter B; Normand, Hervé

2018-05-10

The aim of the present study was to assess carotid baroreflex (CBR) during acute changes in otolithic activity in humans. To address this question, we designed a set of experiments to identify the modulatory effects of microgravity on CBR function at a tilt angle of -2{degree sign}, which was identified to minimize changes in central blood volume during parabolic flight. During parabolic flight at 0g and 1g, CBR function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid pulse trains of neck pressure (NP) and neck suction (NS) ranging from +40 to -80 Torr; CBR control of HR (carotid-HR) and MAP (carotid-MAP) baroreflex function curves, respectively. The maximal gain (G max ) of both carotid-HR and carotid-MAP baroreflex function curves were augmented during microgravity compared to 1g (carotid-HR, -0.53 to -0.80 beats/min/mmHg, P<0.05; carotid-MAP, -0.24 to -0.30 mmHg/mmHg, P<0.05). These findings suggest that parabolic flight-induced acute change of otolithic activity may modify CBR function and identifies that the vestibular system contributes to blood pressure regulation under fluctuations in gravitational forces.

High-cut characteristics of the baroreflex neural arc preserve baroreflex gain against pulsatile pressure.

PubMed

Kawada, Toru; Zheng, Can; Yanagiya, Yusuke; Uemura, Kazunori; Miyamoto, Tadayoshi; Inagaki, Masashi; Shishido, Toshiaki; Sugimachi, Masaru; Sunagawa, Kenji

2002-03-01

A transfer function from baroreceptor pressure input to sympathetic nerve activity (SNA) shows derivative characteristics in the frequency range below 0.8 Hz in rabbits. These derivative characteristics contribute to a quick and stable arterial pressure (AP) regulation. However, if the derivative characteristics hold up to heart rate frequency, the pulsatile pressure input will yield a markedly augmented SNA signal. Such a signal would saturate the baroreflex signal transduction, thereby disabling the baroreflex regulation of AP. We hypothesized that the transfer gain at heart rate frequency would be much smaller than that predicted from extrapolating the derivative characteristics. In anesthetized rabbits (n = 6), we estimated the neural arc transfer function in the frequency range up to 10 Hz. The transfer gain was lost at a rate of -20 dB/decade when the input frequency exceeded 0.8 Hz. A numerical simulation indicated that the high-cut characteristics above 0.8 Hz were effective to attenuate the pulsatile signal and preserve the open-loop gain when the baroreflex dynamic range was finite.

Modulation of human sinus node function by systemic hypoxia

NASA Technical Reports Server (NTRS)

Eckberg, D. L.; Bastow, H., III; Scruby, A. E.

1982-01-01

The present study was conducted to determine whether bradycardia develops during systemic hypoxia in supine conscious human volunteers when respiratory frequency and tidal volume are maintained at constant levels. The obtained results suggest that mild hypoxia provokes cardioacceleration in humans, independent of changes of ventilation or baroreflex responsiveness. The earliest cardioacceleration is more prominent in the inspiratory than in the expiratory phase of respiration, and occurs with very small reductions of arterial oxygen saturation. Moderate systemic hypoxia dampens fluctuations of heart rate during the respiratory cycle.

Respiratory modulation of human autonomic function on Earth.

PubMed

Eckberg, Dwain L; Cooke, William H; Diedrich, André; Biaggioni, Italo; Buckey, Jay C; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Kuusela, Tom A; Tahvanainen, Kari U O; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J; Levine, Benjamin D; Adams-Huet, Beverley; Robertson, David; Blomqvist, C Gunnar

2016-10-01

We studied healthy supine astronauts on Earth with electrocardiogram, non-invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R-R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects' responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled-frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R-R interval fluctuations, which were separated by intervals that were likely to be too short and variable to be attributed to baroreflex physiology. R-R interval fluctuations at usual breathing frequencies disappear during apnoea, and thus cannot provide evidence for the existence of a central respiratory oscillation. Apnoea sets in motion a continuous and ever changing reorganization of the relations among stimulatory and inhibitory inputs and autonomic outputs, which, in our study, could not be attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor activity. We suggest that responses of healthy subjects to apnoea are driven importantly, and possibly prepotently, by changes of central respiratory motoneurone activity. The companion article extends these observations and asks the question, Might terrestrial responses to our 20 min breathing protocol find expression as long-term neuroplasticity in serial measurements made over 20 days during and following space travel? Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Respiratory modulation of human autonomic function on Earth

PubMed Central

Cooke, William H.; Diedrich, André; Biaggioni, Italo; Buckey, Jay C.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Kuusela, Tom A.; Tahvanainen, Kari U. O.; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J.; Levine, Benjamin D.; Adams‐Huet, Beverley; Robertson, David; Blomqvist, C. Gunnar

2016-01-01

Key points We studied healthy supine astronauts on Earth with electrocardiogram, non‐invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings.The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs.R‐R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea.The subjects’ responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. Abstract We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled‐frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R‐R interval fluctuations, which were separated by intervals that were likely to be too short and variable to be attributed to baroreflex physiology. R‐R interval fluctuations at usual breathing frequencies disappear during apnoea, and thus cannot provide evidence for the existence of a central respiratory oscillation. Apnoea sets in motion a continuous and ever changing reorganization of the relations among stimulatory and inhibitory inputs and autonomic outputs, which, in our study, could not be attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor activity. We suggest that responses of healthy subjects to apnoea are driven importantly, and possibly prepotently, by changes of central respiratory motoneurone activity. The companion article extends these observations and asks the question, Might terrestrial responses to our 20 min breathing protocol find expression as long‐term neuroplasticity in serial measurements made over 20 days during and following space travel? PMID:27028958

Facilitation of the arterial baroreflex by the preoptic area in anaesthetized rats.

PubMed Central

Inui, K; Nomura, J; Murase, S; Nosaka, S

1995-01-01

1. Activation of cell bodies in the ventrolateral part of the midbrain periaqueductal grey matter (PAG) facilitates the arterial baroreflex via the nucleus raphe magnus. The facilitatory effects of stimulation within the hypothalamus on the arterial baroreflex and their relation to the PAG and nucleus raphe magnus were studied in urethane- and chloralose-anaesthetized rats. 2. Systematic mapping experiments revealed that the preoptic area (POA) is the principal location in the hypothalamus of neuronal cell bodies that are responsible for the potentiation of the baroreflex. In addition to provoking hypotension and vagal bradycardia, both electrical and chemical stimulation of the POA produced facilitation of baroreflex vagal bradycardia (BVB) that was evoked by electrical stimulation of the aortic depressor nerve. Baroreflex hypotension was slightly augmented during activation of the POA in vagotomized rats. 3. Selective destruction of cell bodies either in the ventrolateral PAG or in the nucleus raphe magnus reduced facilitation of BVB by the POA. Hypotension and bradycardia due to POA stimulation were also markedly attenuated after such selective destruction. 4. In conclusion, the POA, the ventrolateral PAG and the nucleus raphe magnus constitute a functional complex that produces cardiovascular trophotropic effects including hypotension, vagal bradycardia and baroreflex facilitation. PMID:8568691

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.; Zhang, R.; Levine, B. D.

2000-01-01

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

Predominance of Intrinsic Mechanism of Resting Heart Rate Control and Preserved Baroreflex Sensitivity in Professional Cyclists after Competitive Training.

PubMed

Azevedo, Luciene Ferreira; Perlingeiro, Patricia; Hachul, Denise Tessariol; Gomes-Santos, Igor Lucas; Tsutsui, Jeane Mike; Negrao, Carlos Eduardo; De Matos, Luciana D N J

2016-01-01

Different season trainings may influence autonomic and non-autonomic cardiac control of heart rate and provokes specific adaptations on heart's structure in athletes. We investigated the influence of transition training (TT) and competitive training (CT) on resting heart rate, its mechanisms of control, spontaneous baroreflex sensitivity (BRS) and relationships between heart rate mechanisms and cardiac structure in professional cyclists (N = 10). Heart rate (ECG) and arterial blood pressure (Pulse Tonometry) were recorded continuously. Autonomic blockade was performed (atropine-0.04 mg.kg-1; esmolol-500 μg.kg-1 = 0.5 mg). Vagal effect, intrinsic heart rate, parasympathetic (n) and sympathetic (m) modulations, autonomic influence, autonomic balance and BRS were calculated. Plasma norepinephrine (high-pressure liquid chromatography) and cardiac structure (echocardiography) were evaluated. Resting heart rate was similar in TT and CT. However, vagal effect, intrinsic heart rate, autonomic influence and parasympathetic modulation (higher n value) decreased in CT (P≤0.05). Sympathetic modulation was similar in both trainings. The autonomic balance increased in CT but still showed parasympathetic predominance. Cardiac diameter, septum and posterior wall thickness and left ventricular mass also increased in CT (P<0.05) as well as diastolic function. We observed an inverse correlation between left ventricular diastolic diameter, septum and posterior wall thickness and left ventricular mass with intrinsic heart rate. Blood pressure and BRS were similar in both trainings. Intrinsic heart rate mechanism is predominant over vagal effect during CT, despite similar resting heart rate. Preserved blood pressure levels and BRS during CT are probably due to similar sympathetic modulation in both trainings.

Central angiotensin modulation of baroreflex control of renal sympathetic nerve activity in the rat: influence of dietary sodium.

PubMed

DiBona, G F

2003-03-01

Administration of angiotensin II (angII) into the cerebral ventricles or specific brain sites impairs arterial baroreflex regulation of renal sympathetic nerve activity (SNA). Further insight into this effect was derived from: (a) using specific non-peptide angII receptor antagonists to assess the role of endogenous angII acting on angII receptor subtypes, (b) microinjection of angII receptor antagonists into brain sites behind an intact blood-brain barrier to assess the role of endogenous angII of brain origin and (c) alterations in dietary sodium intake, a known physiological regulator of activity of the renin-angiotensin system (RAS), to assess the ability to physiologically regulate the activity of the brain RAS. In rats in balance on low, normal or dietary sodium intake, losartan or candesartan was injected into the lateral cerebral ventricle or the rostral ventrolateral medulla (RVLM) and the effects on basal renal SNA and the arterial baroreflex sigmoidal relationship between renal SNA and arterial pressure were determined. With both routes of administration, the effects were proportional to the activity of the RAS as indexed by plasma renin activity (PRA). The magnitude of both the decrease in basal renal SNA and the parallel resetting of arterial baroreflex regulation of renal SNA to a lower arterial pressure was greatest in low-sodium rats with highest PRA and least in high-sodium rats with lowest PRA. Disinhibition of the paraventricular nucleus (PVN) by injection of bicuculline causes pressor, tachycardic and renal sympathoexcitatory responses mediated via an angiotensinergic projection from PVN to RVLM. In comparison with responses in normal sodium rats, these responses were greatly diminished in high-sodium rats and greatly enhanced in low-sodium rats. Physiological changes in the activity of the RAS produced by alterations in dietary sodium intake regulate the contribution of endogenous angII of brain origin in the modulation of arterial baroreflex regulation of renal SNA.

The arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapy.

PubMed

Fernandes Serôdio, João; Martins Oliveira, Mário; Matoso Laranjo, Sérgio; Tavares, Cristiano; Silva Cunha, Pedro; Abreu, Ana; Branco, Luísa; Alves, Sandra; Rocha, Isabel; Cruz Ferreira, Rui

2016-06-01

Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT. The study population consisted of 25 patients with indication for CRT, aged 65±10 years, NYHA functional class ≥III in 52%, QRS width 159±15 ms, left ventricular ejection fraction (LVEF) 29±5%, left ventricular end-systolic volume (LVESV) 150±48 ml, B-type natriuretic peptide (BNP) 357±270 pg/ml, and peak oxygen consumption (peak VO2) 18.4±5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals. HF patients showed a significantly depressed BEI during tilt (31±12% vs. 49±18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB ≤25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min. Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure

PubMed Central

Jaenisch, Rodrigo B.; Hentschke, Vítor S.; Quagliotto, Edson; Cavinato, Paulo R.; Schmeing, Letiane A.; Xavier, Léder L.

2011-01-01

Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n = 8), trained sham (n = 8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P < 0.01), increased LV systolic pressure (P < 0.01), and reduced right ventricular hypertrophy (P < 0.01) and pulmonary (P < 0.001) and hepatic (P < 0.001) congestion. It also decreased resting heart rate (HR; P < 0.05), indicating a decrease in the sympathetic and an increase in the vagal modulation of HR. There was also an increase in baroreflex gain (P < 0.05). The respiratory system resistance was reduced (P < 0.001), which was associated with the reduction in tissue resistance after RMT (P < 0.01). The respiratory system and tissue elastance (Est) were also reduced by RMT (P < 0.01 and P < 0.05, respectively). Additionally, the quasistatic Est was reduced after RMT (P < 0.01). These findings show that a 6-wk RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction. PMID:21903877

Persistence of baroreceptor control of cerebral blood flow velocity at a simulated altitude of 5000 m.

PubMed

Passino, Claudio; Cencetti, Simone; Spadacini, Giammario; Quintana, Robert; Parker, Daryl; Robergs, Robert; Appenzeller, Otto; Bernardi, Luciano

2007-09-01

To assess the effects of acute exposure to simulated high altitude on baroreflex control of mean cerebral blood flow velocity (MCFV). We compared beat-to-beat changes in RR interval, arterial blood pressure, mean MCFV (by transcranial Doppler velocimetry in the middle cerebral artery), end-tidal CO2, oxygen saturation and respiration in 19 healthy subjects at baseline (Albuquerque, 1779 m), after acute exposure to simulated high altitude in a hypobaric chamber (barometric pressure as at 5000 m) and during oxygen administration (to achieve 100% oxygen saturation) at the same barometric pressure (HOX). Baroreflex control on each signal was assessed by univariate and bivariate power spectral analysis performed on time series obtained during controlled (15 breaths/min) breathing, before and during baroreflex modulation induced by 0.1-Hz sinusoidal neck suction. At baseline, neck suction was able to induce a clear increase in low-frequency power in MCFV (P<0.001) as well as in RR and blood pressure. At high altitude, MCFV, as well as RR and blood pressure, was still able to respond to neck suction (all P<0.001), compared to controlled breathing alone, despite marked decreases in end-tidal CO2 and oxygen saturation at high altitude. A similar response was obtained at HOX. Phase delay analysis excluded a passive transmission of low-frequency oscillations from arterial pressure to cerebral circulation. During acute exposure to high altitude, cerebral blood flow is still modulated by the autonomic nervous system through the baroreflex, whose sensitivity is not affected by changes in CO2 and oxygen saturation levels.

Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function.

PubMed

Funakoshi, Kouta; Hosokawa, Kazuya; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

2014-01-01

Patients with heart failure and preserved ejection fraction (HFpEF) are supersensitive to volume overload, and a striking increase in left atrial pressure (LAP) often occurs transiently and is rapidly resolved by intravascular volume reduction. The arterial baroreflex is a powerful regulator of intravascular stressed blood volume. We examined whether arterial baroreflex failure (FAIL) mimicked by constant carotid sinus pressure (CSP) causes a striking increase in LAP and systemic arterial pressure (AP) by volume loading in rats with normal left ventricular (LV) function. In anesthetized Sprague-Dawley rats, we isolated bilateral carotid sinuses and controlled CSP by a servo-controlled piston pump. We mimicked the normal arterial baroreflex by matching CSP to instantaneous AP and FAIL by maintaining CSP at a constant value regardless of AP. We infused dextran stepwise (infused volume [Vi]) until LAP reached 15 mm Hg and obtained the LAP-Vi relationship. We estimated the critical Vi as the Vi at which LAP reached 20 mm Hg. In FAIL, critical Vi decreased markedly from 19.4 ± 1.6 mL/kg to 15.6 ± 1.6 mL/kg (P < .01), whereas AP at the critical Vi increased (194 ± 6 mm Hg vs 163 ± 6 mm Hg; P < .01). We demonstrated that an artificial arterial baroreflex system we recently developed could fully restore the physiologic volume intolerance in the absence of native arterial baroreflex. Arterial baroreflex failure induces striking volume intolerance in the absence of LV dysfunction and may play an important role in the pathogenesis of acute heart failure, especially in states of HFpEF. Copyright © 2014 Elsevier Inc. All rights reserved.

The estrogen-dependent baroreflex dysfunction caused by nicotine in female rats is mediated via NOS/HO inhibition: Role of sGC/PI3K/MAPK{sub ERK}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fouda, Mohamed A.; El-Gowelli, Hanan M.; El-Gowilly, Sahar M.

We have previously reported that estrogen (E2) exacerbates the depressant effect of chronic nicotine on arterial baroreceptor activity in female rats. Here, we tested the hypothesis that this nicotine effect is modulated by nitric oxide synthase (NOS) and/or heme oxygenase (HO) and their downstream soluble guanylate cyclase (sGC)/phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinases (MAPKs) signaling. We investigated the effects of (i) inhibition or facilitation of NOS or HO on the interaction of nicotine (2 mg/kg/day i.p., 2 weeks) with reflex bradycardic responses to phenylephrine in ovariectomized (OVX) rats treated with E2 or vehicle, and (ii) central pharmacologic inhibition of sGC, PI3K,more » or MAPKs on the interaction. The data showed that the attenuation by nicotine of reflex bradycardia in OVXE2 rats was abolished after treatment with hemin (HO inducer) or L-arginine (NOS substrate). The hemin or L-arginine effect disappeared after inhibition of NOS (Nω-Nitro-L-arginine methyl ester hydrochloride, L-NAME) and HO (zinc protoporphyrin IX, ZnPP), respectively, denoting the interaction between the two enzymatic pathways. E2-receptor blockade (ICI 182,780) reduced baroreflexes in OVXE2 rats but had no effect on baroreflex improvement induced by hemin or L-arginine. Moreover, baroreflex enhancement by hemin was eliminated following intracisternal (i.c.) administration of wortmannin, ODQ, or PD98059 (inhibitors of PI3K, sGC, and extracellular signal-regulated kinases, MAPK{sub ERK}, respectively). In contrast, the hemin effect was preserved after inhibition of MAPK{sub p38} (SB203580) or MAPK{sub JNK} (SP600125). Overall, NOS/HO interruption underlies baroreflex dysfunction caused by nicotine in female rats and the facilitation of NOS/HO-coupled sGC/PI3K/MAPK{sub ERK} signaling might rectify the nicotine effect. - Highlights: • Hemin or L-arginine blunts baroreflex dysfunction caused by nicotine in OVXE2 rats. • NO/CO crosstalk mediates favorable baroreflex effect of hemin or L-arginine. • Central sGC/PI3K/MAPK{sub ERK} is required for hemin facilitation of baroreflexes. • The favorable baroreflex action of hemin is independent of estrogen receptors.« less

Effects of age on the cardiac and vascular limbs of the arterial baroreflex.

PubMed

Brown, C M; Hecht, M J; Weih, A; Neundörfer, B; Hilz, M J

2003-01-01

Healthy ageing has several effects on the autonomic control of the circulation. Several studies have shown that baroreflex-mediated vagal control of the heart deteriorates with age, but so far there is little information regarding the effect of ageing on sympathetically mediated baroreflex responses. The aim of this study was to assess the effects of ageing on baroreflex control of the heart and blood vessels. In 40 healthy volunteers, aged 20-87 years, we applied oscillatory neck suction at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was maintained at 0.25 Hz. Blood pressure, electrocardiographic RR intervals and respiration were recorded continuously. Spectral analysis was used to evaluate the magnitude of the low-frequency (0.03-0.14 Hz) and high-frequency (0.15-0.50 Hz) oscillations in the RR interval and blood pressure. Responses to neck suction were assessed as the change in power of the RR interval and blood pressure fluctuations at the stimulation frequency from baseline values. Resting low- and high-frequency powers of the RR interval decreased significantly with age (P < 0.01). However, the low-frequency power of systolic blood pressure did not correlate with age. Spontaneous baroreflex sensitivity (alpha-index) showed a significant inverse correlation with age (r = -0.46, P < 0.05). Responses of the RR interval and systolic blood pressure to 0.1 Hz neck suction stimulation were not related to age, however, the RR interval response to 0.2 Hz neck suction declined significantly with age (r = -0.61, P < 0.01). These results confirm an age-related decrease in cardiovagal baroreflex responses. However, sympathetically mediated baroreflex control of the blood vessels is preserved with age.

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Palazzolo, L.; Rimoldi, A.; Diedrich, A.; Harris, P. A.; Porta, A.; Malliani, A.; Mosqueda-Garcia, R.; Robertson, D.

2001-01-01

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

Acute baroreflex resetting and its control of blood pressure in an open loop model.

PubMed

Tan, W; Panzenbeck, M J; Zucker, I H

1989-01-01

Acute baroreflex resetting has been quantitatively studied in anesthetized dogs. Carotid sinuses were isolated bilaterally and carotid sinus conditioning pressure (CPcsp) was set at nine different levels for 20 min over a range of from 40 to 200 mm Hg. Over this range of 160 mm Hg in CPcsp, the magnitude of baroreflex resetting of set point pressure (Psp), threshold pressure (Pth) and BP50 was 32.0 +/- 5, 43.3 +/- 6 and 39.6 +/- 6 mm Hg, respectively. The extent of resetting was a non-linear function of the level of CPcsp. There is less resetting at high CPcsp. The average extent of resetting is only about 25%. In contrast to this small degree of resetting, a profound inverse relationship between the baseline pressure and the conditioning pressure was observed at the end of the conditioning period for each CPcsp. In addition, we also observed an attenuation in the buffering capacity of the baroreflex at very high or very low CPcsp. Vagotomy and aortic section did not alter baroreflex resetting. This data indicates that the baroreflex is capable of monitoring the absolute level of blood pressure during acute resetting in addition to buffering transient disturbances in arterial pressure. Based upon the results of the present experiments, the concept that acute baroreflex resetting results in an inability of the baroreflex to monitor the absolute level of arterial pressure does not appear to be valid.

Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors.

PubMed

Sun, Hao; Li, De-Pei; Chen, Shao-Rui; Hittelman, Walter N; Pan, Hui-Lin

2009-12-01

The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis.

Sensing of Blood Pressure Increase by Transient Receptor Potential Vanilloid 1 Receptors on Baroreceptors

PubMed Central

Sun, Hao; Li, De-Pei; Chen, Shao-Rui; Hittelman, Walter N.

2009-01-01

The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis. PMID:19726694

Role of aortic arch vascular mechanics in cardiovagal baroreflex sensitivity.

PubMed

Klassen, Stephen A; Chirico, Daniele; Dempster, Kylie S; Shoemaker, J Kevin; O'Leary, Deborah D

2016-07-01

Cardiovagal baroreflex sensitivity (cvBRS) measures the efficiency of the cardiovagal baroreflex to modulate heart rate in response to increases or decreases in systolic blood pressure (SBP). Given that baroreceptors are located in the walls of the carotid sinuses (CS) and aortic arch (AA), the arterial mechanics of these sites are important contributors to cvBRS. However, the relative contribution of CS and AA mechanics to cvBRS remains unclear. This study employed sex differences as a model to test the hypothesis that differences in cvBRS between groups would be explained by the vascular mechanics of the AA but not the CS. Thirty-six young, healthy, normotensive individuals (18 females; 24 ± 2 yr) were recruited. cvBRS was measured using transfer function analysis of the low-frequency region (0.04-0.15 Hz). Ultrasonography was performed at the CS and AA to obtain arterial diameters for the measurement of distensibility. Local pulse pressure (PP) was taken at the CS using a hand-held tonometer, whereas AA PP was estimated using a transfer function of brachial PP. Both cvBRS (25 ± 11 vs. 19 ± 7 ms/mmHg, P = 0.04) and AA distensibility (16.5 ± 6.0 vs. 10.5 ± 3.8 mmHg(-1) × 10(-3), P = 0.02) were greater in females than males. Sex differences in cvBRS were eliminated after controlling for AA distensibility (P = 0.19). There were no sex differences in CS distensibility (5.32 ± 2.3 vs. 4.63 ± 1.3 mmHg(-1) × 10(-3), P = 0.32). The present data demonstrate that AA mechanics are an important contributor to differences in cvBRS. Copyright © 2016 the American Physiological Society.

Involvement of arterial baroreflex in the protective effect of dietary restriction against stroke

PubMed Central

Liu, Ai-Jun; Guo, Jin-Min; Liu, Wei; Su, Feng-Yun; Zhai, Qi-Wei; Mehta, Jawahar L; Wang, Wei-Zhong; Su, Ding-Feng

2013-01-01

Dietary restriction (DR) protects against neuronal dysfunction and degeneration, and reduces the risk of ischemic stroke. This study examined the role of silent information regulator T1 (SIRT1) and arterial baroreflex in the beneficial effects of DR against stroke, using two distinct stroke models: stroke-prone spontaneously hypertensive rats (SP-SHRs) and Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Sirt1 knockout (KO) mice were used to examine the involvement of sirt1. Sinoaortic denervation was used to inactivate arterial baroreflex. Dietary restriction was defined as 40% reduction of dietary intake. Briefly, DR prolonged the life span of SP-SHRs and reduced the infarct size induced by MCAO. Dietary restriction also improved the function arterial baroreflex, decreased the release of proinflammatory cytokines, and reduced end-organ damage. The beneficial effect of DR on stroke was markedly attenuated by blunting arterial baroreflex. Lastly, the infarct area in sirt1 KO mice was significantly larger than in the wild-type mice. However, the beneficial effect of DR against ischemic injury was still apparent in sirt1 KO mice. Accordingly, arterial baroreflex, but not sirt1, is important in the protective effect of DR against stroke. PMID:23443169

Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow-up.

PubMed

Dalla Vecchia, Laura; Barbic, Franca; Galli, Andrea; Pisacreta, Massimo; Gornati, Rosella; Porretta, Tiziano; Porta, Alberto; Furlan, Raffaello

2013-06-15

Carotid surgery variably modifies carotid afferent innervation, thus affecting arterial baroreceptor sensitivity. Low arterial baroreflex sensitivity is a well-known independent risk factor for cardiovascular diseases. The aim of this study was to assess the 4-mo effects of carotid endarterectomy (CEA) on arterial baroreceptor sensitivity and cardiovascular autonomic profile in patients with unilateral carotid stenosis. We enrolled 20 patients (72 ± 8 yr) with unilateral >70% carotid stenosis. ECG, beat-by-beat blood pressure, and respiration were continuously recorded before and 126 ± 9 days after CEA, at rest and during a 75° head-up tilt. Both pharmacological (modified Oxford technique, BRS) and spontaneous (index α, spectral analysis) arterial baroreflex sensitivity were assessed. Cardiovascular autonomic profile was evaluated by plasma catecholamines and spectral indexes of cardiac sympathovagal modulation [low-frequency R-R interval (LFRR), low frequency-to high frequency ratio (LF/HF), high-frequency R-R interval (HFRR)] and sympathetic vasomotor control [low-frequency systolic arterial pressure (LFSAP)] obtained from heart rate and SAP variability. After CEA, both the index α and BRS were higher (P < 0.02) at rest. SAP variance decreased both at rest and during tilt (P < 0.02). Before surgery, tilt did not modify the autonomic profile compared with baseline. After CEA, tilt increased LF/HF and LFSAP and reduced HFRR compared with rest (P < 0.02). Four months after CEA was performed, arterial baroreflex sensitivity was enhanced. Accordingly, the patients' autonomic profile had shifted toward reduced cardiac and vascular sympathetic activation and enhanced cardiac vagal activity. The capability to increase cardiovascular sympathetic activation in response to orthostasis was restored. Baroreceptor sensitivity improvement might play an additional role in the more favorable outcome observed in patients after carotid surgery.

Baroreflex function: determinants in healthy subjects and disturbances in diabetes, obesity and metabolic syndrome.

PubMed

Skrapari, Ioanna; Tentolouris, Nicholas; Katsilambros, Nicholas

2006-08-01

Arterial baroreceptors play an important role in the short-term regulation of arterial pressure, by reflex chronotropic effect on the heart and by reflex regulation of sympathetic outflow. Baroreflex sensitivity (BRS) represents an index of arterial baroreceptors function. Several methods of measuring BRS are available nowadays. Different factors influence BRS in the healthy population, including sex, age, blood pressure, heart rate, body fatness, arterial stiffness, blood glucose and insulin levels, as well as physical activity. Baroreceptors dysfunction is evident in diseases such as coronary artery disease, heart failure, arterial hypertension, diabetes mellitus and obesity. The underlying mechanism of BRS attenuation in diabetes or obesity is not yet well known; however, there is increasing evidence that it is at least partly related to autonomic nervous system dysfunction and particularly to sympathetic overactivity that accompanies these diseases. Blunted BRS provides prognostic information for cardiovascular diseases and possibly for diabetes, while its' prognostic information for obesity is not yet established. This review deals with the mechanisms affecting baroreflex function, the newer techniques of BRS estimation and the most recent insights of baroreflex function in the healthy population and in various diseases with emphasis on diabetes and obesity. In addition, the clinical implication of a reduced BRS in these disorders is discussed.

Neural blockade during exercise augments central command's contribution to carotid baroreflex resetting

NASA Technical Reports Server (NTRS)

Querry, R. G.; Smith, S. A.; Stromstad, M.; Ide, K.; Raven, P. B.; Secher, N. H.

2001-01-01

This investigation was designed to determine central command's role on carotid baroreflex (CBR) resetting during exercise. Nine volunteer subjects performed static and rhythmic handgrip exercise at 30 and 40% maximal voluntary contraction (MVC), respectively, before and after partial axillary neural blockade. Stimulus-response curves were developed using the neck pressure-neck suction technique and a rapid pulse train protocol (+40 to -80 Torr). Regional anesthesia resulted in a significant reduction in MVC. Heart rate (HR) and ratings of perceived exertion (RPE) were used as indexes of central command and were elevated during exercise at control force intensity after induced muscle weakness. The CBR function curves were reset vertically with a minimal lateral shift during control exercise and exhibited a further parallel resetting during exercise with neural blockade. The operating point was progressively reset to coincide with the centering point of the CBR curve. These data suggest that central command was a primary mechanism in the resetting of the CBR during exercise. However, it appeared that central command modulated the carotid-cardiac reflex proportionately more than the carotid-vasomotor reflex.

Trait anxiety mimics age-related cardiovascular autonomic modulation in young adults.

PubMed

Sanchez-Gonzalez, M A; Guzik, P; May, R W; Koutnik, A P; Hughes, R; Muniz, S; Kabbaj, M; Fincham, F D

2015-04-01

Anxiety produces maladaptive cardiovascular changes and accelerates biological aging. We evaluated cardiovascular reactivity in young and middle-aged individuals with varying anxiety scores to test the hypothesis that anxiety mimics cardiovascular aging by influencing cardiovascular autonomic modulation. The State-Trait Anxiety Inventory was used to classify healthy young individuals (20-29 years) into high (YHA, n=22;10 men) and low (YLA, n=21;10 men) anxiety, and to identify middle-aged individuals (50-60 years) with low anxiety (MLA, n=22;11 men). Heart rate, blood pressure (BP) and their variability (HRV and BPV, respectively) and baroreflex function were analyzed from beat-to-beat finger BP and electrocardiogram recordings collected during 5-min baseline, 6-min speech task (ST) and 3-min post ST recovery. Analyses of covariance showed significant differences (P<0.05) at baseline for HRV, BPV and barorelfex, and low-frequency power of systolic BP variability (LFSBP) was lower, whereas baroreflex and high frequency (HF) normalized units were higher in the YLA compared with YHA and MLA groups. Compared with YLA, YHA and MLA displayed attenuated vagal withdraw response (HF) to ST. BP and LFSBP responses to ST in YHA and MLA were higher compared with the YLA group. These findings suggest that anxiety could be linked to cardiovascular aging as it attenuates cardiac reactivity and exaggerates vascular responses to stress.

Autonomic Cardiovascular Control and Executive Function in Chronic Hypotension.

PubMed

Duschek, Stefan; Hoffmann, Alexandra; Reyes Del Paso, Gustavo A; Ettinger, Ulrich

2017-06-01

Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained. The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output. Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance.

Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

NASA Technical Reports Server (NTRS)

Smith, S. A.; Querry, R. G.; Fadel, P. J.; Welch-O'Connor, R. M.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

2000-01-01

PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS: During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained neck suction and pressure were applied to counteract altered carotid sinus pressure during SN and PE administration, isolating the ABR response, the response range remained diminished (P < 0.05) in the HF population (24+/-3 beats x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1)) response ranges were similar. The arterial baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS: These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

Effect of low-dose scopolamine on autonomic control of the heart

NASA Technical Reports Server (NTRS)

Raeder, E. A.; Stys, A.; Cohen, R. J.

1997-01-01

Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

Effect of angiotension II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats

PubMed Central

Zhang, Dongze; Liu, Jinxu; Zheng, Hong; Tu, Huiyin; Muelleman, Robert L.; Li, Yu-Long

2016-01-01

Impairment of arterial baroreflex sensitivity is associated with mortality in patients with chronic heart failure (CHF). Elevation of plasma angiotension II (Ang II) contributes to arterial baroreflex dysfunction in CHF. A reduced number of voltage-gated sodium (Nav) channels in aortic baroreceptor neurons are involved in CHF-blunted arterial baroreflex. In this study, we investigated acute effect of Ang II on Nav currents in the aortic baroreceptor neuron and on arterial baroreflex in sham and coronary artery ligation-induced CHF rats. Using Ang II 125I radioimmunoassay, real-time RT-PCR and western blot, we found that Ang II levels, and mRNA and protein expression of angiotension II type 1 receptor (AT1R) in nodose ganglia (NG) from CHF rats were higher than that from sham rats. Local microinjection of Ang II (0.2 nmol) into the NG decreased the arterial baroreflex sensitivity in sham rats, whereas losartan (1 nmol, an AT1R antagonist) improved the arterial baroreflex sensitivity in CHF rats. Data from patch-clamp recording showed that Ang II (100 nM) acutely inhibited Nav currents in the aortic baroreceptor neurons from sham and CHF rats. In particular, inhibitory effect of Ang II on Nav currents in the aortic baroreceptor neurons was larger in CHF rats than that in sham rats. Losartan (1 μM) totally abolished the inhibitory effect of Ang II on Nav currents in sham and CHF aortic baroreceptor neurons. These results suggest that elevation of endogenous Ang II in the NG contributes to impairment of the arterial baroreflex function in CHF rats through inhibiting Nav channels. PMID:25827427

Heart rate and cardiovascular variability at high altitude.

PubMed

Bernardi, Luciano

2007-01-01

Primary effect of hypobaric hypoxia on the circulation is a direct vasodilatory effect on the peripheral circulation, which is normally prevented by a sympathetic-induced vasoconstriction. Most of the clinical methods for testing the baroreflex sensitivity only evaluate the cardiac-vagal branch of the baroreflex, but at altitude it is also of importance to test the vascular effects of the baroreflex. This is possible by directly measuring sympathetic efferent activity (by microneurography) or by directly stimulating the carotid baroreceptors (by the neck suction). By cyclical stimulation of the carotid baroreceptors, neck suction-synchronous reflex oscillations could be observed in a large number of signals, including RR interval, blood pressure, microcirculation, muscle sympathetic nerve activity. An increase in fluctuations at the same frequency of the stimulus was considered an evidence of the ability of the carotid baroreceptors to modulate a given physiological signal. The sinusoidal neck suction was set at 0.10 Hz (low-frequency stimulation), or to a frequency close to- but distinct from- the respiratory signal (0.20 Hz, high frequency stimulation, whereas respiration was fixed to 0.25 Hz). The method is noninvasive, without side effects connected to use of drugs, and evaluates both the response to the heart and to the blood pressure of the baroreflex. The altitude-induced sympathetic activation was evidenced in sea level natives by a decrease in RR interval, an increase in blood pressure and in the 0.1Hz components of cardiac and vascular signals. The arterial baroflex was active on RR interval and also in blood pressure, even during acute exposure to high altitude, thus indicating that it was counteracting and modulating the increase in sympathetic tone. Signs of exaggerated sympathetic activation were evident in subjects with severe acute mountain sickness, while successful therapy was associated with a restoration of autonomic modulation. Conversely, sympathetic activation was reduced( and baroflex enhanced) in himalayan high altitude natives. In conclusion, a comprehensive understanding of the mechanism taking place during the adaptation to high altitude requires a multisignal approach, also integrated with equipment designed to provide specific provocative tests, such as those necessary to measure the cardiorespiratory interactions.

A statistical note on the redundancy of nine standard baroreflex parameters

NASA Technical Reports Server (NTRS)

Ludwig, David A.; Convertino, Victor A.

1991-01-01

An accepted method for measuring the responsiveness of the carotid-cardiac baroreflex to arterial pressure changes is to artificially stimulate the baroreceptors in the neck with a pressurized neck chamber. Nine physiological responses to this type of stimulation are quantified and used as indicators of the baroreflex response function. Thirty male humans between the ages of 27 and 46 underwent the carotid-cardiac baroreflex test. The data for the nine response parameters were analyzed by principle component factor analysis. The results indicated that 92.5 percent of the total variance across all nine parameters could be explained in four dimensions. The first two dimensions reflected location points for R-R interval and carotid distending pressure, respectively. The third factor was composed of measures reflecting the gain (responsiveness) of the reflex. The fourth dimension was the ratio of baseline R-R interval to the maximal R-R interval response during simulated hypertension. The data suggest that the analysis of all nine baroreflex parameters is likely to be redundant and researchers should account for these redundancies either in their analyses or conclusions.

Interaction of semicircular canal stimulation with carotid baroreceptor reflex control of heart rate

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1998-01-01

The carotid-cardiac baroreflex contributes to the prediction of orthostatic tolerance; experimental attenuation of the reflex response leads to orthostatic hypotension in humans and animals. Anecdotal observations indicate that rotational head movements about the vertical axis of the body can also induce orthostatic bradycardia and hypotension through increased parasympathetic activity. We therefore measured the chronotropic response to carotid baroreceptor stimulation in 12 men during varying conditions of vestibulo-oculomotor stimulation to test the hypothesis that stimulation of the semicircular canals associated with head movements in the yaw plane inhibits cardioacceleration through a vagally mediated baroreflex. Carotid-cardiac baroreflex response was assessed by plotting R-R intervals (ms) at each of 8 neck pressure steps with their respective carotid distending pressures (mmHg). Calculated baroreflex gain (maximal slope of the stimulus-response relationship) was measured under 4 experimental conditions: 1) sinusoidal whole-body yaw rotation of the subject in the dark without visual fixation (combined vestibular-oculomotor stimulation); 2) yaw oscillation of the subject while tracking a small head-fixed light moving with the subject (vestibular stimulation without eye movements); 3) subject stationary while fixating on a small light oscillating in yaw at the same frequency, peak acceleration, and velocity as the chair (eye movements without vestibular stimulation); and 4) subject stationary in the dark (no eye or head motion). Head motion alone and with eye movement reduced baseline baroreflex responsiveness to the same stimulus by 30%. Inhibition of cardioacceleration during rotational head movements may have significant impact on functional performance in aerospace environments, particularly in high-performance aircraft pilots during high angular acceleration in aerial combat maneuvers or in astronauts upon return from spaceflight who already have attenuated baroreflex functions.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

PubMed Central

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-01-01

Abstract Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

PubMed

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-03-01

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

Central command differentially affects aortic and carotid sinus baroreflexes at the onset of spontaneous motor activity.

PubMed

Matsukawa, Kanji; Ishii, Kei; Idesako, Mitsuhiro; Ishida, Tomoko; Endo, Kana; Liang, Nan

2013-12-01

Our laboratory has recently demonstrated that central command provides selective inhibition of the cardiomotor component of aortic (AOR) baroreflex during exercise, preserving carotid sinus (CS) baroreflex. To further explore the differential effects of central command on the arterial baroreflexes, we surgically separated the AOR and CS baroreflex systems, to identify the input-output relationship of each baroreflex system using brief occlusion of the abdominal aorta in decerebrate cats. Baroreflex sensitivity for heart rate (HR) was estimated from the baroreflex ratio between the pressor and bradycardia responses during aortic occlusion and from the slope of the baroreflex curve between the changes in mean arterial blood pressure (ΔMAP) and ΔHR. Spontaneous motor activity accompanied the abrupt increases in HR and MAP. When aortic occlusion was given at the onset of spontaneous motor activity, the baroreflex ratio was blunted to 11-25% of the preexercise value in either intact or AOR baroreflex. The slope of the ΔMAP-ΔHR curve was similarly attenuated at the onset of spontaneous motor activity to 11-18% of the slope during the preexercise period. In contrast, in the CS baroreflex, the baroreflex ratio and curve slope were not significantly (P>0.05) altered by spontaneous motor activity. An upward shift of the baroreflex curve appeared at the onset of spontaneous motor activity, irrespective of the intact, AOR, and CS baroreflex conditions. Taken together, it is concluded that central command provides selective inhibition for the cardiomotor limb of the aortic baroreflex at the onset of exercise, which in turn contributes to an instantaneous increase in HR. © 2013.

Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation

PubMed Central

Rivera, Eileen; Clarke, Debbie A.; Baugham, Ila L.; Ocon, Anthony J.; Taneja, Indu; Terilli, Courtney; Medow, Marvin S.

2011-01-01

Increasing arterial blood pressure (AP) decreases ventilation, whereas decreasing AP increases ventilation in experimental animals. To determine whether a “ventilatory baroreflex” exists in humans, we studied 12 healthy subjects aged 18–26 yr. Subjects underwent baroreflex unloading and reloading using intravenous bolus sodium nitroprusside (SNP) followed by phenylephrine (“Oxford maneuver”) during the following “gas conditions:” room air, hypoxia (10% oxygen)-eucapnia, and 30% oxygen-hypercapnia to 55–60 Torr. Mean AP (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), expiratory minute ventilation (VE), respiratory rate (RR), and tidal volume were measured. After achieving a stable baseline for gas conditions, we performed the Oxford maneuver. VE increased from 8.8 ± 1.3 l/min in room air to 14.6 ± 0.8 l/min during hypoxia and to 20.1 ± 2.4 l/min during hypercapnia, primarily by increasing tidal volume. VE doubled during SNP. CO increased from 4.9 ± .3 l/min in room air to 6.1 ± .6 l/min during hypoxia and 6.4 ± .4 l/min during hypercapnia with decreased TPR. HR increased for hypoxia and hypercapnia. Sigmoidal ventilatory baroreflex curves of VE versus MAP were prepared for each subject and each gas condition. Averaged curves for a given gas condition were obtained by averaging fits over all subjects. There were no significant differences in the average fitted slopes for different gas conditions, although the operating point varied with gas conditions. We conclude that rapid baroreflex unloading during the Oxford maneuver is a potent ventilatory stimulus in healthy volunteers. Tidal volume is primarily increased. Ventilatory baroreflex sensitivity is unaffected by chemoreflex activation, although the operating point is shifted with hypoxia and hypercapnia. PMID:21317304

Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

NASA Technical Reports Server (NTRS)

Zhang, R.; Behbehani, K.; Crandall, C. G.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

2001-01-01

To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Stromstad, M.; Hansen, J.; Sander, M.; Horn, K.; Ogoh, S.; Smith, M. L.; Secher, N. H.; Raven, P. B.

2001-01-01

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.

PubMed

Fadel, P J; Stromstad, M; Hansen, J; Sander, M; Horn, K; Ogoh, S; Smith, M L; Secher, N H; Raven, P B

2001-06-01

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Fouda, Mohamed A.; El-gowilly, Sahar M.

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were takenmore » as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.« less

Baroreflex control of renal sympathetic nerve activity in early heart failure assessed by the sequence method

PubMed Central

Lataro, Renata Maria; Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar

2017-01-01

Key points The integrity of the baroreflex control of sympathetic activity in heart failure (HF) remains under debate.We proposed the use of the sequence method to assess the baroreflex control of renal sympathetic nerve activity (RSNA).The sequence method assesses the spontaneous arterial pressure (AP) fluctuations and their related changes in heart rate (or other efferent responses), providing the sensitivity and the effectiveness of the baroreflex. Effectiveness refers to the fraction of spontaneous AP changes that elicits baroreflex‐mediated variations in the efferent response.Using three different approaches, we showed that the baroreflex sensitivity between AP and RSNA is not altered in early HF rats. However, the sequence method provided evidence that the effectiveness of baroreflex in changing RSNA in response to AP changes is markedly decreased in HF.The results help us better understand the baroreflex control of the sympathetic nerve activity. Abstract In heart failure (HF), the reflex control of the heart rate is known to be markedly impaired; however, the baroreceptor control of the sympathetic drive remains under debate. Applying the sequence method to a series of arterial pressure (AP) and renal sympathetic nerve activity (RSNA), we demonstrated a clear dysfunction in the baroreflex control of sympathetic activity in rats with early HF. We analysed the baroreflex control of the sympathetic drive using three different approaches: AP vs. RSNA curve, cross‐spectral analysis and sequence method between AP and RSNA. The sequence method also provides the baroreflex effectiveness index (BEI), which represents the percentage of AP ramps that actually produce a reflex response. The methods were applied to control rats and rats with HF induced by myocardial infarction. None of the methods employed to assess the sympathetic baroreflex gain were able to detect any differences between the control and the HF group. However, rats with HF exhibited a lower BEI compared to the controls. Moreover, an optimum delay of 1 beat was observed, i.e. 1 beat is required for the RSNA to respond after AP changing, which corroborates with the findings related to the timing between these two variables. For delay 1, the BEI of the controls was 0.45 ± 0.03, whereas the BEI of rats with HF was 0.29 ± 0.09 (P < 0.05). These data demonstrate that while the gain of the baroreflex is not affected in early HF, its effectiveness is markedly decreased. The analysis of the spontaneous changes in AP and RSNA using the sequence method provides novel insights into arterial baroreceptor reflex function. PMID:28261799

Muscle metaboreflex contribution to cardiovascular regulation during dynamic exercise in microgravity: insights from mission STS-107 of the space shuttle Columbia.

PubMed

Iellamo, Ferdinando; Di Rienzo, Marco; Lucini, Daniela; Legramante, Jacopo M; Pizzinelli, Paolo; Castiglioni, Paolo; Pigozzi, Fabio; Pagani, Massimo; Parati, Gianfranco

2006-05-01

One of the most important features of prolonged weightlessness is a progressive impairment of muscular function with a consequent decrease in exercise capacity. We tested the hypothesis that the impairment in musculo-skeletal function that occurs in microgravity results in a potentiation of the muscle metaboreflex mechanism and also affects baroreflex modulation of heart rate (HR) during exercise. Four astronauts participating in the 16 day Columbia shuttle mission (STS-107) were studied 72-71 days before launch and on days 12-13 in-flight. The protocol consisted of 6 min bicycle exercise at 50% of individual V(o2,max) followed by 4 min of postexercise leg circulatory occlusion (PECO). At rest, systolic (S) and diastolic (D) blood pressure (BP), R-R interval and baroreflex sensitivity (BRS) did not differ significantly between pre- and in-flight measurements. Both pre- and in-flight, SBP increased and R-R interval and BRS decreased during exercise, whereas DBP did not change. During PECO preflight, SBP and DBP were higher than at rest, whereas R-R interval and BRS recovered to resting levels. During PECO in-flight, SBP and DBP were significantly higher whereas R-R interval and BRS remained significantly lower than at rest. The part of the SBP response (delta) that was maintained by PECO was significantly greater during spaceflight than before (34.5 +/- 8.8 versus 13.8 +/- 11.9 mmHg, P = 0.03). The tachycardic response to PECO was also significantly greater during spaceflight than preflight (-141.5 +/- 25.2 versus - 90.5 +/- 33.3 ms, P = 0.02). This study suggests that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.

Changes in plasma volume and baroreflex function following resistance exercise

NASA Technical Reports Server (NTRS)

Ploutz, L. L.; Tatro, D. L.; Dudley, G. A.; Convertino, V. A.

1993-01-01

The dynamics of change in plasma volume (PV) and baroreflex responses have been reported over 24 h immediately following maximal cycle exercise. The purpose of this study was to determine if PV and baroreflex showed similar changes for 24 h after resistance exercise. Eight men were studied on 2 test days, 1 week apart. On 1 day, per cent change (% delta) in PV was estimated at 0,3, and 6 h after resistance exercise using haematocrit and haemoglobin. Baseline PV was measured 24 h after exercise using Evans blue dye. The carotid baroreceptor-cardiac reflex response was measured before, and 3, 6, 9, 12, and 24 h post-exercise. Each subject performed six sets of the bench press and leg press with 10 repetitions per set with a load that induced failure within each set. On a control day, the protocol was used without exercise. Plasma volume did not change during the control day. There was a 20% decrease in PV immediately post-exercise; the recovery of the PV was rapid and complete within 3 h. PV was 20% greater 24 h post-exercise than on the control day. There were no differences in any of the baroreflex measurements. Therefore, it is suggested that PV shifts may occur without altering baroreflex sensitivity.

Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

PubMed Central

Sirvente, Raquel A.; Irigoyen, Maria C.; Souza, Leandro E.; Mostarda, Cristiano; La Fuente, Raquel N.; Candido, Georgia O.; Souza, Pamella R. M.; Medeiros, Alessandra; Mady, Charles; Salemi, Vera M. C.

2014-01-01

Background Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. Methods and Results We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. Conclusions Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease. PMID:24828834

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease.

PubMed

Sárközi, Adrienn; Cseh, Domonkos; Gerlei, Zsuzsanna; Kollai, Márk

2018-02-01

Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS. We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery. Integrated BRS was reduced in patients [7.00 (5.80-9.25) vs. 11.1 (8.50-14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54 ± 1.20 vs. 4.48 ± 1.43 ms/10 -3 ). FMD was higher in patients (9.81 ± 3.77 vs. 5.59 ± 1.36%). FMD and neural BRS were directly related in controls (r = 0.62), but inversely related in patients (r = -0.49). Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.

Role of adenosine A{sub 2A} receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; El-gowilly, Sahar M.; Fouda, Mohamed A.

Baroreflex dysfunction contributes to increased cardiovascular risk in cigarette smokers. Given the importance of adenosinergic pathways in baroreflex control, the hypothesis was tested that defective central adenosinergic modulation of cardiac autonomic activity mediates the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1-16 {mu}g/kg) of phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious rats; slopes of the curves were taken as measures of baroreflex sensitivity (BRS). Nicotine (25 and 100 {mu}g/kg i.v.) dose-dependently reduced BRS{sub SNP} in contrast to no effect on BRS{submore » PE}. BRS{sub SNP} was also attenuated after intracisternal (i.c.) administration of nicotine. Similar reductions in BRS{sub SNP} were observed in rats pretreated with atropine or propranolol. The combined treatment with nicotine and atropine produced additive inhibitory effects on BRS, an effect that was not demonstrated upon concurrent exposure to nicotine and propranolol. BRS{sub SNP} was reduced in preparations treated with i.c. 8-phenyltheophylline (8-PT, nonselective adenosine receptor antagonist), 8-(3-Chlorostyryl) caffeine (CSC, A{sub 2A} antagonist), or VUF5574 (A{sub 3} antagonist). In contrast, BRS{sub SNP} was preserved after blockade of A{sub 1} (DPCPX) or A{sub 2B} (alloxazine) receptors or inhibition of adenosine uptake by dipyridamole. CSC or 8-PT abrogated the BRS{sub SNP} depressant effect of nicotine whereas other adenosinergic antagonists were without effect. Together, nicotine preferentially impairs reflex tachycardia via disruption of adenosine A{sub 2A} receptor-mediated facilitation of reflex cardiac sympathoexcitation. Clinically, the attenuation by nicotine of compensatory sympathoexcitation may be detrimental in conditions such as hypothalamic defense response, posture changes, and ventricular rhythms. - Research Highlights: > The role of central adenosinergic sites in the nicotine-baroreflex interaction was investigated. > Inhibition of reflex sympathoinhibition mediates the BRS depressant action of nicotine. > Nicotine preferentially impairs reflex tachycardia via disruption of adenosine A{sub 2A} signaling. > The attenuation by nicotine of reflex sympathetic activity is clinically important.« less

Systemic and Renal-Specific Sympathoinhibition in Obesity Hypertension

PubMed Central

Lohmeier, Thomas E.; Iliescu, Radu; Liu, Boshen; Henegar, Jeffrey R.; Maric-Bilkan, Christine; Irwin, Eric D.

2012-01-01

Chronic pressure-mediated baroreflex activation suppresses renal sympathetic nerve activity. Recent observations indicate that chronic electrical activation of the carotid baroreflex produces sustained reductions in global sympathetic activity and arterial pressure. Thus, we investigated the effects of global and renal specific suppression of sympathetic activity in dogs with sympathetically-mediated, obesity-induced hypertension by comparing the cardiovascular, renal, and neurohormonal responses to chronic baroreflex activation and bilateral surgical renal denervation. After control measurements, the diet was supplemented with beef fat while sodium intake was held constant. After 4 weeks on the high-fat, when body weight had increased ~a 50%, fat intake was reduced to a level that maintained this body weight. This weight increase was associated with an increase in mean arterial pressure from 100±2 to 117±3 mm Hg and heart rate from 86±3 to 130±4 bpm. The hypertension was associated with a marked increase in cumulative sodium balance despite ~ a 35% increase in GFR. The importance of increased tubular reabsorption to sodium retention was further reflected by ~ a 35% decrease in fractional sodium excretion. Subsequently, both chronic baroreflex activation (7 days) and renal denervation decreased plasma renin activity and abolished the hypertension. However, baroreflex activation also suppressed systemic sympathetic activity and tachycardia and reduced glomerular hyperfiltration while increasing fractional sodium excretion. In contrast, GFR increased further after renal denervation. Thus, by improving autonomic control of cardiac function and diminishing glomerular hyperfiltration, suppression of global sympathetic activity by baroreflex activation may have beneficial effects in obesity beyond simply attenuating hypertension. PMID:22184321

Comparison of the effect of valsartan and lisinopril on autonomic nervous system activity in chronic heart failure.

PubMed

De Tommasi, Elisabetta; Iacoviello, Massimo; Romito, Roberta; Ceconi, Claudio; Guida, Pietro; Massari, Francesco; Francolini, Gloria; Bertocchi, Federico; Ferrari, Roberto; Rizzon, Paolo; Pitzalis, Maria Vittoria

2003-11-01

In chronic heart failure (CHF), the derangement of autonomic nervous system activity has a deep impact on the progression of the disease. It has been demonstrated that modulation of the renin-angiotensin aldosterone system (RAAS) increases autonomic control of heart rate and reduces adrenergic activity. We sought to evaluate, in CHF, the different effects of an ACE inhibitor (lisinopril) and of an AT1 receptor antagonist (valsartan) on heart rate variability, baroreflex sensitivity and norepinephrine plasma levels. Ninety patients (61 +/- 10 years, 2.3 +/- 0.5, New York Heart Association class) with CHF and left ventricular ejection fraction <40% were randomly assigned in a double-blind fashion to receive lisinopril (uptitrated to 20 mg/d) or valsartan (uptitrated to 160 mg/d) therapy for 16 weeks. Heart rate variability (evaluated by measuring standard deviation of normal R-R intervals on 24-hour ECG recordings), spontaneous baroreflex sensitivity and aldosterone and norepinephrine plasma levels were assessed before and after drug therapy. There were no significant differences between valsartan and lisinopril in their effects on left ventricular function, arterial pressure, aldosterone plasma levels and autonomic control of heart rate. Both lisinopril and valsartan significantly reduced plasma norepinephrine levels, but the reduction induced by valsartan was significantly greater than that observed for lisinopril (27% vs 6%, P <.05). This study shows a comparable effect of ACE inhibition (lisinopril) and of AT1 receptor antagonism (valsartan) on cardiac vagal control of heart rate, whereas valsartan has shown a more effective modulation of sympathetic activity measured by plasma norepinephrine levels.

Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine

NASA Technical Reports Server (NTRS)

Rudas, L.; Crossman, A. A.; Morillo, C. A.; Halliwill, J. R.; Tahvanainen, K. U.; Kuusela, T. A.; Eckberg, D. L.

1999-01-01

We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

Hyperthermia modifies muscle metaboreceptor and baroreceptor modulation of heat loss in humans.

PubMed

Binder, Konrad; Lynn, Aaron G; Gagnon, Daniel; Kondo, Narihiko; Kenny, Glen P

2012-02-15

The relative influence of muscle metabo- and baroreflex activity on heat loss responses during post-isometric handgrip (IHG) exercise ischemia remains unknown, particularly under heat stress. Therefore, we examined the separate and integrated influences of metabo- and baroreceptor-mediated reflex activity on sweat rate and cutaneous vascular conductance (CVC) under increasing levels of hyperthermia. Twelve men performed 1 min of IHG exercise at 60% of maximal voluntary contraction followed by 2 min of ischemia with simultaneous application of lower body positive pressure (LBPP, +40 mmHg), lower body negative pressure (LBNP, -20 mmHg), or no pressure (control) under no heat stress. On separate days, trials were repeated under heat stress conditions of 0.6°C (moderate heat stress) and 1.4°C (high heat stress) increase in esophageal temperature. For all conditions, mean arterial pressure was greater with LBPP and lower with LBNP than control during ischemia (all P ≤ 0.05). No differences in sweat rate were observed between pressure conditions, regardless of the level of hyperthermia (P > 0.05). Under moderate heat stress, no differences in CVC were observed between pressure conditions. However, under high heat stress, LBNP significantly reduced CVC by 21 ± 4% (P ≤ 0.05) and LBPP significantly elevated CVC by 14 ± 5% (P ≤ 0.05) relative to control. These results show that sweating during post-IHG exercise ischemia is activated by metaboreflex stimulation, and not by baroreflexes. In contrast, our results suggest that baroreflexes can influence the metaboreflex modulation of CVC, but only at greater levels of hyperthermia.

The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

PubMed

Brasil, Girlandia Alexandre; Silva-Cutini, Mirian de Almeida; Moraes, Flávia de Souza Andrade; Pereira, Thiago de Melo Costa; Vasquez, Elisardo Corral; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Lima, Ewelyne Miranda; Biancardi, Vinícia Campana; Maia, June Ferreira; de Andrade, Tadeu Uggere

We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP 50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP 50 , the lower plateau, and HR range. In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal Neurocirculatory Control During Exercise in Humans with Chronic Renal Failure

PubMed Central

Park, Jeanie; Middlekauff, Holly R.

2014-01-01

Abnormal neurocirculatory control during exercise is one important mechanism leading to exercise intolerance in patients with both end-stage renal disease (ESRD) and earlier stages of chronic kidney disease (CKD). This review will provide an overview of mechanisms underlying abnormal neurocirculatory and hemodynamic responses to exercise in patients with kidney disease. Recent studies have shown that ESRD and CKD patients have an exaggerated increase in blood pressure (BP) during both isometric and rhythmic exercise. Subsequent studies examining the role of the exercise pressor reflex in the augmented pressor response revealed that muscle sympathetic nerve activity (MSNA) was not augmented during exercise in these patients, and metaboreflex-mediated increases in MSNA were blunted, while mechanoreflex-mediated increases were preserved under basal conditions. However, normalizing the augmented BP response during exercise via infusion of nitroprusside (NTP), and thereby equalizing baroreflex-mediated suppression of MSNA, an important modulator of the final hemodynamic response to exercise, revealed that CKD patients had an exaggerated increase in MSNA during isometric and rhythmic exercise. In addition, mechanoreflex-mediated control was augmented, and metaboreceptor blunting was no longer apparent in CKD patients with baroreflex normalization. Factors leading to mechanoreceptor sensitization, and other mechanisms underlying the exaggerated exercise pressor response, such as impaired functional sympatholysis, should be investigated in future studies. PMID:25458430

Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

PubMed Central

Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

2013-01-01

Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

Baroreflex Function in Rats after Simulated Microgravity

NASA Technical Reports Server (NTRS)

Hasser, Eileen M.

1997-01-01

Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

Malignant vagotonia due to selective baroreflex failure

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Black, B. K.; Costa, F.; Ertl, A. C.; Furlan, R.; Biaggioni, I.; Robertson, D.

1997-01-01

Baroreflex failure is characterized by dramatic fluctuations of sympathetic activity and paroxysms of hypertension and tachycardia. In contrast, unopposed parasympathetic activity has not been described in patients with baroreflex failure because of concurrent parasympathetic denervation of the heart. We describe the unusual case of a patient with baroreflex failure in a setting of preserved parasympathetic control of HR manifesting episodes of severe bradycardia and asystole. Thus, parasympathetic control of the HR may be intact in occasional patients with baroreflex failure. Patients with this selective baroreflex failure require a unique therapeutic strategy for the control of disease manifestations.

MRI/DTI of the Brain Stem Reveals Reversible and Irreversible Disruption of the Baroreflex Neural Circuits: Clinical Implications

PubMed Central

Su, Chia-Hao; Tsai, Ching-Yi; Chang, Alice Y.W.; Chan, Julie Y.H.; Chan, Samuel H.H.

2016-01-01

Baroreflex is the physiological mechanism for the maintenance of blood pressure and heart rate. Impairment of baroreflex is not a disease per se. However, depending on severity, the eventuality of baroreflex dysfunction varies from inconvenience in daily existence to curtailment of mobility to death. Despite universal acceptance, neuronal traffic within the contemporary neural circuits during the execution of baroreflex has never been visualized. By enhancing signal detection and fine-tuning the scanning parameters, we have successfully implemented tractographic analysis of the medulla oblongata in mice that allowed for visualization of connectivity between key brain stem nuclei in the baroreflex circuits. When viewed in conjunction with radiotelemetric analysis of the baroreflex, we found that under pathophysiological conditions when the disrupted connectivity between key nuclei in the baroreflex circuits was reversible, the associated disease condition (e.g. neurogenic hypertension) was amenable to remedial measures. Nevertheless, fatality ensues under pathological conditions (e.g. hepatic encephalopathy) when the connectivity between key substrates in the baroreflex circuits was irreversibly severed. MRI/DTI also prompted partial re-wiring of the contemporary circuit for baroreflex-mediated sympathetic vasomotor tone, and unearthed an explanation for the time lapse between brain death and the inevitable asystole signifying cardiac death that follows. PMID:27162554

MRI/DTI of the Brain Stem Reveals Reversible and Irreversible Disruption of the Baroreflex Neural Circuits: Clinical Implications.

PubMed

Su, Chia-Hao; Tsai, Ching-Yi; Chang, Alice Y W; Chan, Julie Y H; Chan, Samuel H H

2016-01-01

Baroreflex is the physiological mechanism for the maintenance of blood pressure and heart rate. Impairment of baroreflex is not a disease per se. However, depending on severity, the eventuality of baroreflex dysfunction varies from inconvenience in daily existence to curtailment of mobility to death. Despite universal acceptance, neuronal traffic within the contemporary neural circuits during the execution of baroreflex has never been visualized. By enhancing signal detection and fine-tuning the scanning parameters, we have successfully implemented tractographic analysis of the medulla oblongata in mice that allowed for visualization of connectivity between key brain stem nuclei in the baroreflex circuits. When viewed in conjunction with radiotelemetric analysis of the baroreflex, we found that under pathophysiological conditions when the disrupted connectivity between key nuclei in the baroreflex circuits was reversible, the associated disease condition (e.g. neurogenic hypertension) was amenable to remedial measures. Nevertheless, fatality ensues under pathological conditions (e.g. hepatic encephalopathy) when the connectivity between key substrates in the baroreflex circuits was irreversibly severed. MRI/DTI also prompted partial re-wiring of the contemporary circuit for baroreflex-mediated sympathetic vasomotor tone, and unearthed an explanation for the time lapse between brain death and the inevitable asystole signifying cardiac death that follows.

Abnormal sympathetic nerve activity in women exposed to cigarette smoke: a potential mechanism to explain increased cardiac risk.

PubMed

Middlekauff, Holly R; Park, Jeanie; Agrawal, Harsh; Gornbein, Jeffrey A

2013-11-15

In women, cardiac deaths attributable to tobacco exposure have reached the same high levels as men. Normally, sympathetic nerve activity (SNA) fluctuates according to the menstrual phase, but in habitual smokers, SNA levels remain constant. Our purpose is to extend these observations to other groups of women exposed to tobacco smoke and to explore potential mechanisms. We hypothesize that women exposed to secondhand smoke, but not former smokers, have nonfluctuating SNA compared with never smokers, and that impaired baroreflex suppression of SNA, and/or heightened central SNA responses, underlie this nonfluctuating SNA. We also hypothesize that female smokers have impaired nocturnal blood pressure dipping, normally mediated by modulation of SNA. In 49 females (19 never, 12 current, 9 former, 9 passive smokers), SNA was recorded (microneurography) during high- and low-hormone ovarian phases at rest, during pharmacological baroreflex testing, and during the cold pressor test (CPT). Twenty-four hour blood pressure (BP) monitoring was performed. Current and passive smokers, but not former smokers, had a nonfluctuating pattern of SNA, unlike never smokers in whom SNA varied with the menstrual phase. Baroreflex control of SNA was significantly blunted in current smokers, independent of menstrual phase. In passive smokers, SNA response to CPT was markedly increased. Nondipping was unexpectedly high in all groups. SNA does not vary during the menstrual cycle in active and passive smokers, unlike never and former smokers. Baroreflex control of SNA is blunted in current smokers, whereas SNA response to CPT is heightened in passive smokers. Smoking cessation is associated with return of the altered SNA pattern to normal.

Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass.

PubMed

Hildebrandt, Drew A; Irwin, Eric D; Lohmeier, Thomas E

2016-12-01

Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated for therapy in patients with resistant hypertension. However, patients with significant impairment of renal function have been largely excluded from clinical trials. Thus, there is little information on blood pressure and renal responses to baroreflex activation in subjects with advanced chronic kidney disease, which is common in resistant hypertension. Changes in arterial pressure and glomerular filtration rate were determined in 5 dogs after combined unilateral nephrectomy and surgical excision of the poles of the remaining kidney to produce ≈70% reduction in renal mass. After control measurements, sodium intake was increased from ≈45 to 450 mol/d. While maintained on high salt, animals experienced increases in mean arterial pressure from 102±4 to 121±6 mm Hg and glomerular filtration rate from 40±2 to 45±2 mL/min. During 7 days of baroreflex activation, the hypertension induced by high salt was abolished (103±6 mm Hg) along with striking suppression of plasma norepinephrine concentration from 139±21 to 81±9 pg/mL, but despite pronounced blood pressure lowering, there were no significant changes in glomerular filtration rate (43±2 mL/min). All variables returned to prestimulation values during a recovery period. These findings indicate that after appreciable nephron loss, chronic suppression of central sympathetic outflow by baroreflex activation abolishes hypertension induced by high salt intake. The sustained antihypertensive effects of baroreflex activation occur without significantly compromising glomerular filtration rate in remnant nephrons. © 2016 American Heart Association, Inc.

Sustained acute voltage-dependent blood pressure decrease with prolonged carotid baroreflex activation in therapy-resistant hypertension.

PubMed

Alnima, Teba; Scheffers, Ingrid; De Leeuw, Peter W; Winkens, Bjorn; Jongen-Vancraybex, Heidi; Tordoir, Jan H M; Schmidli, Jürg; Mohaupt, Markus G; Allemann, Yves; Kroon, Abraham A

2012-08-01

Chronic carotid baroreflex stimulation (Rheos system) has been shown to effectively reduce blood pressure in patients with resistant hypertension. Upon acute stimulation blood pressure also falls as a function of voltage. the aim of this study is to evaluate whether this voltage-dependent blood pressure decrease is preserved after long-term carotid baroreflex stimulation. Forty-five patients implanted with Rheos underwent a voltage response test (VRT) before the start of carotid baroreflex activation (1m), as well as after 4 (4m) and 13 months (13 m) of device implantation. After switching off the device for 10 min (0 V), we started the VRT by increasing voltage from 1 to 6 V, by 1-V steps every 5 min. Blood pressure and heart rate were measured at the end of every step. At 1m, mean blood pressure was 178/101 mmHg at 0 V and fell to 142/83 mmHg at 6 V. Heart rate fell from 75 to 65 beats/min. At 4m and 13 m mean blood pressure was significantly lower compared to 1m when VRT started at 0 V (170/96 and 161/93 mmHg, respectively). However, pattern of blood pressure decrease during VRT was comparable with this at 1m. Maximum SBP reduction during VRT did not change with long-term therapy. Acute voltage-dependent blood pressure and heart rate decrease with electrical baroreflex stimulation is preserved after at least 1 year of continuous activation in patients with resistant hypertension. This indicates that response adaptation and nerve fatigue are very unlikely in long-term carotid baroreflex activation.

Interaction of central venous pressure, intramuscular pressure, and carotid baroreflex function

NASA Technical Reports Server (NTRS)

Shi, X.; Foresman, B. H.; Raven, P. B.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

Seven healthy volunteer men participated in an experiment involving lower body positive pressure (LBPP) of 30 Torr and acute volume expansions of 5-6% (VE-I) and 9-10% (VE-II) of their total blood volume (TBV) to differentiate the effect of increased intramuscular pressure and central venous pressure (CVP) on the maximal gain (Gmax) of the carotid baroreflex. During each experimental condition, the heart rate (HR), mean arterial pressure (MAP; intraradial artery or Finapres), and CVP (at the 3rd-4th intercostal space) were monitored continuously. Gmax was derived from the logistic modeling of the HR and MAP responses to ramped changes in carotid sinus transmural pressure using a protocol of pulsatile changes in neck chamber pressure from +40 to -65 Torr. The increase in CVP during +30-Torr LBPP was 1.5 mmHg (P < 0.05) and was similar to that observed during VE-I (1.7 mmHg, P > 0.05). The Gmax of the carotid baroreflex of HR and MAP was significantly decreased during LBPP by -0.145 +/- 0.039 beats x min(-1) x mmHg(-1) (38%) and -0.071 +/- 0.013 mmHg/mmHg (25%), respectively; however, VE-I did not affect Gmax. During VE-II, CVP was significantly greater than that elicited by LBPP, and the Gmax of the carotid baroreflex of the HR and MAP responses was significantly reduced. We conclude that carotid baroreflex responsiveness was selectively inhibited by increasing intramuscular pressure, possibly resulting in an activation of the intramuscular mechanoreceptors during LBPP. Furthermore, it would appear that the inhibition of the carotid baroreflex, via cardiopulmonary baroreceptor loading (increased CVP), occurred when a threshold pressure (CVP) was achieved.

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study.

PubMed

Sykora, Marek; Czosnyka, Marek; Liu, Xiuyun; Donnelly, Joseph; Nasr, Nathalie; Diedler, Jennifer; Okoroafor, Francois; Hutchinson, Peter; Menon, David; Smielewski, Peter

2016-06-01

Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. Retrospective analysis of a prospective database. Neurocritical care unit in a university hospital. Sedated patients with severe traumatic brain injury. Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p < 0.001) were individually associated with mortality, independently of age, admission Glasgow Coma Scale, intracranial pressure, pressure reactivity index, or cerebral perfusion pressure. Baroreflex sensitivity showed no correlation with intracranial pressure or cerebral perfusion pressure; the correlation with pressure reactivity index was strong in older patients (age, > 60 yr). The relative power of high frequency correlated significantly with intracranial pressure and cerebral perfusion pressure, but not with pressure reactivity index. The relative power of low frequency correlated significantly with pressure reactivity index. Autonomic impairment, as measured by heart rate variability and baroreflex sensitivity, is significantly associated with increased mortality after traumatic brain injury. These effects, though partially interlinked, seem to be independent of age, trauma severity, intracranial pressure, or autoregulatory status, and thus represent a discrete phenomenon in the pathophysiology of traumatic brain injury. Continuous measurements of heart rate variability and baroreflex sensitivity in the neuromonitoring setting of severe traumatic brain injury may carry novel pathophysiological and predictive information.

SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

PubMed Central

Hatcher, Jeffrey; Gu, He; Cheng, Zixi (Jack)

2016-01-01

Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2 ∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2 ∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID:26823951

Chronic Sleep Restriction during Pregnancy - Repercussion on Cardiovascular and Renal Functioning of Male Offspring

PubMed Central

Lima, Ingrid L. B.; Rodrigues, Aline F. A. C.; Bergamaschi, Cássia T.; Campos, Ruy R.; Hirata, Aparecida E.; Tufik, Sergio; Xylaras, Beatriz D. P.; Visniauskas, Bruna; Chagas, Jair R.; Gomes, Guiomar N.

2014-01-01

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi – tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127±2.6 (19); OCSR: 144±2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: −2.6±0.15 (9); OCRS: −1.6±0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4±15 (18); OSR: 60.2±3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4±0.2 (10); OCSR: 7.4±0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring. PMID:25405471

Chronic sleep restriction during pregnancy--repercussion on cardiovascular and renal functioning of male offspring.

PubMed

Lima, Ingrid L B; Rodrigues, Aline F A C; Bergamaschi, Cássia T; Campos, Ruy R; Hirata, Aparecida E; Tufik, Sergio; Xylaras, Beatriz D P; Visniauskas, Bruna; Chagas, Jair R; Gomes, Guiomar N

2014-01-01

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi - tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127 ± 2.6 (19); OCSR: 144 ± 2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: -2.6 ± 0.15 (9); OCRS: -1.6 ± 0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4 ± 15 (18); OSR: 60.2 ± 3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4 ± 0.2 (10); OCSR: 7.4 ± 0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring.

Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia

NASA Technical Reports Server (NTRS)

Ketch, Terry; Biaggioni, Italo; Robertson, RoseMarie; Robertson, David

2002-01-01

BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.

Baroreflex activation therapy in patients with prior renal denervation.

PubMed

Wallbach, Manuel; Halbach, Marcel; Reuter, Hannes; Passauer, Jens; Lüders, Stephan; Böhning, Enrico; Zenker, Dieter; Müller, Gerhard A; Wachter, Rolf; Koziolek, Michael J

2016-08-01

Both baroreflex activation therapy (BAT) and renal denervation modulate sympathetic activity. The aim of this study was to systematically investigate whether additive modulation of autonomic nervous system by BAT lowers blood pressure (BP) in patients who still suffer from uncontrolled resistant hypertension despite prior renal denervation. From 2012 to January 2015, patients treated with BAT for uncontrolled resistant hypertension, who prior received renal denervation were consecutively analyzed in four German centers for hypertension. Analyses of office BP, 24-h ambulatory BP, central hemodynamics, parameters of renal function were performed. A total of 28 patients, who underwent renal denervation at least 5 months before and still suffer from uncontrolled BP, were subsequently treated with BAT. The office SBP decreased from 182 ± 28 to 163 ± 27 mmHg (P < 0.01) with a responder rate of 68% (office SBP reduction ≥10 mmHg) at month 6, whereas the number of prescribed antihypertensive drug classes remained unchanged (6.2 ± 1.5 vs. 6.0 ± 1.7, P = 0.30). Serum creatinine, estimated glomerular filtration rate and cystatin C remained stable (P = 1.00, P = 0.41 and P = 0.22, respectively), whereas albuminuria was significantly reduced by a median of -29% (P = 0.02). Central SBP (-15 ± 24 mmHg, P = 0.047) and end systolic pressure (-14 ± 20 mmHg, P = 0.03) were significantly reduced. The present data demonstrate that BAT may exert BP-lowering as well as antiproteinuric effects in patients with prior renal denervation. However, precise evaluation of BAT effects in patients with prior renal denervation will need randomized controlled trials using sham procedures.

Effect of sex and ovarian hormones on carotid baroreflex resetting and function during dynamic exercise in humans

PubMed Central

Kim, Areum; Deo, Shekhar H.; Fisher, James P.

2012-01-01

To date, no studies have examined whether there are either sex- or ovarian hormone-related alterations in arterial baroreflex resetting and function during dynamic exercise. Thus we studied 16 young men and 18 young women at rest and during leg cycling at 50% heart rate (HR) reserve. In addition, 10 women were studied at three different phases of the menstrual cycle. Five-second pulses of neck pressure (NP) and neck suction (NS) from +40 to −80 Torr were applied to determine full carotid baroreflex (CBR) stimulus response curves. An upward and rightward resetting of the CBR function curve was observed during exercise in all groups with a similar magnitude of CBR resetting for mean arterial pressure (MAP) and HR between sexes (P > 0.05) and at different phases of the menstrual cycle (P > 0.05). For CBR control of MAP, women exhibited augmented pressor responses to NP at rest and exercise during mid-luteal compared with early and late follicular phases. For CBR control of HR, there was a greater bradycardic response to NS in women across all menstrual cycle phases with the operating point (OP) located further away from centering point (CP) on the CBR-HR curve during rest (OP-CP; in mmHg: −13 ± 3 women vs. −3 ± 3 men; P < 0.05) and exercise (in mmHg: −31 ± 2 women vs. −15 ± 3 men; P < 0.05). Collectively, these findings suggest that sex and fluctuations in ovarian hormones do not influence exercise resetting of the baroreflex. However, women exhibited greater CBR control of HR during exercise, specifically against acute hypertension, an effect that was present throughout the menstrual cycle. PMID:22267388

Short-term administration of progesterone and estradiol independently alter carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women.

PubMed

Brunt, Vienna E; Miner, Jennifer A; Kaplan, Paul F; Halliwill, John R; Strycker, Lisa A; Minson, Christopher T

2013-10-01

The individual effects of estrogen and progesterone on baroreflex function remain poorly understood. We sought to determine how estradiol (E2) and progesterone (P4) independently alter the carotid-cardiac and carotid-vasomotor baroreflexes in young women by using a hormone suppression and exogenous add-back design. Thirty-two young women were divided into two groups and studied under three conditions: 1) after 4 days of endogenous hormone suppression with a gonadotropin releasing hormone antagonist (control condition), 2) after continued suppression and 3 to 4 days of supplementation with either 200 mg/day oral progesterone (N = 16) or 0.1 to 0.2 mg/day transdermal 17β-estradiol (N = 16), and 3) after continued suppression and 3 to 4 days of supplementation with both hormones. Changes in heart rate (HR), mean arterial pressure (MAP), and femoral vascular conductance (FVC) were measured in response to 5 s of +50 mmHg external neck pressure to unload the carotid baroreceptors. Significant hormone effects on the change in HR, MAP, and FVC from baseline at the onset of neck pressure were determined using mixed model covariate analyses accounting for P4 and E2 plasma concentrations. Neither P4 (P = 0.95) nor E2 (P = 0.95) affected the HR response to neck pressure. Higher P4 concentrations were associated with an attenuated fall in FVC (P = 0.01), whereas higher E2 concentrations were associated with an augmented fall in FVC (P = 0.02). Higher E2 was also associated with an augmented rise in MAP (P = 0.01). We conclude that progesterone blunts whereas estradiol enhances carotid-vasomotor baroreflex sensitivity, perhaps explaining why no differences in sympathetic baroreflex sensitivity are commonly reported between low and high combined hormone phases of the menstrual cycle.

Short-term administration of progesterone and estradiol independently alter carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women

PubMed Central

Brunt, Vienna E.; Miner, Jennifer A.; Kaplan, Paul F.; Halliwill, John R.; Strycker, Lisa A.

2013-01-01

The individual effects of estrogen and progesterone on baroreflex function remain poorly understood. We sought to determine how estradiol (E2) and progesterone (P4) independently alter the carotid-cardiac and carotid-vasomotor baroreflexes in young women by using a hormone suppression and exogenous add-back design. Thirty-two young women were divided into two groups and studied under three conditions: 1) after 4 days of endogenous hormone suppression with a gonadotropin releasing hormone antagonist (control condition), 2) after continued suppression and 3 to 4 days of supplementation with either 200 mg/day oral progesterone (N = 16) or 0.1 to 0.2 mg/day transdermal 17β-estradiol (N = 16), and 3) after continued suppression and 3 to 4 days of supplementation with both hormones. Changes in heart rate (HR), mean arterial pressure (MAP), and femoral vascular conductance (FVC) were measured in response to 5 s of +50 mmHg external neck pressure to unload the carotid baroreceptors. Significant hormone effects on the change in HR, MAP, and FVC from baseline at the onset of neck pressure were determined using mixed model covariate analyses accounting for P4 and E2 plasma concentrations. Neither P4 (P = 0.95) nor E2 (P = 0.95) affected the HR response to neck pressure. Higher P4 concentrations were associated with an attenuated fall in FVC (P = 0.01), whereas higher E2 concentrations were associated with an augmented fall in FVC (P = 0.02). Higher E2 was also associated with an augmented rise in MAP (P = 0.01). We conclude that progesterone blunts whereas estradiol enhances carotid-vasomotor baroreflex sensitivity, perhaps explaining why no differences in sympathetic baroreflex sensitivity are commonly reported between low and high combined hormone phases of the menstrual cycle. PMID:23873800

Effect of posture on arterial baroreflex control of heart rate in humans

NASA Technical Reports Server (NTRS)

Harrison, M. H.; Rittenhouse, D.; Greenleaf, J. E.

1986-01-01

The effects of blood-volume redistribution induced by postural changes on baroreflex activity are investigated. The central blood volume and baroreceptor functions of ten males between 23-51 years old were examined while they were in the head-up tilt (HUT), head-down tilt (HDT), and supine positions. It is observed that during HDT at 15 deg the pulse interval over the first five cardiac cycles following neck suction onset is 51 + or - 18 ms longer, at 30 deg it is 61 + or - 20 ms longer, and at 45 deg it is 74 + or - 35 ms longer than at supine; during HUT at 15 deg the pulse interval is 25 + or - 9 ms shorter than when supine, but for the 30 and 45 deg there is no significant difference in pulse interval detected. The data reveal that posture does modify arterial baroreflex control of heart rate.

Signal transduction of aortic and carotid sinus baroreceptors is not modified by central command during spontaneous motor activity in decerebrate cats.

PubMed

Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

2014-05-15

Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors. Copyright © 2014 the American Physiological Society.

A computational analysis of the long-term regulation of arterial pressure

PubMed Central

Beard, Daniel A.

2013-01-01

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. representing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex. PMID:24555102

A computational analysis of the long-term regulation of arterial pressure.

PubMed

Beard, Daniel A; Pettersen, Klas H; Carlson, Brian E; Omholt, Stig W; Bugenhagen, Scott M

2013-01-01

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production-the acute pressure-diuresis and pressure-natriuresis curves-physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the "Guyton-Coleman model", no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. representing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex.

Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans.

PubMed

Mozer, Michael T; Holbein, Walter W; Joyner, Michael J; Curry, Timothy B; Limberg, Jacqueline K

2016-07-01

The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low-dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5-min normoxia (~99% SpO2), followed by 5-min hypoxia (~84% SpO2). Blood pressure (intra-arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P < 0.01). Using the spectrum analysis approach, the fall in scBRS with hypoxia was attenuated with infusion of low-dose dopamine (P < 0.01). The decrease in baroreflex sensitivity to rising pressures (scBRS "up-up") was also attenuated with low-dose dopamine (P < 0.05). However, dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS "down-down"; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low-dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt.

PubMed

Aslan, Sevda C; Randall, David C; Donohue, Kevin D; Knapp, Charles F; Patwardhan, Abhijit R; McDowell, Susan M; Taylor, Robert F; Evans, Joyce M

2007-03-01

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.

Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

PubMed

Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

2016-10-01

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade. Copyright © 2016 the American Physiological Society.

Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

PubMed Central

Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

2015-01-01

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

NASA Technical Reports Server (NTRS)

Moffitt, J. A.; Schadt, J. C.; Hasser, E. M.

1999-01-01

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

Reflex effects on renal nerve activity characteristics in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Sawin, L L

1997-11-01

The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.

Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension

PubMed Central

Iliescu, Radu; Tudorancea, Ionut; Irwin, Eric D.

2013-01-01

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation—current therapies in patients with resistant hypertension, who are commonly obese—restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1–4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure. PMID:23913707

Angiotensin II enhances norepinephrine spillover during sympathetic activation in conscious rabbits.

PubMed

Noshiro, T; Shimizu, K; Way, D; Miura, Y; McGrath, B P

1994-05-01

To investigate the potential modulating influence of angiotensin II (ANG II) on sympathetic activity in response to changes in baroreflex activity, renal and total norepinephrine (NE) spillover rates were examined during sodium nitroprusside (SNP) and phenylephrine (PE) infusions in four groups of conscious rabbits: 1) saline (control); 2) subpressor ANG II (ANG II, 2 ng.kg-1.min-1); 3) enalaprilat (MK-422, 200 micrograms/kg and 3.3 micrograms.kg-1.min-1); and 4) MK plus ANG II (MK+ANG II). Upper plateaus of baroreflex-NE spillover curves for renal and total NE spillover were reduced in the MK group (25 and 81 ng/min) compared with control (38 and 125 ng/min) and MK+ANG II (37 and 155 ng/min). To investigate the interaction of ANG II and sympathetic activity during treadmill exercise, hindlimb NE spillover rate was examined in three groups of rabbits: 1) control, 2) MK, and 3) MK+ANG II. Exercise at 6 and 12 m/min produced similar effort-related hemodynamic responses in the three groups. At maximal exercise, hindlimb NE spillover was reduced in the MK group (29 +/- 3 ng/min) compared with control (62 +/- 17 ng/min, P < 0.05) and MK+ANG II group (51 +/- 10 ng/min). It is concluded that endogenous ANG II enhances sympathetic activity during pharmacological (baroreflex) and physiological stimulation.

Cardiovascular function following reduced aerobic activity

NASA Technical Reports Server (NTRS)

Raven, P. B.; Welch-O'Connor, R. M.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure-volume relationship resulted in the reduced LBNP tolerance, despite the accentuated aortic and cardiopulmonary baroreflex function following deconditioning.

Baroreflex regulation of blood pressure during dynamic exercise

NASA Technical Reports Server (NTRS)

Raven, P. B.; Potts, J. T.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

From the work of Potts et al. Papelier et al. and Shi et al. it is readily apparent that the arterial (aortic and carotid) baroreflexes are reset to function at the prevailing ABP of exercise. The blood pressure of exercise is the result of the hemodynamic (cardiac output and TPR) responses, which appear to be regulated by two redundant neural control systems, "Central Command" and the "exercise pressor reflex". Central Command is a feed-forward neural control system that operates in parallel with the neural regulation of the locomotor system and appears to establish the hemodynamic response to exercise. Within the central nervous system it appears that the HLR may be the operational site for Central Command. Specific neural sites within the HLR have been demonstrated in animals to be active during exercise. With the advent of positron emission tomography (PET) and single-photon emission computed tomography (SPECT), the anatomical areas of the human brain related to Central Command are being mapped. It also appears that the Nucleus Tractus Solitarius and the ventrolateral medulla may serve as an integrating site as they receive neural information from the working muscles via the group III/IV muscle afferents as well as from higher brain centers. This anatomical site within the CNS is now the focus of many investigations in which arterial baroreflex function, Central Command and the "exercise pressor reflex" appear to demonstrate inhibitory or facilitatory interaction. The concept of whether Central Command is the prime mover in the resetting of the arterial baroreceptors to function at the exercising ABP or whether the resetting is an integration of the "exercise pressor reflex" information with that of Central Command is now under intense investigation. However, it would be justified to conclude, from the data of Bevegard and Shepherd, Dicarlo and Bishop, Potts et al., and Papelier et al. that the act of exercise results in the resetting of the arterial baroreflex. In addition, if, as we have proposed, the cardiopulmonary baroreceptors primarily monitors and reflexly regulates cardiac filling volume, it would seem from the data of Mack et al. and Potts et al. that the cardiopulmonary baroreceptor is also reset at the beginning of exercise. Therefore, investigations of the neural mechanisms of regulation involving Central Command and cardiopulmonary afferents, similar to those being undertaken for the arterial baroreflex, need to be established.

New indices from microneurography to investigate the arterial baroreflex.

PubMed

Laurin, Alexandre; Lloyd, Matthew G; Hachiya, Tesshin; Saito, Mitsuru; Claydon, Victoria E; Blaber, Andrew

2017-06-01

Baroreflex-mediated changes in heart rate and vascular resistance in response to variations in blood pressure are critical to maintain homeostasis. We aimed to develop time domain analysis methods to complement existing cross-spectral techniques in the investigation of the vascular resistance baroreflex response to orthostatic stress. A secondary goal was to apply these methods to distinguish between levels of orthostatic tolerance using baseline data. Eleven healthy, normotensive males participated in a graded lower body negative pressure protocol. Within individual neurogenic baroreflex cycles, the amount of muscle sympathetic nerve activity (MSNA), the diastolic pressure stimulus and response amplitudes, diastolic pressure to MSNA burst stimulus and response times, as well as the stimulus and response slopes between diastolic pressure and MSNA were computed. Coherence, gain, and frequency of highest coherence between systolic/diastolic arterial pressure (SAP/DAP) and RR-interval time series were also computed. The number of MSNA bursts per low-frequency cycle increased from 2.55 ± 0.68 at baseline to 5.44 ± 1.56 at -40 mmHg of LBNP Stimulus time decreased (3.21 ± 1.48-1.46 ± 0.43 sec), as did response time (3.47 ± 0.86-2.37 ± 0.27 sec). At baseline, DAP-RR coherence, DAP-RR gain, and the time delay between decreases in DAP and MSNA bursts were higher in participants who experienced symptoms of presyncope. Results clarified the role of different branches of the baroreflex loop, and suggested functional adaptation of neuronal pathways to orthostatic stress. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.

PubMed

Silva, Bruno M; Barbosa, Thales C; Neves, Fabricia J; Sales, Allan K; Rocha, Natalia G; Medeiros, Renata F; Pereira, Felipe S; Garcia, Vinicius P; Cardoso, Fabiane T; Nobrega, Antonio C L

2014-12-01

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses

NASA Technical Reports Server (NTRS)

Convertino, Victor A.; Ratliff, Duane A.; Doerr, Donald F.; Ludwig, David A.; Muniz, Gary W.; Benedetti, Erik; Chavarria, Jose; Koreen, Susan; Nguyen, Claude; Wang, Jeff

2003-01-01

INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

Aortic baroreflex control of heart rate after 15 days of simulated microgravity exposure

NASA Technical Reports Server (NTRS)

Crandall, Craig G.; Engelke, Keith A.; Convertino, Victor A.; Raven, Peter B.

1994-01-01

To determine the effects of simulated microgravity on aortic baroreflex control of heart rate, we exposed seven male subjects to 15 days of bed rest in the 6 deg head-down position. The sensitivity of the aortic-cardiac baroreflex was determined during a steady-state phenylephrine-induced increase in mean arterial pressure combined with lower body negative pressure to counteract central venous pressure increases and neck pressure to offset the increased carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in mean arterial pressure between baseline conditions and aortic baroreceptor-isolated conditions (i.e., phenylephrine + lower body negative pressure + neck pressure stage). Fifteen days of head-down tilt increased the gain of the aortic-cardiac baroreflex. Reductions in blood volume and/or maximal aerobic capacity may represent the underlying mechanism(s) responsible for increased aortic baroreflex responsiveness after exposure to a ground-based analogue of microgravity.

Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study.

PubMed

Seravalle, Gino; Piperno, Alberto; Mariani, Raffaella; Pelloni, Irene; Facchetti, Rita; Dell'Oro, Raffaella; Cuspidi, Cesare; Mancia, Giuseppe; Grassi, Guido

2016-03-21

Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown. In 18 males with primary HH (age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy. Haemochromatosis patients displayed elevated serum iron indices while other haemodynamic and metabolic variables were superimposable to ones seen in 12 healthy subjects (C). Muscle sympathetic nerve activity was significantly greater in HH than C (64.8 ± 13.3 vs. 37.8 ± 6.7 bs/100 hb, P < 0.01). Iron depletion caused a significant reduction in serum ferritin, transferrin saturation, and MSNA (from 64.8 ± 13.3 to 39.2 ± 9.2 bs/100 hb, P < 0.01) and a significant improvement in baroreflex-MSNA modulation. This was paralleled by a significant increase in the high-frequency HR variability and by a significant reduction in the low-frequency systolic BP variability components. Before after iron depletion therapy, MSNA was significantly and directly related to transferrin saturation, liver iron concentration, and iron removed, while the MSNA reductions observed after the procedure were significantly and inversely related to the baroreflex-MSNA increases detected after iron depletion. In C, all variables remained unchanged following 1 month observation. These data provide the first evidence that in HH iron overload is associated with an hyperadrenergic state and a baroreflex alteration, which are reversed by iron depletion. These findings underline the importance of iron overload in modulating sympathetic activation, possibly participating at the elevated cardiovascular risk reported in HH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Cardiovascular autonomic modulation and activity of carotid baroreceptors at altitude.

PubMed

Bernardi, L; Passino, C; Spadacini, G; Calciati, A; Robergs, R; Greene, R; Martignoni, E; Anand, I; Appenzeller, O

1998-11-01

1. To assess the effects of acute exposure to high altitude on baroreceptor function in man we evaluated the effects of baroreceptor activation on R-R interval and blood pressure control at high altitude. We measured the low-frequency (LF) and high-frequency (HF) components in R-R, non-invasive blood pressure and skin blood flow, and the effect of baroreceptor modulation by 0. 1-Hz sinusoidal neck suction. Ten healthy sea-level natives and three high-altitude native, long-term sea-level residents were evaluated at sea level, upon arrival at 4970 m and 1 week later.2. Compared with sea level, acute high altitude decreased R-R and increased blood pressure in all subjects [sea-level natives: R-R from 1002+/-45 to 775+/-57 ms, systolic blood pressure from 130+/-3 to 150+/-8 mmHg; high-altitude natives: R-R from 809+/-116 to 749+/-47 ms, systolic blood pressure from 110+/-12 to 125+/-11 mmHg (P<0.05 for all)]. One week later systolic blood pressure was similar to values at sea level in all subjects, whereas R-R remained elevated in sea-level natives. The low-frequency power in R-R and systolic blood pressure increased in sea-level natives [R-R-LF from 47+/-8 to 65+/-10% (P<0.05), systolic blood pressure-LF from 1.7+/-0. 3 to 2.6+/-0.4 ln-mmHg2 (P<0.05)], but not in high-altitude natives (R-R-LF from 32+/-13 to 38+/-19%, systolic blood pressure-LF from 1. 9+/-0.5 to 1.7+/-0.8 ln-mmHg2). The R-R-HF decreased in sea-level natives but not in high-altitude natives, and no changes occurred in systolic blood pressure-HF. These changes remained evident 1 week later. Skin blood flow variability and its spectral components decreased markedly at high altitude in sea-level natives but showed no changes in high-altitude natives. Neck suction significantly increased the R-R- and systolic blood pressure-LF in all subjects at both sea level and high altitude.3. High altitude induces sympathetic activation in sea-level natives which is partially counteracted by active baroreflex. Despite long-term acclimatization at sea level, high-altitude natives also maintain active baroreflex at high altitude but with lower sympathetic activation, indicating a persisting high-altitude adaptation which may be genetic or due to baroreflex activity not completely lost by at least 1 year's sea-level residence.

Impact of exercise training associated to pyridostigmine treatment on autonomic function and inflammatory profile after myocardial infarction in rats.

PubMed

Feriani, Daniele J; Souza, Gabriel I H; Carrozzi, Nicolle M; Mostarda, Cristiano; Dourado, Paulo M M; Consolim-Colombo, Fernanda M; De Angelis, Kátia; Moreno, Heitor; Irigoyen, Maria Cláudia; Rodrigues, Bruno

2017-01-15

The effects of exercise training (ET) associated with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on inflammatory profile after myocardial infarction (MI), are unclear. Male Wistar rats were randomly assigned to: control (C); sedentary+infarcted (I); sedentary+infarcted treated with PYR (IP); infarcted submitted to aerobic exercise training (IT); and infarcted submitted to treatment with PYR and aerobic exercise training (ITP). After 12weeks of ET (50-70% maximal running speed; 1h a day, 5days a week) and/or PYR treatment (0.14mg/mL on drink water), hemodynamic, autonomic and cytokines expression were performed. We observed that both aerobic ET, associated or not with PYR treatment in MI animals, were able to: reduced MI area, improved systolic and diastolic function, baroreflex sensitivity, cardiovascular autonomic modulation, and tonic activity of the sympathetic and parasympathetic nervous system. Also, they led to a reduction of inflammatory profile measured at plasma, left ventricle and soleus skeletal muscle. However, additional effects were observed when ET and PYR were associated, such as an increase in vagal tonus and modulation, reduction of MI area, interferon-γ and tumor necrosis factor-α (TNF-α), as well as an increase of interleukin-10/TNF-α ratio on left ventricle. These data suggest that associating ET and PYR promotes some additional benefits on cardiovascular autonomic modulation and inflammatory profile in infarcted rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Central endogenous histamine modulates sympathetic outflow through H3 receptors in the conscious rabbit

PubMed Central

Charles, Julian; Angus, James A; Wright, Christine E

2003-01-01

This study examined the role of histamine H3 receptors in vagal and sympathetic autonomic reflexes in the conscious rabbit, and in rabbit and guinea-pig isolated right atria. The baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch-like and nasopharyngeal reflexes were assessed after these treatments (i.v.; with H1 and H2 receptor block): (i) vehicle (saline; n=11); (ii) H3 receptor agonist, (R)-α-methylhistamine (R-α-MH) 100 μg kg−1+100 μg kg−1 h−1 (n=9); (iii) H3 receptor antagonist, thioperamide 1 mg kg−1+1 mg kg−1 h−1 (n=11); (iv) R-α-MH and thioperamide (n=6); and (v) H2 and H3 antagonist, burimamide 6.3 mg kg−1+6.3 mg kg−1 h−1 (n=4). R-α-MH caused a thioperamide-sensitive fall in mean arterial pressure (MAP) of 8±1 mmHg and tachycardia of 18±2 bpm (P<0.0005). Burimamide was without effect, however thioperamide elicited an increase in MAP of 4±1 mmHg (P<0.01), but no change in heart rate (HR). R-α-MH caused a 44% decrease in the average gain of the baroreflex (P=0.0001); this effect was antagonised by thioperamide. Thioperamide caused a parallel rightward shift in the barocurve with an increase in MAP of 5 mmHg (P<0.05). Burimamide had no effect on the baroreflex. The vagally mediated bradycardia elicited by the Bezold-Jarisch and nasopharyngeal reflexes was unaffected by H3 receptor ligand administration. R-α-MH (⩽10 μM) caused a thioperamide-sensitive depression of both sympathetic and vagal responses in guinea-pig atria, but had no effect in rabbit atria. As H3 receptor activation caused a significant decrease in baroreflex gain without affecting HR range, the former is unlikely to be simply due to peripheral sympatholysis (supported by the lack of effect in isolated atria). Central H3 receptors may have a tonic role in the baroreflex as thioperamide caused a rightward resetting of the barocurve. In contrast, the peripherally acting H3 antagonist burimamide was without effect. These findings suggest a role for central histamine H3 receptors in cardiovascular homeostasis in the rabbit. PMID:12839877

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

PubMed Central

dos Santos, Marcelo R.; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; de Souza, Francis R.; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population. PMID:29791601

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users.

PubMed

Santos, Marcelo R Dos; Sayegh, Ana L C; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R de; Toschi-Dias, Edgar; Bortolotto, Luiz A; Yonamine, Mauricio; Negrão, Carlos E; Alves, Maria-Janieire N N

2018-05-21

Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

A single inhalation exposure to acrolein desensitizes baroreflex responsiveness in Wistar-Kyoto and Spontaneously Hypertensive rats.

EPA Science Inventory

Arterial baroreflex is one of the body's homeostatic mechanisms that regulate blood pressure (BP) by changing heart rate (HR) and vasoconstriction. Increases in BP reflexively cause HR to decrease, whereas decreases in BP depress the baroreflex and cause HR to rise. As such, baro...

Baroreflex Responses to Acute Changes in Blood Volume in Humans

NASA Technical Reports Server (NTRS)

Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

1990-01-01

To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro-reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationship, of the cardio-pulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venous Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). The results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

STS-55 crewmembers work in the SL-D2 module onboard OV-102

NASA Image and Video Library

1993-05-06

STS055-22-004 (26 April-6 May 1993) --- Four of the seven crew members who spent 10 days aboard the Space Shuttle Columbia are pictured during a brief shift overlap period in the Spacelab D-2 Science Module. Left to right are Jerry L. Ross, Ulrich Walter, Bernard A. Harris, Jr. and Hans Schlegel. Ross, STS-55 payload commander, is changing a sample in a materials processing furnace; Walter, a German payload specialist is in the midst of a baroreflex test and fellow payload specialist Schlegel assists mission specialist and physician Harris with a physiological test at the "Anthrorack".

Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring.

PubMed

Zhang, Yu-Ping; Huo, Yan-Li; Fang, Zhi-Qin; Wang, Xue-Fang; Li, Jian-Dong; Wang, Hai-Ping; Peng, Wei; Johnson, Alan Kim; Xue, Baojian

2018-05-01

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

Carotid baroreflex response following 30 days exposure to simulated microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Doerr, D. F.; Eckberg, D. L.; Fritsch, J. M.; Vernikos-Danellis, J.

1989-01-01

The mechanism of the carotid-baroreflex response to weightlessness was investigated in human subjects exposed to simulated microgravity (30 days of 6-day head-down bed rest followed by 5 days of recovery). Baroreceptor-cardiac reflex responses were elicited by a complex sequence of pressure changes delivered to a neck chamber device. The shape of the sigmoid baroreceptor-cardiac response curve was examined for alterations and the occurrence of resetting, as well as for a possible association of the impaired baroreflex function with hypotension during the postexposure orthostatic stress. It was found that the exposure to head-down bed rest caused a significant shift on the R-R interval axis, which paralleled reductions and elevations in baseline HR such that the baseline R-R (operational point) remained in the same position on the response curve. This shift in the location of the reflex relation indicates a significant resetting of the carotid baroreceptors, which may represent an appropriate adaptation which contributes to the maintenance of a constant resting arterial blood pressure before, during, and after bed rest, observed in these study.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

PubMed

Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

Effects of whole-body vibration on heart rate variability: acute responses and training adaptations.

PubMed

Wong, Alexei; Figueroa, Arturo

2018-05-18

Heart rate variability (HRV) is a noninvasive and practical measure of cardiac autonomic nervous system function, mainly the sympathetic and parasympathetic modulations of heart rate. A low HRV has been shown to be indicative of compromised cardiovascular health. Interventions that enhance HRV are therefore beneficial to cardiovascular health. Whole-body vibration (WBV) training has been proposed as an alternative time-efficient exercise intervention for the improvement of cardiovascular health. In this review, we discuss the effect of WBV both acute and after training on HRV. WBV training appears to be a useful therapeutic intervention to improve cardiac autonomic function in different populations, mainly through decreases in sympathovagal balance. Although the mechanisms by which WBV training improves symphathovagal balance are not yet well understood; enhancement of baroreflex sensitivity, nitric oxide bioavailability and angiotensin II levels seem to play an important role. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training.

PubMed

Silva, Bruno M; Neves, Fabricia J; Negrão, Marcelo V; Alves, Cleber R; Dias, Rodrigo G; Alves, Guilherme B; Pereira, Alexandre C; Rondon, Maria U; Krieger, José E; Negrão, Carlos E; DA Nóbrega, Antonio Claudio Lucas

2011-09-01

There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training. Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (VO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day(-1), during 18 wk). Training increased VO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% ± 89% vs polymorphic (-786TC/CC) = -28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = -18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% ± 56% vs -41% ± 50%, median ± quartile range, P = 0.04). The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.

Sleep-mediated heart rate variability after bilateral carotid body tumor resection.

PubMed

Niemeijer, Nicolasine D; Corssmit, Eleonora P M; Reijntjes, Robert H A M; Lammers, Gert Jan; van Dijk, J Gert; Thijs, Roland D

2015-04-01

The carotid bodies are thought to play an important role in sleep-dependent autonomic changes. Patients who underwent resection of bilateral carotid body tumors have chronically attenuated baroreflex sensitivity. These subjects provide a unique opportunity to investigate the role of the baroreflex during sleep. One-night ambulatory polysomnography (PSG) recording. Participants' homes. Nine patients with bilateral carotid body tumor resection (bCBR) (four women, mean age 50.4 ± 7.2 years) and nine controls matched for age, gender, and body mass index. N/A. Sleep parameters were obtained from PSG. Heart rate (HR) and its variability were calculated using 30-s epochs. In bCBR patients, HR was slightly but not significantly increased during wake and all sleep stages. The effect of sleep on HR was similar for patients and controls. Low frequency (LF) power of the heart rate variability spectrum was significantly lower in bCBR patients in active wakefulness, sleep stage 1 and REM sleep. No differences were found between patients and controls for high frequency (HF) power and the LF/HF ratio. Bilateral carotid body tumor resection (bCBR) is associated with decreased low frequency power during sleep, suggesting impaired baroreflex function. Despite this, sleep-related heart rate changes were similar between bCBR patients and controls. These findings suggest that the effects of sleep on heart rate are predominantly generated through central, non-baroreflex mediated pathways. © 2015 Associated Professional Sleep Societies, LLC.

Estimation of arterial baroreflex sensitivity in relation to carotid artery stiffness.

PubMed

Lipponen, Jukka A; Tarvainen, Mika P; Laitinen, Tomi; Karjalainen, Pasi A; Vanninen, Joonas; Koponen, Timo; Lyyra-Laitinen, Tiina

2012-01-01

Arterial baroreflex has a significant role in regulating blood pressure. It is known that increased stiffness of the carotid sinus affects mecanotransduction of baroreceptors and therefore limits baroreceptors capability to detect changes in blood pressure. By using high resolution ultrasound video signal and continuous measurement of electrocardiogram (ECG) and blood pressure, it is possible to define elastic properties of artery simultaneously with baroreflex sensitivity parameters. In this paper dataset which consist 38 subjects, 11 diabetics and 27 healthy controls was analyzed. Use of diabetic and healthy test subjects gives wide scale of arteries with different elasticity properties, which provide opportunity to validate baroreflex and artery stiffness estimation methods.

Central N-acetylcysteine effects on baroreflex in juvenile spontaneously hypertensive rats.

PubMed

Valenti, Vitor E; De Abreu, Luiz Carlos; Sato, Monica A; Saldiva, Paulo H N; Fonseca, Fernando L A; Giannocco, Gisele; Riera, Andreas R P; Ferreira, Celso

2011-06-01

In this study, we evaluated the acute effects of central NAC administration on baroreflex in juvenile SHR and Wistar Kyoto (WKY) rats. Male SHR and WKY rats (8-10 weeks old) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. After basal MAP and HR recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus). Baroreflex was evaluated before, 5, 15, 30 and 60 minutes after NAC injection into the 4th V. Vehicle treatment did not change baroreflex responses in WKY and SHR. Central NAC slightly but significantly increased basal HR at 15 minutes and significantly reduced PHE-induced increase in MAP 30 and 60 minutes after NAC injection (p < 0.05) in WKY rats. In relation to SHR, NAC decreased HR range 15 and 30 minutes after its administration. In conclusion, acute NAC into the 4th V does not improve baroreflex in juvenile SHR.

Baroreflex Responses to Acute Changes in Blood Volume in Humans

NASA Technical Reports Server (NTRS)

Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

1990-01-01

To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro- reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venotis Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 q 1.71, -4.36 q 1.38, and -2.56 q 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulnionary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

NASA Technical Reports Server (NTRS)

Iwasaki, K. I.; Zhang, R.; Zuckerman, J. H.; Pawelczyk, J. A.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

2000-01-01

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Neuroactive Steroids: Receptor Interactions and Responses

PubMed Central

Tuem, Kald Beshir; Atey, Tesfay Mehari

2017-01-01

Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors. Among these, NSs (especially allopregnanolone) have high potency and extensive GABA-A receptors and hence demonstrate anticonvulsant, anesthetic, central cytoprotectant, and baroreflex inhibitory effects. NSs are also involved in mood and learning via serotonin and anti-nociceptive activity via T-type voltage-gated Ca2+ channels. Moreover, they are modulators of mitochondrial function, synaptic plasticity, or regulators of apoptosis, which have a role in neuroprotective via voltage-dependent anion channels receptors. For proper functioning, NASs need to be in their normal level, whereas excess and deficiency may lead to abnormalities. When they are below the normal, NSs could have a part in development of depression, neuro-inflammation, multiple sclerosis, experimental autoimmune encephalitis, epilepsy, and schizophrenia. On the other hand, stress and attention deficit disorder could occur during excessive level. Overall, NASs are very important molecules with major neuropsychiatric activity. PMID:28894435

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Ludwig, D. A.; Reister, C.; Fanton, J. W.; Ewert, D.; Convertino, V. A.

2001-01-01

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Respiratory modulation of human autonomic function: long‐term neuroplasticity in space

PubMed Central

Diedrich, André; Cooke, William H.; Biaggioni, Italo; Buckey, Jay C.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Kuusela, Tom A.; Tahvanainen, Kari U.O.; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J.; Levine, Benjamin D.; Adams‐Huet, Beverley; Robertson, David; Blomqvist, C. Gunnar

2016-01-01

Key points We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance.Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity.Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth.Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth.Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts’ abilities to modulate both burst areas and frequencies during apnoea were sharply diminished.Spaceflight triggers long‐term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes. Abstract We studied six healthy astronauts five times, on Earth, in space on the first and 12th or 13th day of the 16 day Neurolab Space Shuttle mission, on landing day, and 5–6 days later. Astronauts followed a fixed protocol comprising controlled and random frequency breathing and apnoea, conceived to perturb their autonomic function and identify changes, if any, provoked by microgravity exposure. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations and volumes, and peroneal nerve muscle sympathetic activity on Earth (in the supine position) and in space. (Sympathetic nerve recordings were made during three sessions: preflight, late mission and landing day.) Arterial pressure changed systematically from preflight levels: pressure fell during early microgravity exposure, rose as microgravity exposure continued, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations (root mean square of successive normal R‐R intervals; and proportion of successive normal R‐R intervals greater than 50 ms, divided by the total number of normal R‐R intervals) rose significantly during early microgravity exposure, fell as microgravity exposure continued, and descended to preflight levels upon return to Earth. Sympathetic mechanisms also changed. Burst frequencies (but not areas) during fixed frequency breathing were greater than preflight in space and on landing day, but their control during apnoea was sharply altered: astronauts increased their burst frequencies from already high levels, but they could not modulate either burst areas or frequencies appropriately. Space travel provokes long‐lasting sympathetic and vagal neuroplastic changes in healthy humans. PMID:27029027

Association of impaired baroreflex sensitivity and increased arterial stiffness in peritoneal dialysis patients.

PubMed

Gupta, Amit; Jain, Gaurav; Kaur, Manpreet; Jaryal, Ashok Kumar; Deepak, Kishore Kumar; Bhowmik, Dipankar; Agarwal, Sanjay Kumar

2016-04-01

Peritoneal dialysis patients have high cardiovascular morbidity and mortality. The underlying mechanism of cardiovascular dysfunction remains unclear. Large arterial stiffness in chronic kidney disease (CKD) patients leads to increase in pulse wave velocity (PWV) and decrease in baroreflex sensitivity (BRS). Impairment in baroreflex function could be attributed to the alteration in mechanical properties of large vessels due to arterial remodeling observed in these patients. The present study was designed to study the association of BRS and PWV in peritoneal dialysis (PD) patients. 42 CKD patients (21--without dialysis and 21--on PD) and 25 healthy controls were recruited in this study. BRS was determined by spontaneous sequence method. Short-term heart rate variability (HRV) and blood pressure variability (BPV) were assessed using power spectrum analysis of RR intervals and systolic blood pressure by time domain and frequency domain analysis. Arterial stiffness indices were assessed by carotid-femoral PWV using Sphygmocor Vx device (AtCor Medical, Australia). CKD patients had significantly high PWV and low BRS as compared to healthy controls. PWV had a significant negative correlation with BRS in CKD patients (Spearman r = -0.7049, P < 0.0001; BRS-Systolic BP). On subgroup analysis, PWV was higher with lower BRS in CKD patients on peritoneal dialysis (CKD-PD) as compared to those not on dialysis (CKD-ND). Negative relationship between PWV and BRS was found in both the groups. In addition, BRS was found to have a positive correlation with HRV in CKD patients as well as both the subgroups. Reduction in BRS is strongly associated with increase in PWV in PD patients. Large arterial stiffness probably explains this simultaneous impairment in baroreflex functioning and increase in pulse wave velocity observed in these patients. CKD patients are characterized by poor hemodynamic profile (low BRS, high PWV, and low HRV), and peritoneal dialysis patients had further worsened profile as compared to non-dialysis group.

Role of central command in carotid baroreflex resetting in humans during static exercise

NASA Technical Reports Server (NTRS)

Ogoh, S.; Wasmund, W. L.; Keller, D. M.; O-Yurvati, A.; Gallagher, K. M.; Mitchell, J. H.; Raven, P. B.

2002-01-01

The purpose of the experiments was to examine the role of central command in the exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30 % maximal voluntary contraction (MVC) static knee extension and flexion with manipulation of central command (CC) by patellar tendon vibration (PTV). The same subjects also performed static knee extension and flexion exercise without PTV at a force development that elicited the same ratings of perceived exertion (RPE) as those observed during exercise with PTV in order to assess involvement of the exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid changes in neck pressure and suction during steady state static exercise. Knee extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR-MAP to a lower operating pressure (P < 0.05) and knee flexion exercise with PTV (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating pressure (P < 0.05). Comparison between knee extension and flexion exercise at the same RPE with and without PTV found no difference in the resetting of the CBR-HR function curves (P > 0.05) suggesting the response was determined primarily by CC activation. However, the CBR-MAP function curves were reset to operating pressures determined by both exercise pressor reflex (EPR) and central command activation. Thus the physiological response to exercise requires CC activation to reset the carotid-cardiac reflex but requires either CC or EPR to reset the carotid-vasomotor reflex.

Additive effects of heating and exercise on baroreflex control of heart rate in healthy males.

PubMed

Peçanha, Tiago; Forjaz, Cláudia L M; Low, David A

2017-12-01

This study assessed the additive effects of passive heating and exercise on cardiac baroreflex sensitivity (cBRS) and heart rate variability (HRV). Twelve healthy young men (25 ± 1 yr, 23.8 ± 0.5 kg/m 2 ) randomly underwent two experimental sessions: heat stress (HS; whole body heat stress using a tube-lined suit to increase core temperature by ~1°C) and normothermia (NT). Each session was composed of a preintervention rest (REST1); HS or NT interventions; postintervention rest (REST2); and 14 min of cycling exercise [7 min at 40%HR reserve (EX1) and 7 min at 60%HR reserve (EX2)]. Heart rate and finger blood pressure were continuously recorded. cBRS was assessed using the sequence (cBRS SEQ ) and transfer function (cBRS TF ) methods. HRV was assessed using the indexes standard deviation of RR intervals (SDNN) and root mean square of successive RR intervals (RMSSD). cBRS and HRV were not different between sessions during EX1 and EX2 (i.e., matched heart rate conditions: EX1 = 116 ± 3 vs. 114 ± 3 and EX2 = 143 ± 4 vs. 142 ± 3 beats/min but different workloads: EX1 = 50 ± 9 vs. 114 ± 8 and EX2 = 106 ± 10 vs. 165 ± 8 W; for HS and NT, respectively; P < 0.01). However, when comparing EX1 of NT with EX2 of HS (i.e., matched workload conditions but with different heart rates), cBRS and HRV were significantly reduced in HS (cBRS SEQ  = 1.6 ± 0.3 vs. 0.6 ± 0.1 ms/mmHg, P < 0.01; SDNN = 2.3 ± 0.1 vs. 1.3 ± 0.2 ms, P < 0.01). In conclusion, in conditions matched by HR, the addition of heat stress to exercise does not affect cBRS and HRV. Alternatively, in workload-matched conditions, the addition of heat to exercise results in reduced cBRS and HRV compared with exercise in normothermia. NEW & NOTEWORTHY The present study assessed cardiac baroreflex sensitivity during the combination of heat and exercise stresses. This is the first study to show that prior whole body passive heating reduces cardiac baroreflex sensitivity and autonomic modulation of heart rate during exercise. These findings contribute to the better understanding of the role of thermoregulation on cardiovascular regulation during exercise.

Cardiovascular, cerebrovascular, and respiratory changes induced by different types of music in musicians and non-musicians: the importance of silence.

PubMed

Bernardi, L; Porta, C; Sleight, P

2006-04-01

To assess the potential clinical use, particularly in modulating stress, of changes in the cardiovascular and respiratory systems induced by music, specifically tempo, rhythm, melodic structure, pause, individual preference, habituation, order effect of presentation, and previous musical training. Measurement of cardiovascular and respiratory variables while patients listened to music. University research laboratory for the study of cardiorespiratory autonomic function. 12 practising musicians and 12 age matched controls. After a five minute baseline, presentation in random order of six different music styles (first for a two minute, then for a four minute track), with a randomly inserted two minute pause, in either sequence. Breathing rate, ventilation, carbon dioxide, RR interval, blood pressure, mid-cerebral artery flow velocity, and baroreflex. Ventilation, blood pressure, and heart rate increased and mid-cerebral artery flow velocity and baroreflex decreased with faster tempi and simpler rhythmic structures compared with baseline. No habituation effect was seen. The pause reduced heart rate, blood pressure, and minute ventilation, even below baseline. An order effect independent of style was evident for mid-cerebral artery flow velocity, indicating a progressive reduction with exposure to music, independent of style. Musicians had greater respiratory sensitivity to the music tempo than did non-musicians. Music induces an arousal effect, predominantly related to the tempo. Slow or meditative music can induce a relaxing effect; relaxation is particularly evident during a pause. Music, especially in trained subjects, may first concentrate attention during faster rhythms, then induce relaxation during pauses or slower rhythms.

Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

PubMed

Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

2014-07-01

Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

PubMed

Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

2016-11-01

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl 2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl 2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl 2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl 2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans

NASA Technical Reports Server (NTRS)

Kaufmann, H.; Biaggioni, I.; Voustianiouk, A.; Diedrich, A.; Costa, F.; Clarke, R.; Gizzi, M.; Raphan, T.; Cohen, B.

2002-01-01

It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.

Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans.

PubMed

Kaufmann, H; Biaggioni, I; Voustianiouk, A; Diedrich, A; Costa, F; Clarke, R; Gizzi, M; Raphan, T; Cohen, B

2002-04-01

It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.

Baroreflex-Mediated Heart Rate and Vascular Resistance Responses 24 h after Maximal Exercise

DTIC Science & Technology

2003-01-01

of normal physiological function in bedridden patients and astronauts. The implication for failure of CVP and plasma volume to return to baseline... FUNCTION , BLOOD PRES- SURE, CENTRAL VENOUS PRESSURE, PHENYLEPHRINE, NECK PRESSURE, LOWER BODY NEGATIVE PRESSURE, COUNTERMEASURES Increased incidence of...orthostatic hypotension and intol-erance in humans is associated with vascular hypovole-mia and attenuated cardiovascular reflex functions

Dialysate temperature adjustment as an effective treatment for baroreflex failure syndrome in hemodialysis patient.

PubMed

Tanabe, Natsumi; Takane, Koki; Yokoyama, Keitaro; Tanno, Yudo; Yamamoto, Izumi; Ohkido, Ichiro; Yokoo, Takashi

2014-09-17

Baroreflex failure syndrome is a rare disorder which causes labile blood pressure, headache, flushing, diaphoresis and emotional lability. It is caused by history of trauma or radiotherapy in the cervical legion, bilateral carotid-body tumor or resection of glossopharyngeal nerve. We experienced a case of hemodialysis patient who had difficulty in controlling blood pressure during dialysis because of his baroreflex failure syndrome and successfully controlled his blood pressure by adjusting dialysate temperature. We report a case of a 68-year-old CKD5 patient who had difficulty in hemodialysis treatment because of severe fluctuations in blood pressure with hypertensive attacks and hypotensive episodes which caused him a severe discomfort. His dialysis treatment was started in 2010 and since that time baroreflex failure syndrome has been suspected because of his clinical manifestations and history of radiotherapy in the cervical region for his lingual cancer in 1994. Baroreflex failure syndrome is diagnosed by symptoms and cold stressor test. We performed a cold stressor test on an experimental baroreflex failure syndrome mouse and induced a significant elevation of blood pressure. From this experimental finding of model mouse, we changed the patients dialysate temperature between 34-38° according to his change in blood pressure though 80-240 mmHg. From this attempt, his blood pressure was successfully controlled between 100-180 mmHg and he was able to continue hemodialysis without any discomfort. In our case, environmental stimulation such as temperature change modified the patients fluctuating blood pressure. Change of dialysate temperature could be an option for controlling the unstable blood pressure due to baroreflex failure syndrome.

Effects of noradrenaline on human vagal baroreflexes

NASA Technical Reports Server (NTRS)

Airaksinen, K. E.; Huikuri, H. V.; Huhti, L.; Kuusela, T. A.; Tahvanainen, K. U.; Tulppo, M.; Makikallio, T.; Eckberg, D. L.

2001-01-01

BACKGROUND: Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function. AIM: To understand better the role of NA in cardiovascular homeostasis. METHODS: We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz. RESULTS: The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (+/- SD) baseline level of 17.3+/-6.6 to 34.1+/-20.8 ms/mmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0+/-12.9 to 10.1+/-7.4 during the low NA infusion rate and to 6.2+/-6.2% during the high rate (P < 0.05 and 0.01, respectively). CONCLUSIONS: Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.

Carotid-cardiac baroreflex response and LBNP tolerance following resistance training

NASA Technical Reports Server (NTRS)

Tatro, D. L.; Dudley, G. A.; Convertino, V. A.

1992-01-01

The purpose of this study was to examine the effect of lower body resistance training on cardiovascular control mechanisms and blood pressure maintenance during an orthostatic challenge. Lower body negative pressure (LBNP) tolerance, carotid-cardiac baroreflex function (using neck chamber pressure), and calf compliance were measured in eight healthy males before and after 19 wk of knee extension and leg press training. Resistance training sessions consisted of four or five sets of 6-12 repetitions of each exercise, performed two times per week. Training increased strength 25 +/- 3 (SE) percent (P = 0.0003) and 31 +/- 6 percent (P = 0.0004), respectively, for the leg press and knee extension exercises. Average fiber size in biopsy samples of m. vastus lateralis increased 21 +/- 5 percent (P = 0.0014). Resistance training had no significant effect on LBNP tolerance. However, calf compliance decreased in five of the seven subjects measured, with the group average changing from 4.4 +/- 0.6 ml.mm Hg-1 to 3.9 +/- 0.3 ml.mm Hg-1 (P = 0.3826). The stimulus-response relationship of the carotid-cardiac baroreflex response shifted to the left on the carotid pressure axis as indicated by a reduction of 6 mm Hg in baseline systolic blood pressure (P = 0.0471). In addition, maximum slope increased from 5.4 +/- 1.3 ms.mm Hg-1 before training to 6.6 +/- 1.6 ms.mm Hg-1 after training (P = 0.0141). Our results suggest the possibility that high resistance, lower extremity exercise training can cause a chronic increase in sensitivity and resetting of the carotid-cardiac baroreflex.

Asymmetries in reciprocal baroreflex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome.

PubMed

Davydov, D M; Naliboff, B; Shahabi, L; Shapiro, D

2018-02-01

Objective measures of pain severity remain ill defined, although its accurate measurement is critical. Reciprocal baroreflex mechanisms of blood pressure (BP) control were found to impact differently on pain regulation, and thus their asymmetry was hypothesized to also connect to chronic pain duration and severity. Seventy-eight female patients with irritable bowel syndrome (IBS) and 27 healthy women were assessed for IBS severity and chronicity, negative affect, and various measures of resting autonomic function including BP, heart rate and its variability (HRV), baroreceptor-sensitivity to activations and inhibitions, gains of brady- and tachy-cardiac baro-responses, gains of BP falls/rises, and BP start points for these spontaneous baroreflexes. IBS directly and indirectly (through increased negative affect) was associated with asymmetry between baroreceptor activations/inhibitions compared to symmetrical baroreflex reciprocity in the healthy women. In the IBS group, independently of specific IBS symptoms, pain chronicity was associated with (i) decreased BP falls coupled with either (a) decreased tachycardia associated with lower disease severity (earlier "pain resilience" mechanism), or (b) decreased bradycardia associated with higher disease severity (later "pain decompensation" mechanism), or (ii) increased BP start point for baroreceptor activations coupled with either (a) BP increase (delayed "pain adaptation" mechanism) or (b) affect-related HRV decrease (delayed "pain aggravation" mechanism). We anticipate the findings to be a starting point for validating these autonomic metrics of pain suffering and pain coping mechanisms in other chronic pain syndromes to suggest them as biomarkers of its severity and duration for profiling and correct management of chronic pain patients. © 2017 John Wiley & Sons Ltd.

The influence of tobacco smoking on the relationship between pressure and flow in the middle cerebral artery in humans.

PubMed

Peebles, Karen C; Horsman, Helen; Tzeng, Yu-Chieh

2013-01-01

Cigarette smoking is associated with an increased risk of stroke but the mechanism is unclear. The study examined whether acute and chronic cigarette smoking alters the dynamic relationship between blood pressure and cerebral blood flow. We hypothesised that acute and chronic smoking would result in a cerebral circulation that was less capable of buffering against dynamic fluctuations in blood pressure. Further, these changes would be accompanied by a reduction in baroreflex sensitivity, which is reduced after smoking (acute smoking). We recruited 17 non-smokers and 15 habitual smokers (13 ± 5 pack years). Continuous measurements of mean cerebral blood flow velocity (transcranial Doppler ultrasound), blood pressure (finger photoplethysmography) and heart rate enabled transfer function analysis of the dynamic relationship between pressure and flow (gain, normalised gain, phase and coherence) and baroreflex sensitivity during supine rest before and after smoking a single cigarette (acute smoking). There were no between-group differences in gain, phase or coherence before acute smoking. However, both groups showed a reduction in gain and coherence, associated with a reduction in baroreflex sensitivity, and increase in phase after acute smoking. Contrary to our hypothesis, these findings suggest that in the face of a reduction in baroreflex sensitivity acute smoking may potentially improve the ability of the cerebral circulation to buffer against changes in blood pressure. However, chronic smoking did not alter the dynamic relationship between blood pressure and cerebral blood flow velocity. These results have implications on understanding mechanisms for attenuating stroke risk.

Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Ogoh, S.; Watenpaugh, D. E.; Wasmund, W.; Olivencia-Yurvati, A.; Smith, M. L.; Raven, P. B.

2001-01-01

We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.

The Baroreflex as a Long-Term Controller of Arterial Pressure

PubMed Central

Iliescu, Radu

2015-01-01

Because of resetting, a role for baroreflexes in long-term control of arterial pressure has been commonly dismissed in the past. However, in recent years, this perspective has changed. Novel approaches for determining chronic neurohormonal and cardiovascular responses to natural variations in baroreceptor activity and to electrical stimulation of the carotid baroreflex indicate incomplete resetting and sustained responses that lead to long-term alterations in sympathetic activity and arterial pressure. PMID:25729060

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in influencing the neural control of renal function.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Regulation of Renin Secretion and Arterial Pressure During Prolonged Baroreflex Activation: Influence of Salt Intake

PubMed Central

Hildebrandt, Drew A.; Irwin, Eric D.; Cates, Adam W.; Lohmeier, Thomas E.

2014-01-01

Chronic electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated as antihypertensive therapy for patients with resistant hypertension. However, the influence of variations in salt intake on blood pressure lowering during baroreflex activation has not been determined. As sensitivity of arterial pressure to salt intake is linked to the responsiveness of renin secretion, we determined steady-state levels of arterial pressure and neurohormonal responses in 6 dogs on low, normal, and high salt intakes ( 5, 40, 450 mmol/day, respectively) under control conditions and during a 7-day constant level of baroreflex activation. Under control conditions, there was no difference in mean arterial pressure at low (92±1) and normal (92±2 mmHg) sodium intakes, but pressure increased 9 ±2 mmHg during high salt. Plasma renin activity (2.01±0.23, 0.93±0.20, 0.01±0.01 ng ANGI/mL/hr) and plasma aldosterone (10.3±1.9, 3.5±0.5, 1.7±0.1ng/dL) were inversely related to salt intake, whereas there were no changes in plasma norepinephrine. Although mean arterial pressure (19-22 mmHg) and norepinephrine (20-40%) were lower at all salt intakes during baroreflex activation, neither the changes in pressure nor the absolute values for plasma renin activity or aldosterone in response to salt were different from control conditions. These findings demonstrate that suppression of sympathetic activity by baroreflex activation lowers arterial pressure without increasing renin release and indicate that changes in sympathetic activity are not primary mediators of the effect of salt on renin secretion. Consequently, blood pressure lowering during baroreflex activation is independent of salt intake. PMID:24935941

Physiology and pathophysiology of heart rate and blood pressure variability in humans: is power spectral analysis largely an index of baroreflex gain?

PubMed

Sleight, P; La Rovere, M T; Mortara, A; Pinna, G; Maestri, R; Leuzzi, S; Bianchini, B; Tavazzi, L; Bernardi, L

1995-01-01

1. It is often assumed that the power in the low- (around 0.10 Hz) and high-frequency (around 0.25 Hz) bands obtained by power spectral analysis of cardiovascular variables reflects sympathetic and vagal tone [corrected] respectively. An alternative model attributes the low-frequency band to a resonance in the control system that is produced by the inefficiently slow time constant of the reflex response to beat-to-beat changes in blood pressure effected by the sympathetic (with or without the parasympathetic) arm(s) of the baroreflex (De Boer model). 2. We have applied the De Boer model of circulatory variability to patients with varying baroreflex sensitivity to patients with varying baroreflex sensitivity and one normal subject, and have shown that the main differences in spectral power (for both low and high frequency) between and within subjects are caused by changes in the arterial baroreflex gain, particularly for vagal control of heart rate (R-R interval) and left ventricular stroke output. We have computed the power spectrum at rest and during neck suction (to stimulate carotid baroreceptors). We stimulated the baroreceptors at two frequencies (0.1 and 0.2 Hz), which were both distinct from the controlled respiration rate (0.25 Hz), in both normal subjects and heart failure patients with either sensitive or poor baroreflex control. 3. The data broadly confirm the De Boer model. The low-frequency (0.1 Hz) peak in either R-R or blood pressure variability) was spontaneously generated only if the baroreflex control of the autonomic outflow was relatively intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmented baroreflex heart rate gain after moderate-intensity, dynamic exercise

NASA Technical Reports Server (NTRS)

Halliwill, J. R.; Taylor, J. A.; Hartwig, T. D.; Eckberg, D. L.

1996-01-01

The occurrence of a sustained vasodilation and hypotension after acute, dynamic exercise suggests that exercise may alter arterial baroreflex mechanisms. Therefore, we assessed systemic hemodynamics, baroreflex regulation of heart rate, and cardiac vagal tone after 60 min of cycling at 60% peak oxygen consumption in 12 healthy, untrained men and women (ages 21-28 yr). We derived sigmoidal carotid-cardiac baroreflex relations by measurement of R-R interval changes induced by ramped, stepwise, R-wave-triggered changes in external neck pressure from 40 to -65 mmHg. We estimated tonic cardiac vagal control with power spectral analysis of R-R interval variability in the respiratory frequency band (0.2-0.3 Hz) during frequency- and tidal volume-controlled breathing. Both mean arterial pressure and total peripheral resistance were reduced postexercise [pressure: from 86 +/- 2 (mean +/- SE) to 81 +/- 2 mmHg; resistance: from 23 +/- 2 to 16 +/- 1 units; both P < 0.05]. Cardiac output was increased postexercise (from 3.9 +/- 0.3 to 5.5 +/- 0.5 l/min, P < 0.05). Both slope and range of the carotid-cardiac baroreflex relation were increased postexercise (slope: from 4.7 +/- 0.7 to 6.1 +/- 0.9 ms/mmHg; range: from 186 +/- 23 to 238 +/- 30 ms, P < 0.05). Respiratory R-R interval variability (cardiac vagal tone) was not changed at any time after exercise, whereas heart rate and plasma norepinephrine levels were elevated. Thus moderate-intensity, dynamic exercise increases heart rate and cardiac output, reduces peripheral vascular resistance, and augments baroreflex responsiveness. Our data suggest that augmented baroreflex heart rate gain restrains rather than contributes to postexercise hypotension, which appears to be mediated predominately by vasodilation.

[Vasovagal syncope and increased baroreceptor activity: evidence for increased sensibility of the baroreflex and its rapid reversal with acute administration of metoprolol].

PubMed

Pucciarelli, G; De Vecchis, R; Ebraio, F; Corigliano, G G

1997-07-01

In 17 patients suffering from recurrent episodes of vasovagal syncope as well as in 21 healthy subjects without clinical episodes of presyncope or syncope, we evaluated the reflex decrease in heart rate evoked by the phenilephrine test. In the syncopal patients, the measurements were taken 4-12 hours after the clinical appearance of syncope. We divided the syncopal patients as follows: 9 patients, undergoing pharmacological treatment, and 8 untreated patients (drug free arm). In the pharmacological arm of the study, an alternate, randomized administration of metoprolol (150 mg twice daily for 2 days) and verapamil (80 mg every 6 hours for 2 days) was provided. Therefore, in the pharmacological arm as well as in drug free patients, we tested again the baroreflex sensitivity, by means of iv phenilephrine bolus, 3 and 7 days after the clinical appearance of the syncopal event. The baroreflex sensitivity values were significantly higher in the syncopal group compared to the control group (21 +/- 5 vs 13 +/- 4.5 ms/mm Hg; p < 0.01). Of the two tested drugs, only the metoprolol produced a fast (day 3) decrease in baroreflex sensitivity. On the basis of measurements taken after 7 days, we noted a pattern of widespread reduction in baroreflex sensitivity values, found in both treated and untreated patients. In conclusion, patients with vasovagal syncope exhibited a more pronounced maximal parasympathetic activation compared to the control group. The high baroreflex sensitivity values were soon (day 3) reduced by metoprolol, but not by verapamil therapy; a spontaneous normalization in baroreflex sensitivity values was found 7 days after the clinical episode, regardless of therapy.

Variability in cardiovascular control: the baroreflex reconsidered.

PubMed

Karemaker, John M; Wesseling, Karel H

2008-03-01

Although blood pressure control is often viewed as a paradigmatic example of a "homeostatic" biological control system, blood pressure levels can fluctuate considerably over shorter and longer time scales. In modern signal analysis, coherence between heart rate and blood pressure variability is used to estimate baroreflex gain. However, the shorter the measurement period, the more variability this gain factor reveals. We review evidence that this variability is not due to the technique used for the estimation, but may be an intrinsic property of the circulatory control mechanisms. The baroreflex is reviewed from its evolutionary origin, starting in fishes as a reflex mechanism to protect the gills from excessively high pressures by slowing the heart via the (parasympathetic) vagus nerve. Baroreflex inhibition of cardiovascular sympathetic nervous outflow is a later development; the maximally possible extent of sympathetic activity probably being set in the central nervous system by mechanisms other than blood pressure per se. In the sympathetic outflow tract not only baroreflex inhibition but also as yet unidentified, stochastic mechanisms decide to pass or not pass on the sympathetic activity to the periphery. In this short essay, the "noisiness" of the baroreflex as nervous control system is stressed. This property is observed in all elements of the reflex, even at the--supposedly--most basic relation between afferent receptor nerve input and efferent--vagus--nerve output signal.

Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise.

PubMed

Hureau, Thomas J; Weavil, Joshua C; Thurston, Taylor S; Broxterman, Ryan M; Nelson, Ashley D; Bledsoe, Amber D; Jessop, Jacob E; Richardson, Russell S; Wray, D Walter; Amann, Markus

2018-04-15

We investigated the contribution of group III/IV muscle afferents to carotid baroreflex resetting during electrically evoked (no central command) and voluntary (requiring central command) isometric knee extension exercise. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive group III/IV leg muscle afferent feedback. Spontaneous carotid baroreflex control was assessed by loading and unloading the carotid baroreceptors with a variable pressure neck chamber. Group III/IV muscle afferents did not influence spontaneous carotid baroreflex responsiveness at rest or during exercise. Afferent feedback accounted for at least 50% of the exercise-induced increase in the carotid baroreflex blood pressure and heart rate operating points, adjustments that are critical for an appropriate cardiovascular response to exercise. These findings suggest that group III/IV muscle afferent feedback is, independent of central command, critical for the resetting of the carotid baroreflex blood pressure and heart rate operating points, but not for spontaneous baroreflex responsiveness. This study sought to comprehensively investigate the role of metabolically and mechanically sensitive group III/IV muscle afferents in carotid baroreflex responsiveness and resetting during both electrically evoked (EVO, no central command) and voluntary (VOL, requiring central command) isometric single-leg knee-extension (15% of maximal voluntary contraction; MVC) exercise. Participants (n = 8) were studied under control conditions (CTRL) and following lumbar intrathecal fentanyl injection (FENT) to inhibit μ-opioid receptor-sensitive lower limb muscle afferents. Spontaneous carotid baroreflex control of mean arterial pressure (MAP) and heart rate (HR) were assessed following rapid 5 s pulses of neck pressure (NP, +40 mmHg) or suction (NS, -60 mmHg). Resting MAP (87 ± 10 mmHg) and HR (70 ± 8 bpm) were similar between CTRL and FENT conditions (P > 0.4). In terms of spontaneous carotid baroreflex responsiveness, FENT did not alter the change in MAP or HR responses to NP (+13 ± 5 mmHg, P = 0.85; +9 ± 3 bpm; P = 0.99) or NS (-13 ± 5 mmHg, P = 0.99; -24 ± 11 bpm; P = 0.49) at rest or during either exercise protocol, which were of a remarkably similar magnitude to rest. In contrast, FENT administration reduced the exercise-induced resetting of the operating point for MAP and HR during both EVO (116 ± 10 mmHg to 100 ± 15 mmHg and 93 ± 14 bpm to 82 ± 10 bpm) and VOL (107 ± 13 mmHg to 100 ± 17 mmHg and 89 ± 10 bpm to 72 ± 10 bpm) exercise bouts. Together, these findings document that group III/IV muscle afferent feedback is critical for the resetting of the carotid baroreflex MAP and HR operating points, independent of exercise-induced changes in central command, but not for spontaneous carotid baroreflex responsiveness. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension

NASA Technical Reports Server (NTRS)

Fujimura, J.; Camilleri, M.; Low, P. A.; Novak, V.; Novak, P.; Opfer-Gehrking, T. L.

1997-01-01

Our aims were to evaluate to role of superior mesenteric blood flow in the pathophysiology of orthostatic hypotension in patients with generalized autonomic failure. METHODS: Twelve patients with symptomatic neurogenic orthostatic hypotension and 12 healthy controls underwent superior mesenteric artery flow measurements using Doppler ultrasonography during head-up tilt and tilt plus meal ingestion. Autonomic failure was assessed using standard tests of the function of the sympathetic adrenergic, cardiovagal and postganglionic sympathetic sudomotor function. RESULTS: Superior mesenteric flow volume and time-averaged velocity were similar in patients and controls at supine rest; however, responses to cold pressor test and upright tilt were attenuated (p < 0.05) in patients compared to controls. Head-up tilt after the meal evoked a profound fall of blood pressure and mesenteric blood flow in the patients; the reduction of mesenteric blood flow correlated (r = 0.89) with the fall of blood pressure in these patients, providing another manifestation of failed baroreflexes. We make the novel finding that the severity of postprandial orthostatic hypotension regressed negatively with the postprandial increase in mesenteric flow in patients with orthostatic hypotension. CONCLUSION: Mesenteric flow is under baroreflex control, which when defective, results in, or worsens orthostatic hypotension. Its large size and baroreflexivity renders it quantitatively important in the maintenance of postural normotension. The effects of orthostatic stress can be significantly attenuated by reducing the splanchnic-mesenteric volume increase in response to food. Evaluation of mesenteric flow in response to eating and head-up tilt provide important information on intra-abdominal sympathetic adrenergic function, and the ability of the patient to cope with orthostatic stress.

Regulation of sympathetic nervous system function after cardiovascular deconditioning

NASA Technical Reports Server (NTRS)

Hasser, E. M.; Moffitt, J. A.

2001-01-01

Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.

Effects of weightlessness on human baroreflex function

NASA Technical Reports Server (NTRS)

Fritsch, Janice M.; Eckberg, Dwain L.

1992-01-01

Impaired cardiovascular function, characterized by orthostatic intolerance and reduced exercise capacity, is a result of space travel. We hypothesized that postflight baroreflex dysfunction may contribute. We studied the vagally mediated carotid baroreceptor-cardiac reflex response of 6 astronauts before, during, and after the ten day SLS-l mission. A series of R-waves triggered pressure and suction steps (from 40 to minus 65 mmHg) were delivered to a neck chamber during held expirtation. Resulting R-R interval changes were plotted against carotid distending pressure (systolic - neck pressure), and curve parameters calculated. After an initial rise, the operational point declined consistently during the flight and reached a nadir on landing day, but had recovered to preflight levels by L + 4. Slope and range of the response declined throughout the flight, were slightly recovered by the time measurements were made on landing day, but still were reduced on L + 4. These data indicate that space flight results in a significant impairment of the carotid baroreceptor cardiac reflex response.

The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease.

PubMed

Yao, Yimin; Hildreth, Cara M; Farnham, Melissa M; Saha, Manash; Sun, Qi-Jian; Pilowsky, Paul M; Phillips, Jacqueline K

2015-06-01

The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined. Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT1R antagonist 3 mg/kg, intravenous). Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but not lSNA, was reduced. Losartan reduced MAP in both strains and selectively improved baroreflex gain for sSNA (-1.2 ± 0.1 vs. -0.7 ± 0.07 %/mmHg; P < 0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in Lewis controls, but reduced or had no effect on these parameters, respectively, in LPK. The SNA response to somatosensory stimulation was biphasic, with latency to second peak less in LPK. Losartan ameliorated the depressor and sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK, but did not alter the central chemoreflex or somatosympathetic responses. Inhibition of the AT1R selectively improved baroreflex control of sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows in the LPK rat, suggesting these anomalies in reflex function are driven in part by angiotensin II.

Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet.

PubMed

Abe, Chikara; Nagai, Yuko; Yamaguchi, Aoi; Aoki, Hitomi; Shimizu, Shuji; Akiyama, Tsuyoshi; Kawada, Toru; Sugimachi, Masaru; Morita, Hironobu

2015-04-15

Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats. Copyright © 2015 the American Physiological Society.

Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat.

PubMed

Johnson, Megan S; DeMarco, Vincent G; Heesch, Cheryl M; Whaley-Connell, Adam T; Schneider, Rebecca I; Rehmer, Nathan T; Tilmon, Roger D; Ferrario, Carlos M; Sowers, James R

2011-10-01

The aim of this investigation was to evaluate sex differences in baroreflex and heart rate variability (HRV) dysfunction and indexes of end-organ damage in the TG(mRen2)27 (Ren2) rat, a model of renin overexpression and tissue renin-angiotensin-aldosterone system overactivation. Blood pressure (via telemetric monitoring), blood pressure variability [BPV; SD of systolic blood pressure (SBP)], spontaneous baroreflex sensitivity, HRV [HRV Triangular Index (HRV-TI), standard deviation of the average NN interval (SDNN), low and high frequency power (LF and HF, respectively), and Poincaré plot analysis (SD1, SD2)], and cardiovascular function (pressure-volume loop analysis and proteinuria) were evaluated in male and female 10-wk-old Ren2 and Sprague Dawley rats. The severity of hypertension was greater in Ren2 males (R2-M) than in Ren2 females (R2-F). Increased BPV, suppression of baroreflex gain, decreased HRV, and associated end-organ damage manifested as cardiac dysfunction, myocardial remodeling, elevated proteinuria, and tissue oxidative stress were more pronounced in R2-M compared with R2-F. During the dark cycle, HRV-TI and SDNN were negatively correlated with SBP within R2-M and positively correlated within R2-F; within R2-M, these indexes were also negatively correlated with end-organ damage [left ventricular hypertrophy (LVH)]. Furthermore, within R2-M only, LVH was strongly correlated with indexes of HRV representing predominantly vagal (HF, SD1), but not sympathetic (LF, SD2), variability. These data demonstrated relative protection in females from autonomic dysfunction and end-organ damage associated with elevated blood pressure in the Ren2 model of hypertension.

Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury.

PubMed

Legg Ditterline, Bonnie E; Aslan, Sevda C; Randall, David C; Harkema, Susan J; Castillo, Camilo; Ovechkin, Alexander V

2018-03-01

To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI). Before-after intervention case-controlled clinical study. SCI research center and outpatient rehabilitation unit. Participants (N=44) consisted of persons with chronic SCI ranging from C2 to T11 who participated in RT (n=24), and untrained control subjects with chronic SCI ranging from C2 to T9 (n=20). A total of 21±2 RT sessions performed 5 days a week during a 4-week period using a combination of pressure threshold inspiratory and expiratory devices. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), and beat-to-beat arterial blood pressure and heart rate changes during the 5-second-long maximum expiratory pressure maneuver (5s MEP) and the sit-up orthostatic stress test, acquired before and after the RT program. In contrast to the untrained controls, individuals in the RT group experienced significantly increased FVC and FEV 1 (both P<.01) in association with improved quality of sleep, cough, and speech. Sympathetically (phase II) and parasympathetically (phase IV) mediated baroreflex sensitivity both significantly (P<.05) increased during the 5s MEP. During the orthostatic stress test, improved autonomic control over heart rate was associated with significantly increased sympathetic and parasympathetic modulation (low- and high-frequency change: P<.01 and P<.05, respectively). Inspiratory-expiratory pressure threshold RT is a promising technique to positively affect both respiratory and cardiovascular dysregulation observed in persons with chronic SCI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Changes in oestrogen receptor alpha expression in the nucleus of the solitary tract of the rat over the oestrous cycle and following ovariectomy.

PubMed

Spary, E J; Maqbool, A; Batten, T F C

2010-06-01

Oestrogen is capable of modulating autonomic outflow and baroreflex function via actions on groups of neurones in the brainstem. We investigated the presence of oestrogen receptor (ER) alpha in a part of the nucleus of the solitary tract (NTS) associated with central cardiovascular control, aiming to determine whether ERalpha mRNA and protein expression is correlated with levels of circulating oestrogen during the oestrous cycle. Polymerase chain reaction (PCR) detected ERalpha mRNA in the NTS at each stage of the oestrous cycle, from ovariectomised, sham-operated and male rats. Real-time PCR showed variations in ERalpha mRNA expression during the oestrous cycle, with the highest levels seen in oestrus, and lowest levels in metoestrus (P < 0.05 versus oestrus) and proestrus (P < 0.05 versus oestrus). Expression in males was lower than in dioestrus and oestrus females (P < 0.05). After ovariectomy, ERalpha mRNA levels were decreased compared to sham-operated animals (P < 0.01). Confocal fluorescence immunohistochemistry with stereological analysis showed that numbers of ERalpha immunoreactive cell nuclei per mm(3) of tissue in the caudal NTS were significantly greater in proestrus than in other groups of rats (P < 0.05). There were also differences among the groups in the extent of colocalisation of ERalpha in neurones immunoreactive for tyrosine hydroxylase and nitric oxide synthase. These results imply a complex pattern of region-specific oestrogen signalling in the NTS and suggest that ERalpha expression in this important autonomic nucleus may be related to circulating oestrogen levels. This may have consequences for the regulation of autonomic tone and baroreflex sensitivity when oestrogen levels decline, for example following menopause.

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats.

PubMed

Almeida, Jeferson; Duarte, Josiane O; Oliveira, Leandro A; Crestani, Carlos C

2015-01-01

Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

Factor analytic reduction of the carotid-cardiac baroreflex parameters

NASA Technical Reports Server (NTRS)

Ludwig, David A.

1989-01-01

An accepted method for measuring the responsiveness of the carotid-cardiac baroreflex to arterial pressure changes is to artificially stimulate the baroreceptors in the neck. This is accomplished by using a pressurized neck cuff which constricts and distends the carotid artery and subsequently stimulates the baroreceptors. Nine physiological responses to this type of stimulation are quantified and used as indicators of the baroreflex. Thirty male humans between the ages 27 and 46 underwent the carotid-cardiac baroreflex test. The data for the nine response parameters were analyzed by principle component factor analysis. The results of this analysis indicated that 93 percent of the total variance across all nine parameters could be explained in four dimensions. Examination of the factor loadings following an orthogonal rotation of the principle components indicated four well defined dimensions. The first two dimensions reflected location points for R-R interval and carotid distending pressure respectively. The third dimension was composed of measures reflecting the gain of the reflex. The fourth dimension was the ratio of the resting R-R interval to R-R interval during simulated hypertension. The data suggests that the analysis of all nine baroreflex parameters is redundant.

Effect of endogenous angiotensin II on renal nerve activity and its cardiac baroreflex regulation.

PubMed

Dibona, G F; Jones, S Y; Sawin, L L

1998-11-01

The effects of physiologic alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity and its cardiac baroreflex regulation were studied. The effect of angiotensin II type 1 receptor blockade with intracerebroventricular losartan was examined in conscious rats consuming a low, normal, or high sodium diet that were instrumented for the simultaneous measurement of right atrial pressure and renal sympathetic nerve activity. The gain of cardiac baroreflex regulation of renal sympathetic nerve activity (% delta renal sympathetic nerve activity/mmHg mean right atrial pressure) was measured during isotonic saline volume loading. Intracerebroventricular losartan did not decrease arterial pressure but significantly decreased renal sympathetic nerve activity in low (-36+/-6%) and normal (-24+/-5%), but not in high (-2+/-3%) sodium diet rats. Compared with vehicle treatment, losartan treatment significantly increased cardiac baroreflex gain in low (-3.45+/-0.20 versus -2.89+/-0.17) and normal (-2.89+/-0.18 versus -2.54+/-0.14), but not in high (-2.27+/-0.15 versus -2.22+/-0.14) sodium diet rats. These results indicate that physiologic alterations in endogenous angiotensin II activity tonically influence basal levels of renal sympathetic nerve activity and its cardiac baroreflex regulation.

Nonlinear identification of the total baroreflex arc: chronic hypertension model.

PubMed

Moslehpour, Mohsen; Kawada, Toru; Sunagawa, Kenji; Sugimachi, Masaru; Mukkamala, Ramakrishna

2016-05-01

The total baroreflex arc is the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP). Its linear dynamic functioning has been shown to be preserved in spontaneously hypertensive rats (SHR). However, the system is known to exhibit nonlinear dynamic behaviors. The aim of this study was to establish nonlinear dynamic models of the total arc (and its subsystems) in hypertensive rats and to compare these models with previously published models for normotensive rats. Hypertensive rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned. The carotid sinus regions were isolated and attached to a servo-controlled piston pump. AP and sympathetic nerve activity were measured while CSP was controlled via the pump using Gaussian white noise stimulation. Second-order, nonlinear dynamics models were developed by application of nonparametric system identification to a portion of the measurements. The models of the total arc predicted AP 21-43% better (P < 0.005) than conventional linear dynamic models in response to a new portion of the CSP measurement. The linear and nonlinear terms of these validated models were compared with the corresponding terms of an analogous model for normotensive rats. The nonlinear gains for the hypertensive rats were significantly larger than those for the normotensive rats [-0.38 ± 0.04 (unitless) vs. -0.22 ± 0.03, P < 0.01], whereas the linear gains were similar. Hence, nonlinear dynamic functioning of the sympathetically mediated total arc may enhance baroreflex buffering of AP increases more in SHR than normotensive rats. Copyright © 2016 the American Physiological Society.

Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats.

PubMed

Giusti, Marcelo Franchini; Sato, Monica Akemi; Cardoso, Leonardo Máximo; Braga, Valdir Andrade; Colombari, Eduardo

2011-02-04

Baroreceptor reflex is an important system for neural control of blood pressure. Recently, reactive oxygen species (ROS) have been shown to play an important role in neuronal activity of central areas related to blood pressure control. The aim of this study was to investigate the effects elicited by ascorbic acid (AAC) and N-acetylcysteine (NAC) injections into the 4thV on the parasympathetic component of the baroreflex. Male Wistar rats were implanted with a stainless steel guide cannula into the 4thV. One day prior to the experiments, the femoral artery and vein were cannulated for pulsatile arterial pressure, mean arterial pressure and heart rate measurements and drug administration, respectively. After baseline recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 3 μg/kg, i.v.) and a depressor dose of sodium nitroprusside (SNP, 30 μg/kg, i.v.) before (control) and 5, 15, 30 and 60 min after AAC or NAC into the 4thV. Control PHE injection induced baroreflex-mediated bradycardia (-93 ± 13 bpm, n=7). Interestingly, after AAC injection into the 4thV, PHE injection produced a transient tachycardia at 5 (40 ± 23 bpm), 15 (26 ± 22 bpm) and 30 min (59 ± 21 bpm). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after AAC injection on 4thV (control: 151 ± 23bpm vs. 135 ± 18 bpm at 5 min after AAC, n=7). In the NAC treated group, PHE induced a reduction in reflex bradycardia at 5 min when compared to control (-11 ± 17 bpm vs. -83 ± 15 bpm, n=7). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after NAC injection on 4thV. The antioxidants AAC and NAC may act in the central nervous system affecting the parasympathetic component of the cardiac baroreflex. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension.

PubMed

Li, Changjun; Chang, Qinghua; Zhang, Jia; Chai, Wenshu

2018-05-01

This study is to investigate the effects of slow breathing on heart rate variability (HRV) and arterial baroreflex sensitivity in essential hypertension.We studied 60 patients with essential hypertension and 60 healthy controls. All subjects underwent controlled breathing at 8 and 16 breaths per minute. Electrocardiogram, respiratory, and blood pressure signals were recorded simultaneously. We studied effects of slow breathing on heart rate, blood pressure and respiratory peak, high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio of HRV with traditional and corrected spectral analysis. Besides, we tested whether slow breathing was capable of modifying baroreflex sensitivity in hypertensive subjects.Slow breathing, compared with 16 breaths per minute, decreased the heart rate and blood pressure (all P < .05), and shifted respiratory peak toward left (P < .05). Compared to 16 breaths/minute, traditional spectral analysis showed increased LF power and LF/HF ratio, decreased HF power of HRV at 8 breaths per minute (P < .05). As breathing rate decreased, corrected spectral analysis showed increased HF power, decreased LF power, LF/HF ratio of HRV (P < .05). Compared to controls, resting baroreflex sensitivity decreased in hypertensive subjects. Slow breathing increased baroreflex sensitivity in hypertensive subjects (from 59.48 ± 6.39 to 78.93 ± 5.04 ms/mm Hg, P < .05) and controls (from 88.49 ± 6.01 to 112.91 ± 7.29 ms/mm Hg, P < .05).Slow breathing can increase HF power and decrease LF power and LF/HF ratio in essential hypertension. Besides, slow breathing increased baroreflex sensitivity in hypertensive subjects. These demonstrate slow breathing is indeed capable of shifting sympatho-vagal balance toward vagal activities and increasing baroreflex sensitivity, suggesting a safe, therapeutic approach for essential hypertension.

Uncoupling of the baroreflex by N(N)-cholinergic blockade in dissecting the components of cardiovascular regulation

NASA Technical Reports Server (NTRS)

Shannon, J. R.; Jordan, J.; Black, B. K.; Costa, F.; Robertson, D.

1998-01-01

Systemic administration of adrenergic agonists and nitric oxide donors is used extensively to determine cardiovascular receptor sensitivity. Conclusions regarding receptor sensitivity in the presence of the baroreflex may be misleading. In 8 normal volunteers, we determined the heart rate and blood pressure changes after incremental bolus doses of isoproterenol, phenylephrine, and sodium nitroprusside before and during neuronal nicotinic cholinergic (N(N)-cholinergic) blockade with trimethaphan. Results are given as median (25th/75th percentile). With trimethaphan, the baroreflex slope (as determined by bolus doses of nitroprusside and phenylephrine) decreased from 24 (22/26) to 0.00 (0.00/0.09) ms/mm Hg (P<0.01). The dose of isoproterenol that decreased systolic blood pressure (SBP) 12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) microg (P<0.01); the dose required to increase heart rate 12.5 bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) microg (P<0.01). The dose of nitroprusside required to decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18 (0.14/0.24) microg/kg (P<0.01). The dose of phenylephrine required to increase SBP 12.5 mm Hg changed from 135 (110/200) to 16 (10/30) microg (P<0.01). We conclude that the efferent arc of the baroreflex can be completely interrupted with N(N)-cholinergic blockade. Estimation of adrenoreceptor sensitivity and sensitivity to nitric oxide donors by systemic administration of agonists is severely confounded by baroreflexes. Uncoupling of the baroreflex by N(N)-cholinergic blockade may be a useful method to obtain an integrated measure of adrenergic receptor sensitivity and sensitivity to nitric oxide donors in humans. This approach would permit the comparison of normal and abnormal physiological states without the "noise" of baroreflex buffering.

Respiratory modulation of human autonomic function: long-term neuroplasticity in space.

PubMed

Eckberg, Dwain L; Diedrich, André; Cooke, William H; Biaggioni, Italo; Buckey, Jay C; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Kuusela, Tom A; Tahvanainen, Kari U O; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J; Levine, Benjamin D; Adams-Huet, Beverley; Robertson, David; Blomqvist, C Gunnar

2016-10-01

We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance. Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity. Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth. Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts' abilities to modulate both burst areas and frequencies during apnoea were sharply diminished. Spaceflight triggers long-term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes. We studied six healthy astronauts five times, on Earth, in space on the first and 12th or 13th day of the 16 day Neurolab Space Shuttle mission, on landing day, and 5-6 days later. Astronauts followed a fixed protocol comprising controlled and random frequency breathing and apnoea, conceived to perturb their autonomic function and identify changes, if any, provoked by microgravity exposure. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations and volumes, and peroneal nerve muscle sympathetic activity on Earth (in the supine position) and in space. (Sympathetic nerve recordings were made during three sessions: preflight, late mission and landing day.) Arterial pressure changed systematically from preflight levels: pressure fell during early microgravity exposure, rose as microgravity exposure continued, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations (root mean square of successive normal R-R intervals; and proportion of successive normal R-R intervals greater than 50 ms, divided by the total number of normal R-R intervals) rose significantly during early microgravity exposure, fell as microgravity exposure continued, and descended to preflight levels upon return to Earth. Sympathetic mechanisms also changed. Burst frequencies (but not areas) during fixed frequency breathing were greater than preflight in space and on landing day, but their control during apnoea was sharply altered: astronauts increased their burst frequencies from already high levels, but they could not modulate either burst areas or frequencies appropriately. Space travel provokes long-lasting sympathetic and vagal neuroplastic changes in healthy humans. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Bed Rest Affects Ventricular and Arterial Elastances in Monkeys: Implications for Humans

DTIC Science & Technology

2004-01-01

Eart may provide insight into adaptation and compromise of cardiovascular function induced by exposure to microgravity or confinement to bed rest...control treatments in our animals in order for Ees to increase in a similar magnitude across LBNP. Although we did not measure cardiac baroreflex function ...treatments. Sunagawa and co-workers have proposed that the integrity of cardiovascular function during rest and exercise is dependent on a mechanical

Behavioral neurocardiac training in hypertension: a randomized, controlled trial.

PubMed

Nolan, Robert P; Floras, John S; Harvey, Paula J; Kamath, Markad V; Picton, Peter E; Chessex, Caroline; Hiscock, Natalie; Powell, Jonathan; Catt, Michael; Hendrickx, Hilde; Talbot, Duncan; Chen, Maggie H

2010-04-01

It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks ("mental stress"). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (-2.4+/-0.9 mm Hg, P=0.009, and -2.1+/-0.9 mm Hg, P=0.03, respectively) and pulse pressures (-1.7+/-0.6 mm Hg, P=0.004, and -1.4+/-0.6 mm Hg, P=0.02, respectively). No effect was observed for controls (P>0.10 for all indices). BNT also increased RR-high-frequency power (0.15 to 0.40 Hz; P=0.01) and RR interval (P<0.001) during cognitive tasks. Among controls, high-frequency power was unchanged (P=0.29), and RR interval decreased (P=0.03). Neither intervention altered spontaneous baroreflex sensitivity (P>0.10). In contrast to relaxation therapy, BNT with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain. BNT, alone or as an adjunct to drug therapy, may represent a promising new intervention for hypertension.

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia.

PubMed

Ai, Jing; Wang, Li-Hong; Zhang, Rong; Qiao, Guo-Fen; Wang, Ning; Sun, Li-Hua; Lu, Guan-Yi; Sun, Chao; Yang, Bao-Feng

2010-12-22

The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia. Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats), and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP) and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP). Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM). The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR) in response to PE-induced hypertension (+ΔMABP) (P < 0.05). In the presence of SNP, DMC increased the ΔMABP (P < 0.05). In addition, DMC markedly shortened the duration of blood pressure changes elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05). Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of neuropathology were largely prevented by treatment with DMC for 30 days. Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM rats, but had no effect on GABAA receptor expression. The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

Externalizing and Internalizing Problems in Relation to Autonomic Function: A Population-Based Study in Preadolescents

ERIC Educational Resources Information Center

Dietrich, Andrea; Riese, Harriette; Sondeijker, Frouke E. P. L.; Greaves-Lord, Kirstin; van Roon, Arie M.; Ormel, Johan; Neeleman, Jan; Rosmalen, Judith G. M.

2007-01-01

Objective: To investigate whether externalizing and internalizing problems are related to lower and higher heart rate (HR), respectively, and to explore the relationship of these problems with respiratory sinus arrhythmia (RSA) and baroreflex sensitivity (BRS). Moreover, to study whether problems present at both preschool and preadolescent age…

Baroreflex dysfunction in sick newborns makes heart rate an unreliable surrogate for blood pressure changes.

PubMed

Govindan, Rathinaswamy B; Al-Shargabi, Tareq; Massaro, An N; Metzler, Marina; Andescavage, Nickie N; Joshi, Radhika; Dave, Rhiya; du Plessis, Adre

2016-06-01

Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns. Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis. We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres. In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants.

Noninvasive identification of the total peripheral resistance baroreflex

NASA Technical Reports Server (NTRS)

Mukkamala, Ramakrishna; Toska, Karin; Cohen, Richard J.

2003-01-01

We propose two identification algorithms for quantitating the total peripheral resistance (TPR) baroreflex, an important contributor to short-term arterial blood pressure (ABP) regulation. Each algorithm analyzes beat-to-beat fluctuations in ABP and cardiac output, which may both be obtained noninvasively in humans. For a theoretical evaluation, we applied both algorithms to a realistic cardiovascular model. The results contrasted with only one of the algorithms proving to be reliable. This algorithm was able to track changes in the static gains of both the arterial and cardiopulmonary TPR baroreflex. We then applied both algorithms to a preliminary set of human data and obtained contrasting results much like those obtained from the cardiovascular model, thereby making the theoretical evaluation results more meaningful. This study suggests that, with experimental testing, the reliable identification algorithm may provide a powerful, noninvasive means for quantitating the TPR baroreflex. This study also provides an example of the role that models can play in the development and initial evaluation of algorithms aimed at quantitating important physiological mechanisms.

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

PubMed Central

Arnold, Amy C.; Shaltout, Hossam A.; Gilliam-Davis, Shea; Kock, Nancy D.

2011-01-01

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II. PMID:21460193

Sympathetic baroreflex gain in normotensive pregnant women

PubMed Central

Usselman, Charlotte W.; Skow, Rachel J.; Matenchuk, Brittany A.; Chari, Radha S.; Julian, Colleen G.; Stickland, Michael K.; Davenport, Margie H.

2015-01-01

Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m2) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m2). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (−3.7 ± 0.5 vs. −5.4 ± 0.5 bursts·100 heart beats−1·mmHg−1, P = 0.03), as was baroreflex gain calculated with total sympathetic activity (−294 ± 24 vs. −210 ± 24 au·100 heart beats−1·mmHg−1; P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = −0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism. PMID:26139215

Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

PubMed Central

Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

2014-01-01

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

Characterisation of baroreflex sensitivity of recreational ultra-endurance athletes.

PubMed

Foulds, Heather J A; Cote, Anita T; Phillips, Aaron A; Charlesworth, Sarah A; Bredin, Shannon S D; Burr, Jamie F; Drury, Chipman Taylor; Ngai, Shirley; Fougere, Renee J; Ivey, Adam C; Warburton, Darren E R

2014-01-01

Altered autonomic function has been identified following ultra-endurance event participation among elite world-class athletes. Despite dramatic increases in recreational athlete participation in these ultra-endurance events, the physiological effects on these athletes are less known. This investigation sought to characterise changes in surrogate measures of autonomic function: heart rate variability (HRV), blood pressure variability (BPV) and baroreceptor sensitivity (BRS) following ultra-endurance race participation. Further, we sought to compare baseline measures among ultra-endurance athletes and recreationally active controls not participating in the ultra-endurance race. Recreational ultra-endurance athletes (n = 25, 44.6 ± 8.2 years, 8 females) and recreationally active age, sex and body mass index matched controls (n = 25) were evaluated. Measurements of HRV, BPV and BRS were collected pre- and post-race for recreational ultra-endurance athletes and at baseline, for recreationally active controls. Post-race, ultra-endurance athletes demonstrated significantly greater sympathetic modulation [low frequency (LF) power HRV: 50.3 ± 21.6 normalised units (n.u.) to 65.9 ± 20.4 n.u., p = 0.01] and significantly lower parasympathetic modulation [high frequency (HF) power HRV: 45.0 ± 22.4 n.u. to 23.9 ± 13.1 n.u., p < 0.001] and BRS. Baseline measurements BRS (spectral: 13.96 ± 10.82 ms·mmHg(-1) vs. 11.39 ± 5.33 ms·mmHg(-1)) were similar among recreational ultra-endurance athletes and recreationally active controls, though recreational ultra-endurance athletes demonstrated greater parasympathetic modulation of some HRV and BPV measures. Recreational ultra-endurance athletes experienced increased sympathetic tone and declines in BRS post-race, similar to previously reported elite world-class ultra-endurance athletes, though still within normal population ranges.

Heart rate monitoring and control in altered gravity conditions.

PubMed

Di Rienzo, M; Parati, G; Rizzo, F; Meriggi, P; Merati, G; Faini, A; Castiglioni, P

2007-01-01

On the basis of indirect evidences it has been hypothesized that during space missions the almost complete absence of gravity might impair the baroreflex control of circulation. In the first part of this paper we report results obtained from a series of experiments carried out to directly verify this hypothesis during the 16-day STS 107 Shuttle flight. Spontaneous baroreflex sensitivity was assessed in four astronauts before flight (baseline) and at days 0-1, 6-7 and 12-13 during flight, both at rest and while performing moderate exercise. Our results indicate that at rest the baroreflex sensitivity significantly increased in the early flight phase, as compared to pre-flight values and tended to return to baseline in the mid-late phase of flight. During exercise, baroreflex sensitivity was lower than at rest, without any difference among pre-flight and in-flight values. These findings seem to exclude the hypothesis of an impairment of the baroreflex control of heart rate during exposure to microgravity, at least over a time window of 16 days. In the second part of the paper we propose a novel textile-based methodology for heart rate and other vital signs monitoring during gravity stress. The positive results obtained from its use during parachute jumps support the use of smart garments for the unobtrusive assessment of physiological parameters in extreme environments.

Baroreflex Impairment After Subarachnoid Hemorrhage Is Associated With Unfavorable Outcome.

PubMed

Nasr, Nathalie; Gaio, Rita; Czosnyka, Marek; Budohoski, Karol; Liu, Xiuyun; Donnelly, Joseph; Sykora, Marek; Kirkpatrick, Peter; Pavy-Le Traon, Anne; Haubrich, Christina; Larrue, Vincent; Smielewski, Peter

2018-07-01

Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving β-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. Forty-eight patients were included. Median age was 58 years old (36-76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS ( P =0.007), sedation ( P =0.001), World Federation of Neurosurgery score ( P =0.001), Glasgow score ( P =0.002), Fisher score ( P =0.022), and heart rate ( P =0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048-1.818; P =0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171-0.706; P =0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study. © 2018 American Heart Association, Inc.

Reduced baroreflex sensitivity with volume loading in conscious dogs

NASA Technical Reports Server (NTRS)

Vatner, S. F.; Boettcher, D. H.; Heyndrickx, G. R.; Mcritchie, R. J.

1975-01-01

Results of studies of the Bainbridge reflex in intact conscious dogs are presented. They indicate that arterial baroreflex sensitivity is reduced progressively as atrial pressure is raised by volume loading; this observation explains how heart rate can rise markedly in the presence of an elevated arterial blood pressure.

Acute effects on cardiovascular oscillations during controlled slow yogic breathing.

PubMed

Bhagat, Om Lata; Kharya, Chhaya; Jaryal, Ashok; Deepak, Kishore Kumar

2017-04-01

Breathing exercises are believed to modulate the cardiovascular oscillations in the body. To assess the validity of the assumption and understand the underlying mechanism, the key autonomic regulatory parameters such as heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were recorded during controlled slow yogic breathing. Alternate nostril breathing (ANB) was selected as the yogic manoeuvre. Twelve healthy volunteers (age 30±3.8 yr) participated in the study. ANB was performed at a breathing frequency of 5 breaths per minute (bpm). In each participant, the electrocardiogram, respiratory movements, beat-to-beat BP and end-tidal carbon dioxide were recorded for five minutes each: before, during and after ANB. The records were analyzed for HRV, BPV and BRS. During ANB, HRV analysis showed significant increase in the standard deviation of all NN intervals, low-frequency (LF) component, LF/HF (low frequency/high frequency) ratio and significant decrease in the HF component. BPV analysis showed a significant increase in total power in systolic BPV (SBPV), diastolic BPV (DBPV) and mean BPV. BRS analysis showed a significant increase in the total number of sequences in SBPV and DBPV and significant augmentation of α-LF and reduction in α-HF. The power spectrum showed a dominant peak in HRV at 0.08 Hz (LF component) similar to the respiratory frequency. The acute short-term change in circulatory control system declined immediately after the cessation of slow yogic breathing (ANB) and remained elevated in post-ANB stage as compared to the pre-ANB. Significant increase in cardiovascular oscillations and baroreflex recruitments during-ANB suggested a dynamic interaction between respiratory and cardiovascular system. Enhanced phasic relationship with some delay indicated the complexity of the system. It indicated that respiratory and cardiovascular oscillations were coupled through multiple regulatory mechanisms, such as mechanical coupling, baroreflex and central cardiovascular control.

Winter metabolic depression does not change arterial baroreflex control of heart rate in the tegu lizard Salvator merianae.

PubMed

Zena, Lucas A; Dantonio, Valter; Gargaglioni, Luciane H; Andrade, Denis V; Abe, Augusto S; Bícego, Kênia C

2016-03-01

Baroreflex regulation of blood pressure is important for maintaining appropriate tissue perfusion. Although temperature affects heart rate (fH) reflex regulation in some reptiles and toads, no data are available on the influence of temperature-independent metabolic states on baroreflex. The South American tegu lizard Salvator merianae exhibits a clear seasonal cycle of activity decreasing fH along with winter metabolic downregulation, independent of body temperature. Through pharmacological interventions (phenylephrine and sodium nitroprusside), the baroreflex control of fH was studied at ∼ 25 °C in spring-summer- and winter-acclimated tegus. In winter lizards, resting and minimum fH were lower than in spring-summer animals (respectively, 13.3 ± 0.82 versus 10.3 ± 0.81 and 11.2 ± 0.65 versus 7.97 ± 0.88 beats min(-1)), while no acclimation differences occurred in resting blood pressure (5.14 ± 0.38 versus 5.06 ± 0.56 kPa), baroreflex gain (94.3 ± 10.7 versus 138.7 ± 30.3% kPa(-1)) or rate-pressure product (an index of myocardial activity). Vagal tone exceeded the sympathetic tone of fH, especially in the winter group. Therefore, despite the lower fH, winter acclimation does not diminish the fH baroreflex responses or rate-pressure product, possibly because of increased stroke volume that may arise because of heart hypertrophy. Independent of acclimation, fH responded more to hypotension than to hypertension. This should imply that tegus, which have no pressure separation within the single heart ventricle, must have other protection mechanisms against pulmonary hypertension or oedema, presumably through lymphatic drainage and/or vagal vasoconstriction of pulmonary artery. Such a predominant fH reflex response to hypotension, previously observed in anurans, crocodilians and mammals, may be a common feature of tetrapods. © 2016. Published by The Company of Biologists Ltd.

Baroreflex-mediated heart rate and vascular resistance responses 24 h after maximal exercise

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

2003-01-01

INTRODUCTION: Plasma volume, heart rate (HR) variability, and stimulus-response relationships for baroreflex control of forearm vascular resistance (FVR) and HR were studied in eight healthy men after and without performing a bout of maximal exercise to test the hypotheses that acute expansion of plasma volume is associated with 1) reduction in baroreflex-mediated HR response, and 2) altered operational range for central venous pressure (CVP). METHODS: The relationship between stimulus (DeltaCVP) and vasoconstrictive reflex response (DeltaFVR) during unloading of cardiopulmonary baroreceptors was assessed with lower-body negative pressure (LBNP, 0, -5, -10, -15, -20 mm Hg). The relationship between stimulus (Deltamean arterial pressure (MAP)) and cardiac reflex response (DeltaHR) during loading of arterial baroreceptors was assessed with steady-state infusion of phenylephrine (PE) designed to increase MAP by 15 mm Hg alone and during application of LBNP (PE+LBNP) and neck pressure (PE+LBNP+NP). Measurements of vascular volume and autonomic baroreflex responses were conducted on two different test days, each separated by at least 1 wk. On one day, baroreflex response was tested 24 h after graded cycle exercise to volitional exhaustion. On another day, measurement of baroreflex response was repeated with no exercise (control). The order of exercise and control treatments was counterbalanced. RESULTS: Baseline CVP was elevated (P = 0.04) from a control value of 10.5 +/- 0.4 to 12.3 +/- 0.4 mm Hg 24 h after exercise. Average DeltaFVR/DeltaCVP during LBNP was not different (P = 0.942) between the exercise (-1.35 +/- 0.32 pru x mm Hg-1) and control (-1.32 +/- 0.36 pru x mm Hg-1) conditions. However, maximal exercise caused a shift along the reflex response relationship to a higher CVP and lower FVR. HR baroreflex response (DeltaHR/DeltaMAP) to PE+LBNP+NP was lower (P = 0.015) after maximal exercise (-0.43 +/- 0.15 beats x min-1 x mm Hg-1) compared with the control condition (-0.83 +/- 0.14 beats x min-1 x mm Hg-1). CONCLUSION: Expansion of vascular volume after acute exercise is associated with altered operational range for CVP and reduced HR response to arterial baroreceptor stimulation.

Impact of space flight on cardiovascular autonomic control

NASA Astrophysics Data System (ADS)

Beckers, F.; Verheyden, B.; Morukov, B.; Aubert, Ae

Introduction: Space flight alters the distribution of blood in the human body, leading to altered cardiovascular neurohumoral regulation with a blunted carotid-cardiac baroreflex. These changes contribute to the occurrence of orthostatic intolerance after space flight. Heart rate variability (HRV) and blood pressure variability (BPV) provide non-invasive means to study the autonomic modulation of the heart. Low frequency (LF) oscillations provide information about sympathetic modulation and baroreflex, while high frequency (HF) modulation is an index of vagal heart rate modulation. Methods: ECG and continuous blood pressure were measured for at least 10 minutes in supine, sitting and standing position 45 days and 10 days (L-45, L-10) before launch; and at 1, 2, 4, 9, 15, 19 and 25 days after return to earth (R+x). In space, ECG and continuous blood pressure were measured at day 5 (FD5) and day 8 (FD8). These measurements were performed in 3. HRV and BPV indices were calculated in time and frequency domain. Results: Measurements in supine position and sitting position did not show as high differences as the measurements in standing position. During space flight heart rate was significantly lower compared to the pre- and post-flight measurements in standing position (RR-values: L-45: 837± 42 ms; FD5: 1004± 40 ms; FD8: 1038± 53 ms; R+1: 587± 21 ms; p<0.05). This was accompanied by a significant increase in the proportion of HF power during space flight and a decrease in LF power. Immediately after space flight both LF and HF modulation of heart rate were extremely depressed compared to the pre-flight conditions (p<0.005). A gradual recovery towards baseline conditions of both indices was observed up to 25 days after return from space (LF: L-45: 3297± 462 ms2; FD5: 1251± 332 ms2; FD8: 1322± 462 ms2; R+1: 547± 188 ms2; R+4: 1958± 709 ms2; R+9: 1220± 148 ms2; R+15: 1704± 497 ms2; R+25: 2644± 573 ms2). However, even 25 days after return, values were below baseline condition. Mean systolic blood pressure did not differ significantly before during and after space flight. In space both LF and HF were decreased compared the standing measurements pre- and post-flight. No evolution was present in BPV after return to Earth. Conclusion: During space flight autonomic modulation is characterised by a vagal predominance. Immediately after return to Earth overall autonomic modulation is extremely depressed. Vasomotor autonomic control is restored rather quickly after space flight, while the restoration of autonomic modulation of heart rate is very slow.

Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights.

PubMed

Grassi, Guido; Brambilla, GianMaria; Pizzalla, Daniela Prata; Seravalle, Gino

2016-08-01

Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.

Cardiorespiratory interactions in neural circulatory control in humans.

PubMed

Shamsuzzaman, A S; Somers, V K

2001-06-01

The reflex mechanisms and interactions described in this overview provide some explanation for the range of neural circulatory responses evident during changes in breathing. The effects described represent the integrated responses to activation of several reflex mechanisms, including peripheral and central chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and ventricular mechanoreceptors. These interactions occur on a dynamic basis and the transfer characteristics of any single interaction are, in all likelihood, also highly dynamic. Nevertheless, it is only by attempting to understand individual reflexes and their modulating influences that a more thorough understanding of the responses to complex phenomena such as hyperventilation, apnea, and obstructive sleep apnea can be better understood.

The Influence of Exercise Intensity on Postexercise Baroreflex Sensitivity

ERIC Educational Resources Information Center

Reynolds, Linda J.; De Ste Croix, Mark B. A.; James, David V. B.

2017-01-01

Purpose: The purpose of this study was to investigate the influence of exercise intensity on postexercise supine and tilt baroreflex sensitivity (BRS). Method: Nine healthy, active men performed 2 conditions of interval cycling of 40% maximal work rate (WR[subscript max]) and 75% WR[subscript max] of matched work done and a control condition of no…

Diagnosis and management of baroreflex failure

NASA Technical Reports Server (NTRS)

Robertson, D.

1995-01-01

Baroreflex failure has a range of presentations, varying from the acute onset of a hypertensive crisis to a chronically volatile blood pressure and heart rate with hypertensive surges in response to stress, punctuated by periods of normal or even low blood pressure during rest. Differentiating this syndrome from other causes of labile hypertension is essential in devising effective treatment.

A model-based approach for the evaluation of vagal and sympathetic activities in a newborn lamb.

PubMed

Le Rolle, Virginie; Ojeda, David; Beuchée, Alain; Praud, Jean-Paul; Pladys, Patrick; Hernández, Alfredo I

2013-01-01

This paper proposes a baroreflex model and a recursive identification method to estimate the time-varying vagal and sympathetic contributions to heart rate variability during autonomic maneuvers. The baroreflex model includes baroreceptors, cardiovascular control center, parasympathetic and sympathetic pathways. The gains of the global afferent sympathetic and vagal pathways are identified recursively. The method has been validated on data from newborn lambs, which have been acquired during the application of an autonomic maneuver, without medication and under beta-blockers. Results show a close match between experimental and simulated signals under both conditions. The vagal and sympathetic contributions have been simulated and, as expected, it is possible to observe different baroreflex responses under beta-blockers compared to baseline conditions.

Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

PubMed

Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

2016-02-01

Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Baroreflex activation therapy lowers arterial pressure without apparent stimulation of the carotid bodies.

PubMed

Alnima, Teba; Goedhart, Emilie J B M; Seelen, Randy; van der Grinten, Chris P M; de Leeuw, Peter W; Kroon, Abraham A

2015-06-01

Carotid baroreflex activation therapy produces a sustained fall in blood pressure in patients with resistant hypertension. Because the activation electrodes are implanted at the level of the carotid sinus, it is conceivable that the nearby located carotid body chemoreceptors are stimulated as well. Physiological stimulation of the carotid chemoreceptors not only stimulates respiration but also increases sympathetic activity, which may counteract the effects of baroreflex activation. The aim of this exploratory study is to investigate whether there is concomitant carotid chemoreflex activation during baroreflex activation therapy. Fifteen participants with the Rheos system were included in this single-center study. At arrival at the clinic, the device was switched off for 2 hours while patients were at rest. Subsequently, the device was switched on at 6 electric settings of high and low frequencies and amplitudes. Respiration and blood pressure measurements were performed during all device activation settings. Multilevel statistical models were adjusted for age, sex, body mass index, antihypertensive therapeutic index, sleep apnea, coronary artery disease, systolic blood pressure, and heart rate. There was no change in end-tidal carbon dioxide, partial pressure of carbon dioxide, breath duration, and breathing frequency during any of the electric settings with the device. Nevertheless, mean arterial pressure showed a highly significant decrease during electric activation (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not stimulate respiration at several electric device activation energies, which suggests that there is no appreciable coactivation of carotid body chemoreceptors during device therapy. © 2015 American Heart Association, Inc.

Interactions between CO2 chemoreflexes and arterial baroreflexes

NASA Technical Reports Server (NTRS)

Henry, R. A.; Lu, I. L.; Beightol, L. A.; Eckberg, D. L.

1998-01-01

We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication.

PubMed

Li, Faith C H; Yen, J C; Chan, Samuel H H; Chang, Alice Y W

2012-02-07

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

PubMed Central

2012-01-01

Background Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. Methods The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Results Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. Conclusions We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse. PMID:22313577

Impaired carotid baroreflex control of arterial blood pressure in multiple sclerosis.

PubMed

Huang, Mu; Allen, Dustin R; Keller, David M; Fadel, Paul J; Frohman, Elliot M; Davis, Scott L

2016-07-01

Multiple sclerosis (MS), a progressive neurological disease, can lead to impairments in the autonomic control of cardiovascular function. We tested the hypothesis that individuals with relapsing-remitting MS (n = 10; 7 females, 3 males; 13 ± 4 yr from diagnosis) exhibit impaired carotid baroreflex control of blood pressure and heart rate compared with sex, age, and body weight-matched healthy individuals (CON: n = 10; 7 females, 3 males). At rest, 5-s trials of neck pressure (NP; +40 Torr) and neck suction (NS; -60 Torr) were applied to simulate carotid hypotension and hypertension, respectively, while mean arterial pressure (MAP; finger photoplethysmography), heart rate (HR), cardiac output (CO; Modelflow), and total vascular conductance (TVC) were continuously measured. In response to NP, there was a blunted increase in peak MAP responses (MS: 5 ± 2 mmHg) in individuals with MS compared with healthy controls (CON: 9 ± 3 mmHg; P = 0.005), whereas peak HR responses were not different between groups. At the peak MAP response to NP, individuals with MS demonstrated an attenuated decrease in TVC (MS, -10 ± 4% baseline vs. CON, -15 ± 4% baseline, P = 0.012), whereas changes in CO were similar between groups. Following NS, all cardiovascular responses (i.e., nadir MAP and HR and percent changes in CO and TVC) were not different between MS and CON groups. These data suggest that individuals with MS have impaired carotid baroreflex control of blood pressure via a blunted vascular conductance response resulting in a diminished ability to increase MAP in response to a hypotensive challenge. Copyright © 2016 the American Physiological Society.

Evidence for cardiovascular autonomic dysfunction in neonates with coarctation of the aorta.

PubMed

Polson, Jaimie W; McCallion, Naomi; Waki, Hidefumi; Thorne, Gareth; Tooley, Mark A; Paton, Julian F R; Wolf, Andrew R

2006-06-20

Coarctation of the aorta (CoA) is associated with hypertension and abnormalities of blood pressure control, which persist after late repair. Assumptions that neonatal repair would prevent development of blood pressure abnormalities have not been supported by recent data. We hypothesized that early pathological adjustment of autonomic cardiovascular function may already be established in the neonate with coarctation. We studied 8 otherwise well neonates with simple CoA and compared measures of spontaneous baroreflex sensitivity, heart rate variability, and blood pressure variability with 13 healthy newborn babies. Spontaneous baroreflex sensitivity was calculated with sequence methodology from an ECG, and noninvasive blood pressure was recorded with a Portapres. Heart rate variability was determined with time- and frequency-domain measures. Blood pressure variability was measured in the frequency domain. In comparison with normal controls, neonates with CoA had raised blood pressure (78.9+/-3.8 versus 67.1+/-2.1 mm Hg), depressed baroreflex sensitivity (8.7+/-1.5 versus 13.8+/-1.1 ms/mm Hg), reduced heart rate variability (total power 16.5+/-3.1 versus 31.5+/-2.2 ms2), and an increase in the high-frequency component of blood pressure variability (3.1+/-0.3 versus 2.2+/-0. 2 mm Hg2). This is not the pattern expected if neonates with CoA simply had subclinical cardiac failure. These data suggest that infants with CoA already show signs of pathological adjustment of autonomic cardiovascular homeostasis. Further longitudinal studies are required to determine whether these alterations play a role in the increased risk of late hypertension in these patients.

Impaired carotid baroreflex control of arterial blood pressure in multiple sclerosis

PubMed Central

Huang, Mu; Allen, Dustin R.; Keller, David M.; Fadel, Paul J.; Frohman, Elliot M.

2016-01-01

Multiple sclerosis (MS), a progressive neurological disease, can lead to impairments in the autonomic control of cardiovascular function. We tested the hypothesis that individuals with relapsing-remitting MS (n = 10; 7 females, 3 males; 13 ± 4 yr from diagnosis) exhibit impaired carotid baroreflex control of blood pressure and heart rate compared with sex, age, and body weight-matched healthy individuals (CON: n = 10; 7 females, 3 males). At rest, 5-s trials of neck pressure (NP; +40 Torr) and neck suction (NS; −60 Torr) were applied to simulate carotid hypotension and hypertension, respectively, while mean arterial pressure (MAP; finger photoplethysmography), heart rate (HR), cardiac output (CO; Modelflow), and total vascular conductance (TVC) were continuously measured. In response to NP, there was a blunted increase in peak MAP responses (MS: 5 ± 2 mmHg) in individuals with MS compared with healthy controls (CON: 9 ± 3 mmHg; P = 0.005), whereas peak HR responses were not different between groups. At the peak MAP response to NP, individuals with MS demonstrated an attenuated decrease in TVC (MS, −10 ± 4% baseline vs. CON, −15 ± 4% baseline, P = 0.012), whereas changes in CO were similar between groups. Following NS, all cardiovascular responses (i.e., nadir MAP and HR and percent changes in CO and TVC) were not different between MS and CON groups. These data suggest that individuals with MS have impaired carotid baroreflex control of blood pressure via a blunted vascular conductance response resulting in a diminished ability to increase MAP in response to a hypotensive challenge. PMID:27075533

Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

PubMed

Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

2016-05-01

The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

PubMed

Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

2016-08-01

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. © 2016 American Heart Association, Inc.

Global- and renal-specific sympathoinhibition in aldosterone hypertension.

PubMed

Lohmeier, Thomas E; Liu, Boshen; Hildebrandt, Drew A; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

2015-06-01

Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 μg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. © 2015 American Heart Association, Inc.

Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation.

PubMed

Khan, S A; Sattar, M Z A; Abdullah, N A; Rathore, H A; Abdulla, M H; Ahmad, A; Johns, E J

2015-07-01

This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity. Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load. Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats. Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Global and Renal-Specific Sympathoinhibition in Aldosterone Hypertension

PubMed Central

Lohmeier, Thomas E.; Liu, Boshen; Hildebrandt, Drew A.; Cates, Adam W.; Georgakopoulos, Dimitrios; Irwin, Eric D.

2015-01-01

Recent technology for chronic electrical activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12µg/kg/day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ~ 40% and arterial pressure by 16±2 mmHg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mmHg) was diminished (~ 55%) during aldosterone hypertension as compared to control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. PMID:25895584

Influence of central venous pressure upon sinus node responses to arterial baroreflex stimulation in man

NASA Technical Reports Server (NTRS)

Mark, A. L.; Takeshita, A.; Eckberg, D. L.; Abboud, F. M.

1978-01-01

Measurements were made of sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower truck elevation. Variations of central venous pressure between 1.1 and 9.0 mm Hg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. The authors conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man.

Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism.

PubMed

Syamsunder, Avupati Naga; Pal, Pravati; Pal, Gopal Krushna; Kamalanathan, Chandrakasan Sadishkumar; Parija, Subhash Chandra; Nanda, Nivedita; Sirisha, Allampalli

2017-02-01

Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH.

Orthostatic intolerance and motion sickness after parabolic flight

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Brown, T. E.; Wood, S. J.; Benavides, E. W.; Bondar, R. L.; Stein, F.; Moradshahi, P.; Harm, D. L.; Fritsch-Yelle, J. M.; Low, P. A.

2001-01-01

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Affective brain areas and sleep disordered breathing

PubMed Central

Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Woo, Mary A.; Ogren, Jennifer A.

2014-01-01

The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing found in obstructive sleep apnea, heart failure (HF), and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude- distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, raphé, ventrolateral medulla, basal ganglia and, in CCHS, the locus coeruleus. Raphé and locus coeruleus injury may modify serotonergic and adrenergic modulation of upper airway and arousal characteristics. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several affected rostral sites, including the insular and cingulate cortices and hippocampus, mediate aspects of dyspnea, especially in CCHS, while others, including the anterior cingulate and thalamus, participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation. PMID:24746053

[Heart functions in monkeys during a 2-week antiorthostatic hypokinesia

NASA Technical Reports Server (NTRS)

Krotov, V. P.; Convertino, V.; Korol'kov, V. I.; Latham, R.; Trambovetskii, E. V.; Fanton, J.; Crisman, R.; Truzhennikov, A. N.; Evert, D.; Nosovskii, A. M.;

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial.

PubMed

Antonino, Diego; Teixeira, André L; Maia-Lopes, Paulo M; Souza, Mayara C; Sabino-Carvalho, Jeann L; Murray, Aaron R; Deuchars, Jim; Vianna, Lauro C

Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. Thirteen healthy men (23±1yrs) were randomized across three experimental visits. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time-control visit was performed with the electrodes placed on tragus, but no current was applied (sham-T). Additionally, to avoid a placebo effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus - tLS). Beat-to-beat heart rate (HR) and blood pressure (BP) were monitored at rest, during stimulation (active, sham-T and tLS) and recovery. cBRS was measured via sequence technique. Both HR (HRV) and BP variability (BPV) were also measured. Arterial BP and BPV were not affected by any active or sham protocols (P > 0.05). Resting HR and LF/HF ratio of HRV decreased (Δ-3.4 ± 1% and Δ-15 ± 12%, P < 0.05, respectively) and cBRS increased (Δ24 ± 8%, P < 0.05) during active tVNS, but were unchanged during both sham protocols. tVNS acutely improves cBRS and autonomic modulation in healthy young men. Copyright © 2017 Elsevier Inc. All rights reserved.

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

PubMed

Matsukawa, Kanji

2012-01-01

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

PubMed

Chalacheva, Patjanaporn; Kato, Roberta M; Sangkatumvong, Suvimol; Detterich, Jon; Bush, Adam; Wood, John C; Meiselman, Herbert; Coates, Thomas D; Khoo, Michael C K

2015-07-14

Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Blood pressure variability in man: its relation to high blood pressure, age and baroreflex sensitivity.

PubMed

Mancia, G; Ferrari, A; Gregorini, L; Parati, G; Pomidossi, G; Bertinieri, G; Grassi, G; Zanchetti, A

1980-12-01

1. Intra-arterial blood pressure and heart rate were recorded for 24 h in ambulant hospitalized patients of variable age who had normal blood pressure or essential hypertension. Mean 24 h values, standard deviations and variation coefficient were obtained as the averages of values separately analysed for 48 consecutive half-hour periods. 2. In older subjects standard deviation and variation coefficient for mean arterial pressure were greater than in younger subjects with similar pressure values, whereas standard deviation and variation coefficient for mean arterial pressure were greater than in younger subjects with similar pressure values, whereas standard deviation aations and variation coefficient were obtained as the averages of values separately analysed for 48 consecurive half-hour periods. 2. In older subjects standard deviation and variation coefficient for mean arterial pressure were greater than in younger subjects with similar pressure values, whereas standard deviation and variation coefficient for heart rate were smaller. 3. In hypertensive subjects standard deviation for mean arterial pressure was greater than in normotensive subjects of similar ages, but this was not the case for variation coefficient, which was slightly smaller in the former than in the latter group. Normotensive and hypertensive subjects showed no difference in standard deviation and variation coefficient for heart rate. 4. In both normotensive and hypertensive subjects standard deviation and even more so variation coefficient were slightly or not related to arterial baroreflex sensitivity as measured by various methods (phenylephrine, neck suction etc.). 5. It is concluded that blood pressure variability increases and heart rate variability decreases with age, but that changes in variability are not so obvious in hypertension. Also, differences in variability among subjects are only marginally explained by differences in baroreflex function.

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

PubMed

Pierce, G L; Harris, S A; Seals, D R; Casey, D P; Barlow, P B; Stauss, H M

2016-09-01

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=-0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Estimated Aortic Stiffness is Independently Associated with Cardiac Baroreflex Sensitivity in Humans: Role of Aging and Habitual Endurance Exercise

PubMed Central

Pierce, Gary L.; Harris, Stephen A.; Seals, Douglas R.; Casey, Darren P.; Barlow, Patrick B.; Stauss, Harald M.

2016-01-01

We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, P<0.001). The 8 week exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=−0.65, P=0.044, adjusted for changes in MAP). Age- and endurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise. PMID:26911535

Low arterial compliance in young African-American males.

PubMed

Zion, Adrienne S; Bond, Vernon; Adams, Richard G; Williams, Deborah; Fullilove, Robert E; Sloan, Richard P; Bartels, Matthew N; Downey, John A; De Meersman, Ronald E

2003-08-01

Hypertension remains a common public health challenge because of its prevalence and increase in co-morbid cardiovascular diseases. Black males have disproportionate pathophysiological consequences of hypertension compared with any other group in the United States. Alterations in arterial wall compliance and autonomic function often precede the onset of disease. Accordingly, our purpose was to investigate whether differences exist in arterial compliance and autonomic function between young, healthy African-American males without evidence of hypertension and age- and gender-matched non-African-American males. All procedures were carried out noninvasively following rest. Arterial compliance was calculated as the integrated area starting at the well-defined nadir of the incisura of the dicrotic notch to the end of diastole of the radial artery pulse wave. Power spectral analysis of heart rate and blood pressure variability provided distributions representative of parasympathetic and sympathetic modulations and sympathovagal balance. Baroreflex sensitivity (BRS) was calculated using the sequence method. Thirty-two African-American and twenty-nine non-African-American males were comparable in anthropometrics and negative family history of hypertension. t-Tests revealed lower arterial compliance (5.8 +/- 2.4 vs. 8.6 +/- 4.0 mmHg. s; P = 0.0017), parasympathetic modulation (8.9 +/- 1.1 vs. 9.7 +/- 1.1 ln ms2; P = 0.0063), and BRS (13.7 +/- 7.3 vs. 21.1 +/- 8.5 ms/mmHg; P = 0.0007) and higher sympathovagal balance (2.9 +/- 3.2 vs. 1.5 +/- 1.1; P = 0.03) in the African-American group. In summary, differences exist in arterial compliance and autonomic balance in African-American males. These alterations may be antecedent markers of disease and valuable in the detection of degenerative cardiovascular processes in individuals at risk.

Inspiratory Resistance Maintains Arterial Pressure During Central Hypovolemia: Implications For Treatment Of Combat Casualties With Severe Hemorrhage

DTIC Science & Technology

2006-11-01

negative pressure , thus drawing venous blood from extrathoracic cavities into the heart and lungs. We review here a series of experiments that demonstrate... blood pressure in normovolemia and hypovolemia; (b) increase cerebral blood flow velocity; (c) reset cardiac baroreflex function to a higher operating...range for blood pressure ; (d) lower intracranial pressure ; and (e) reduce orthostatic symptoms. In this brief review, we present evidence that

Effects of Repeated Valsalva Maneuver Straining on Cardiac and Vasoconstrictive Baroreflex Responses

DTIC Science & Technology

2003-03-01

of blood pressure regulation that differ in men repeatedly exposed to high G acceleration. Am J Physiol Regul Integr Comp Physiol 2001; 280:R947–58. 10...Methods: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures ), and changes in heart rate...hypothesis is the observation that elevated pulse pressures in isolated carotid sinuses of dogs sen- sitized baroreceptor afferent firing (4,5). Elevated arte

Haemodynamic changes during neck pressure and suction in seated and supine positions

NASA Technical Reports Server (NTRS)

Ogoh, S.; Fadel, P. J.; Monteiro, F.; Wasmund, W. L.; Raven, P. B.

2002-01-01

We sought to quantify the contribution of cardiac output (Q) and total vascular conductance (TVC) to carotid baroreflex-mediated changes in mean arterial pressure (MAP) in the upright seated and supine positions. Acute changes in carotid sinus transmural pressure were evoked using brief 5 s pulses of neck pressure and neck suction (NP/NS) via a simplified paired neck chamber that was developed to enable beat-to-beat measurements of stroke volume using pulse-doppler ultrasound. Percentage contributions of Q and TVC were achieved by calculating the predicted change in MAP during carotid baroreflex stimulation if only the individual changes in Q or TVC occurred and all other parameters remained at control values. All NP and NS stimuli from +40 to -80 Torr (+5.33 to -10.67 kPa) induced significant changes in Q and TVC in both the upright seated and supine positions (P < 0.001). Cardiopulmonary baroreceptor loading with the supine position appeared to cause a greater reliance on carotid baroreflex-mediated changes in Q. Nevertheless, in both the seated and supine positions the changes in MAP were primarily mediated by alterations in TVC (percentage contribution of TVC at the time-of-peak MAP, seated 95 +/- 13, supine 76 +/- 17 %). These data indicate that alterations in vasomotor activity are the primary means by which the carotid baroreflex regulates blood pressure during acute changes in carotid sinus transmural pressure.

New insights into differential baroreflex control of heart rate in humans

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Stromstad, M.; Wray, D. W.; Smith, S. A.; Raven, P. B.; Secher, N. H.

2003-01-01

Recent data indicate that bilateral carotid sinus denervation in patients results in a chronic impairment in the rapid reflex control of blood pressure during orthostasis. These findings are inconsistent with previous human experimental investigations indicating a minimal role for the carotid baroreceptor-cardiac reflex in blood pressure control. Therefore, we reexamined arterial baroreflex [carotid (CBR) and aortic baroreflex (ABR)] control of heart rate (HR) using newly developed methodologies. In 10 healthy men, 27 +/- 1 yr old, an abrupt decrease in mean arterial pressure (MAP) was induced nonpharmacologically by releasing a unilateral arterial thigh cuff (300 Torr) after 9 min of resting leg ischemia under two conditions: 1) ABR and CBR deactivation (control) and 2) ABR deactivation. Under control conditions, cuff release decreased MAP by 13 +/- 1 mmHg, whereas HR increased 11 +/- 2 beats/min. During ABR deactivation, neck suction was gradually applied to maintain carotid sinus transmural pressure during the initial 20 s after cuff release (suction). This attenuated the increase in HR (6 +/- 1 beats/min) and caused a greater decrease in MAP (18 +/- 2 mmHg, P < 0.05). Furthermore, estimated cardiac baroreflex responsiveness (DeltaHR/DeltaMAP) was significantly reduced during suction compared with control conditions. These findings suggest that the carotid baroreceptors contribute more importantly to the reflex control of HR than previously reported in healthy individuals.

Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats.

PubMed

Sévoz-Couche, Caroline; Brouillard, Charly; Camus, Françoise; Laude, Dominique; De Boer, Sietse F; Becker, Chrystel; Benoliel, Jean-Jacques

2013-04-01

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders.

Appropriate control time constant in relation to characteristics of the baroreflex vascular system in 1/R control of the total artificial heart.

PubMed

Mizuta, Sora; Saito, Itsuro; Isoyama, Takashi; Hara, Shintaro; Yurimoto, Terumi; Li, Xinyang; Murakami, Haruka; Ono, Toshiya; Mabuchi, Kunihiko; Abe, Yusuke

2017-09-01

1/R control is a physiological control method of the total artificial heart (TAH) with which long-term survival was obtained with animal experiments. However, 1/R control occasionally diverged in the undulation pump TAH (UPTAH) animal experiment. To improve the control stability of the 1/R control, appropriate control time constant in relation to characteristics of the baroreflex vascular system was investigated with frequency analysis and numerical simulation. In the frequency analysis, data of five goats in which the UPTAH was implanted were analyzed with first Fourier transform technique to examine the vasomotion frequency. The numerical simulation was carried out repeatedly changing baroreflex parameters and control time constant using the elements-expanded Windkessel model. Results of the frequency analysis showed that the 1/R control tended to diverge when very low frequency band that was an indication of the vasomotion frequency was relative high. In numerical simulation, divergence of the 1/R control could be reproduced and the boundary curves between the divergence and convergence of the 1/R control varied depending on the control time constant. These results suggested that the 1/R control tended to be unstable when the TAH recipient had high reflex speed in the baroreflex vascular system. Therefore, the control time constant should be adjusted appropriately with the individual vasomotion frequency.

Vascular Responsiveness in Adrenalectomized Rats with Corticosterone Replacement

NASA Technical Reports Server (NTRS)

Darlington, Daniel N.; Kaship, Kapil; Keil, Lanny C.; Dallman, Mary F.

1989-01-01

To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (-100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+O, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.

Enhanced vagal baroreflex response during 24 h after acute exercise

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Adams, W. C.

1991-01-01

We evaluated carotid-cardiac baroreflex responses in eight normotensive men (25-41 yr) on two different test days, each separated by at least 1 wk. On one day, baroreflex response was tested before and at 3, 6, 12, 18, and 24 h after graded supine cycle exercise to volitional exhaustion. On another day, this 24-h protocol was repeated with no exercise (control). Beat-to-beat R-R intervals were measured during external application of graded pressures to the carotid sinuses from 40 to -65 mmHg; changes of R-R intervals were plotted against carotid pressure (systolic pressure minus neck chamber pressure). The maximum slope of the response relationship increased (P less than 0.05) from preexercise to 12 h (3.7 +/- 0.4 to 7.1 +/- 0.7 ms/mmHg) and remained significantly elevated through 24 h. The range of the R-R response was also increased from 217 +/- 24 to 274 +/- 32 ms (P less than 0.05). No significant differences were observed during the control 24-h period. An acute bout of graded exercise designed to elicit exhaustion increases the sensitivity and range of the carotid-cardiac baroreflex response for 24 h and enhances its capacity to buffer against hypotension by increasing heart rate. These results may represent an underlying mechanism that contributes to blood pressure stability after intense exercise.

Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats

PubMed Central

Sévoz-Couche, Caroline; Brouillard, Charly; Camus, Françoise; Laude, Dominique; De Boer, Sietse F; Becker, Chrystel; Benoliel, Jean-Jacques

2013-01-01

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders. PMID:23297312

Effect of Voluntary Ethanol Consumption Combined with Testosterone Treatment on Cardiovascular Function in Rats: Influence of Exercise Training

PubMed Central

Engi, Sheila A.; Planeta, Cleopatra S.; Crestani, Carlos C.

2016-01-01

This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6), animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α1-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances. PMID:26760038

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

PubMed

Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

2016-09-01

Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

The degree of cardiac baroreflex involvement during active standing is associated with the quality of life in fibromyalgia patients.

PubMed

Zamunér, Antonio Roberto; Porta, Alberto; Andrade, Carolina Pieroni; Forti, Meire; Marchi, Andrea; Furlan, Raffaello; Barbic, Franca; Catai, Aparecida Maria; Silva, Ester

2017-01-01

Fibromyalgia syndrome (FMS) is a rheumatologic disorder characterized by chronic widespread pain, fatigue and other symptoms. Baroreflex dysfunction has been observed in women with FMS. However, it is unknown whether the limited involvement of the baroreflex control during an orthostatic stimulus has some impact on the quality of life of the FMS patient. Therefore, the aim of the study is evaluate the relationship between the quality of life of the FMS patient and indexes of the cardiovascular autonomic control as estimated from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP). We enrolled 35 women with FMS (age: 48.8±8.9 years; body mass index: 29.3±4.3 Kg/m2). The electrocardiogram, non-invasive finger blood pressure and respiratory activity were continuously recorded during 15 minutes at rest in supine position (REST) and in orthostatic position during active standing (STAND). Traditional cardiovascular autonomic control markers were assessed along with a Granger causality index assessing the strength of the causal relation from SAP to HP (CRSAP→HP) and measuring the degree of involvement of the cardiac baroreflex. The impact of FMS on quality of life was quantified by the fibromyalgia impact questionnaire (FIQ) and visual analog score for pain (VAS pain). No significant linear association was found between FIQ scores and the traditional cardiovascular indexes both at REST and during STAND (p>0.05). However, a negative relationship between CRSAP→HP during STAND and FIQ score was found (r = -0.56, p<0.01). Similar results were found with VAS pain. In conclusion, the lower the degree of cardiac baroreflex involvement during STAND in women with FMS, the higher the impact of FMS on the quality of life, thus suggesting that Granger causality analysis might be clinically helpful in assessing the state of the FMS patient.

The degree of cardiac baroreflex involvement during active standing is associated with the quality of life in fibromyalgia patients

PubMed Central

Porta, Alberto; Andrade, Carolina Pieroni; Forti, Meire; Marchi, Andrea; Furlan, Raffaello; Barbic, Franca; Catai, Aparecida Maria; Silva, Ester

2017-01-01

Fibromyalgia syndrome (FMS) is a rheumatologic disorder characterized by chronic widespread pain, fatigue and other symptoms. Baroreflex dysfunction has been observed in women with FMS. However, it is unknown whether the limited involvement of the baroreflex control during an orthostatic stimulus has some impact on the quality of life of the FMS patient. Therefore, the aim of the study is evaluate the relationship between the quality of life of the FMS patient and indexes of the cardiovascular autonomic control as estimated from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP). We enrolled 35 women with FMS (age: 48.8±8.9 years; body mass index: 29.3±4.3 Kg/m2). The electrocardiogram, non-invasive finger blood pressure and respiratory activity were continuously recorded during 15 minutes at rest in supine position (REST) and in orthostatic position during active standing (STAND). Traditional cardiovascular autonomic control markers were assessed along with a Granger causality index assessing the strength of the causal relation from SAP to HP (CRSAP→HP) and measuring the degree of involvement of the cardiac baroreflex. The impact of FMS on quality of life was quantified by the fibromyalgia impact questionnaire (FIQ) and visual analog score for pain (VAS pain). No significant linear association was found between FIQ scores and the traditional cardiovascular indexes both at REST and during STAND (p>0.05). However, a negative relationship between CRSAP→HP during STAND and FIQ score was found (r = -0.56, p<0.01). Similar results were found with VAS pain. In conclusion, the lower the degree of cardiac baroreflex involvement during STAND in women with FMS, the higher the impact of FMS on the quality of life, thus suggesting that Granger causality analysis might be clinically helpful in assessing the state of the FMS patient. PMID:28614420

Promethazine affects autonomic cardiovascular mechanisms minimally

NASA Technical Reports Server (NTRS)

Brown, T. E.; Eckberg, D. L.

1997-01-01

Promethazine hydrochloride, Phenergan, is a phenothiazine derivative with antihistaminic (H1), sedative, antiemetic, anticholinergic, and antimotion sickness properties. These properties have made promethazine a candidate for use in environments such as microgravity, which provoke emesis and motion sickness. Recently, we evaluated carotid baroreceptor-cardiac reflex responses during two Space Shuttle missions 18 to 20 hr after the 50 mg intramuscular administration of promethazine. Because the effects of promethazine on autonomic cardiovascular mechanisms in general and baroreflex function in particular were not known, we were unable to exclude a possible influence of promethazine on our results. Our purpose was to determine the ground-based effects of promethazine on autonomic cardiovascular control. Because of promethazine's antihistaminic and anticholinergic properties, we expected that a 50-mg intramuscular injection of promethazine would affect sympathetically and vagally mediated cardiovascular mechanisms. Eight healthy young subjects, five men and three women, were studied at rest in recumbency. All reported drowsiness as a result of the promethazine injection; most also reported nervous excitation, dry mouth, and fatigue. Three subjects had significant reactions: two reported excessive anxiety and one reported dizziness. Measurements were performed immediately prior to injection and 3.1 +/- 0.1 and 19.5 +/- 0.4 hr postinjection. We found no significant effect of promethazine on resting mean R-R interval, arterial pressure, R-R interval power spectra, carotid baroreflex function, and venous plasma catecholamine levels.

The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study.

PubMed

Gordin, Daniel; Fadl Elmula, Fadl Elmula M; Andersson, Bert; Gottsäter, Anders; Elf, Johan; Kahan, Thomas; Christensen, Kent Lodberg; Vikatmaa, Pirkka; Vikatmaa, Leena; Bastholm Olesen, Thomas; Groop, Per-Henrik; Olsen, Michael Hecht; Tikkanen, Ilkka

2017-10-01

To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of  ≥145 mm Hg, and/or a daytime diastolic ABPM of  ≥95 mm Hg after witnessed drug intake (including  ≥3 antihypertensive drugs, preferably including a diuretic). The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety. This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.

Heart rate variability in type 2 diabetes mellitus.

PubMed

Stuckey, Melanie I; Petrella, Robert J

2013-01-01

Heart rate variability (HRV) is a noninvasive measure of cardiac autonomic modulation. Time and frequency domain measures have primarily been examined in patients with type 2 diabetes mellitus (T2D). Not only do frequency domain HRV parameters tend to be reduced in T2D, but healthy individuals with low HRV are also more likely to develop T2D. Furthermore, patients with T2D with low HRV have an increased prevalence of complications and risk of mortality compared with those with normal autonomic function. These findings provide support for the use of HRV as a risk indicator in T2D. Exercise is considered an important component to T2D prevention and treatment strategies. To date, few studies have examined the changes in HRV with exercise in T2D. One study showed changes in resting HRV, two studies showed changes in HRV during or following acute stressors, and one study showed no changes in HRV but improvements in baroreflex sensitivity. The most pronounced changes in HRV were realized following the exercise intervention with the greatest frequency of supervised exercise sessions and with the greatest intensity and duration of exercise bouts. These findings suggest that exercise following current American College of Sports Medicine/American Diabetes Association guidelines may be important in the prevention and treatment of T2D to improve autonomic function and reduce the risk of complications and mortality.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence.

PubMed

Cruz, Fábio C; Duarte, Josiane O; Leão, Rodrigo M; Hummel, Luiz F V; Planeta, Cleopatra S; Crestani, Carlos C

2016-01-01

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc.

Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition

NASA Technical Reports Server (NTRS)

Bayorh, M. A.; Eatman, D.; Walton, M.; Socci, R. R.; Emmett, N.

2002-01-01

Cardiovascular deconditioning, sometimes manifested in astronauts during standing postflight, may be related to the impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-h post-suspension period in conscious male Sprague-Dawley rats to determine the role of prostacyclin in the observed post-suspension reduction in mean arterial pressure (MAP). The specific prostacyclin synthase inhibitor U-51605 (0.3 mg/kg), or saline, was administered intravenously prior to release from suspension and at 2 and 4 h post-suspension. During 7 days of suspension, MAP did not change, however, there was a post-suspension reduction in MAP which was associated with significant increases in plasma prostacyclin and nitric oxide. U-51605 attenuated the observed post-suspension hypotension and reduced plasma prostacyclin levels, but not nitric oxide levels. The baroreflex sensitivity for heart rate was modified by U-51605: increased MAP threshold and effective MAP range. Thus, the post-suspension reduction in mean arterial pressure may be due to overproduction of prostacyclin and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.

Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

PubMed

Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

2017-01-01

Background . Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods . The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results . Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

Orthostatic hypotension

NASA Technical Reports Server (NTRS)

Ninet, J.

1981-01-01

Basic orientation of the article, by the leader of a group of medical researchers associated with hospitals in Lyon, France, is toward definition and classification. A table divides OH (orthostatic hypotension) according to physiopathological classification into sympathicotonic and asympathicotonic types and then each of these into primary and secondary with subdivisions. The figure sketches organization and functioning of the baroreflex arc. Applications to clinical study of circulatory reflexes, listing measurement tests and the biological study of hormonal regulation listing the appropriate kinds of studies. Data are not given.

Modulation of baroreflex sensitivity by walnuts versus cashew nuts in subjects with metabolic syndrome.

PubMed

Schutte, Aletta E; Van Rooyen, Johannes M; Huisman, Hugo W; Mukuddem-Petersen, Janine; Oosthuizen, Welma; Hanekom, Susanna M; Jerling, Johann C

2006-06-01

Impaired baroreflex sensitivity (BRS) is associated with cardiovascular diseases and the metabolic syndrome. Because lipid abnormalities have been associated with impaired BRS, this study aimed to determine whether diets known to improve the lipid profile, namely a diet high in polyunsaturated fatty acids (walnuts) or monounsaturated fatty acids (cashew nuts), would improve BRS in subjects with metabolic syndrome (MS). A controlled feeding trial with a randomized, controlled, parallel study design was undertaken, which involved 62 subjects with MS. Subjects were stratified according to gender and age and were randomized into three groups receiving a control diet, or a diet high (20% energy) in walnuts or unsalted cashew nuts for 8 weeks while maintaining body weight. The BRS, C-reactive protein (CRP), and MS components were measured before and after the intervention. After the intervention, BRS in the walnut-fed study group decreased (P = .038) and that in the cashew-fed study group increased (P = .036), but the BRS in the control group did not change (P = .56). The percent change of the walnut versus cashew group differed (P = .019). Body mass index, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triacylglycerol did not change. The fasting glucose concentrations of the cashew group increased (P = .03). The significant improvements in BRS obtained by a diet rich in cashew nuts underline the beneficial cardiovascular effects of nuts. However, the opposite result was obtained with a diet rich in walnuts. These significant changes observed might indicate that BRS is particularly sensitive and influenced by changes in diet without changes in obesity.

Neuronal modelling of baroreflex response to orthostatic stress

NASA Astrophysics Data System (ADS)

Samin, Azfar

The accelerations experienced in aerial combat can cause pilot loss of consciousness (GLOC) due to a critical reduction in cerebral blood circulation. The development of smart protective equipment requires understanding of how the brain processes blood pressure (BP) information in response to acceleration. We present a biologically plausible model of the Baroreflex to investigate the neural correlates of short-term BP control under acceleration or orthostatic stress. The neuronal network model, which employs an integrate-and-fire representation of a biological neuron, comprises the sensory, motor, and the central neural processing areas that form the Baroreflex. Our modelling strategy is to test hypotheses relating to the encoding mechanisms of multiple sensory inputs to the nucleus tractus solitarius (NTS), the site of central neural processing. The goal is to run simulations and reproduce model responses that are consistent with the variety of available experimental data. Model construction and connectivity are inspired by the available anatomical and neurophysiological evidence that points to a barotopic organization in the NTS, and the presence of frequency-dependent synaptic depression, which provides a mechanism for generating non-linear local responses in NTS neurons that result in quantifiable dynamic global baroreflex responses. The entire physiological range of BP and rate of change of BP variables is encoded in a palisade of NTS neurons in that the spike responses approximate Gaussian 'tuning' curves. An adapting weighted-average decoding scheme computes the motor responses and a compensatory signal regulates the heart rate (HR). Model simulations suggest that: (1) the NTS neurons can encode the hydrostatic pressure difference between two vertically separated sensory receptor regions at +Gz, and use changes in that difference for the regulation of HR; (2) even though NTS neurons do not fire with a cardiac rhythm seen in the afferents, pulse-rhythmic activity is regained downstream provided the input phase information in preserved centrally; (3) frequency-dependent synaptic depression, which causes temporal variations in synaptic strength due to changes in input frequency, is a possible mechanism of non-linear dynamic baroreflex gain control. Synaptic depression enables the NTS neuron to encode dBP/dt but to lose information about the steady state firing of the afferents.

Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure

PubMed Central

Verma, Ajay K.; Xu, Da; Garg, Amanmeet; Cote, Anita T.; Goswami, Nandu; Blaber, Andrew P.; Tavakolian, Kouhyar

2017-01-01

Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to −40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR↔SBP and RR↔MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR→SBP and RR→MAP) showed a significantly (p < 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP→RR and MAP→RR). In response to moderate category hemorrhage (−30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR→SBP (p = 0.76), RR→MAP (p = 0.60), and SBP→RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP→RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP→RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression. PMID:29114227

Baroreflex sensitivity in acute hypoxia and carbohydrate loading.

PubMed

Klemenc, Matjaž; Golja, Petra

2011-10-01

Hypoxia decreases baroreflex sensitivity (BRS) and can be a sufficient cause for syncope in healthy individuals. Carbohydrate loading enhances efferent sympathetic activity, which affects cardiac contractility, heart rate and vascular resistance, the main determinants of blood pressure. Thus, in both normoxia and hypoxia, carbohydrate loading may be more than simply metabolically beneficial, as it may affect blood pressure regulation. We hypothesised that carbohydrate loading will, in both normoxia and hypoxia, alter the regulation of blood pressure, as reflected in a change in baroreflex sensitivity. Fourteen subjects participated in two experiments, composed of a 15-min normoxic period, after which the subjects ingested water or an equal amount of water with carbohydrates. A 30-min rest period was then followed by a 10-min second normoxic and a 30-min hypoxic period. Blood pressure and heart rate were monitored continuously during the experiment to determine BRS. Despite an increased sympathetic activation, reflected in increased heart rate (P < 0.001) BRS was lower (P < 0.01) after carbohydrate loading, as compared to the water experiment, in both normoxic [23.7 (12.4) versus 28.8 (13.8) ms/mmHg] and hypoxic [16.8 (11.0) versus 24.3 (12.3) ms/mmHg] phases of the present study. As BRS was decreased in acute hypoxic exposure, the results confirm that hypoxia interferes with blood pressure regulation. However, although oral carbohydrate loading induced sympathoexcitation, it did not improve blood pressure regulation in hypoxia, as evident from the BRS data. Baroreflex effects of other forms of carbohydrate loading, not causing postprandial blood shifts to digestive system, should therefore be investigated.

Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans

PubMed Central

Limberg, Jacqueline K; Taylor, Jennifer L; Dube, Simmi; Basu, Rita; Basu, Ananda; Joyner, Michael J; Wehrwein, Erica A

2014-01-01

Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor mediated responses. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia) and hypothesized: 1) activation of the carotid body chemoreceptors with hypoglycaemia would reduce spontaneous cardiac baroreflex sensitivity (sCBRS) in healthy humans and, 2) desensitization of the carotid chemoreceptors with hyperoxia would restore sCBRS to baseline levels during hypoglycaemia. Ten young healthy adults completed two 180-min hyperinsulinaemic (2 mU.kg FFM−1.min−1), hypoglycaemic (~3.2 µmol.mL−1) clamps, separated by at least one week and randomized to normoxia (PaO2 122±10 mmHg) or hyperoxia (PaO2 424±123 mmHg; to blunt activation of the carotid body glomus cells). Changes in heart rate, blood pressure, plasma catecholamines, heart rate variability (HRV), and sCBRS were assessed. During hypoglycaemia, HRV and sCBRS were reduced (p<0.05) and the baroreflex working range was shifted to higher heart rates. When hyperoxia was superimposed on hypoglycaemia, there was a greater reduction in blood pressure and a blunted rise in heart rate when compared to normoxic conditions (p<0.05); however, there was no detectable effect of hyperoxia on sCBRS or HRV during hypoglycaemia (p>0.05). In summary, hypoglycaemia-mediated changes in HRV and sCBRS cannot be exclusively attributed to the carotid chemoreceptors; however, the chemoreceptors appear to play a role in resetting the baroreflex working range during hypoglycaemia. PMID:24414173

Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

NASA Technical Reports Server (NTRS)

Cox, James F.; Tahvanainen, Kari U O.; Kuusela, Tom A.; Levine, Benjamin D.; Cooke, William H.; Mano, Tadaaki; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Ertl, Andrew C.;

Influence of Microgravity on Arterial Baroreflex Responses Triggered by Valsalva's Maneuver

NASA Technical Reports Server (NTRS)

Eckberg, Dwain L.; Cox, James F.; Tahvanainen, Kari U. O.; Kuusela, Tom A.; Cooke, William H.; Ames, Jimey E.

2003-01-01

When astronauts return to Earth and stand upright, their heart rates may speed inordinately, their blood pressures may fall, and some returning astronauts may even faint. Since physiological adjustments to standing are mediated importantly by pressure-regulating reflexes (baroreflexes), we studied involuntary (or autonomic) nerve and blood pressure responses of astronauts to four, 15-second periods of 15- and 30-mmHg straining (Valsalva'. maneuver). We measured the electrocardiogram, finger blood pressure, respiration, and muscle sympathetic nerve activity in four healthy male astronauts before and during the 16-day Neurolab Space Shuttle mission. We found that although microgravity provoked major autonomic changes, no astronaut experienced fainting symptoms after the mission. Blood pressure fell more during straining in space than on Earth (the average reduction of systolic pressure with 30-mmHg straining was 49 mmHg during and 27 mmHg before the mission). However, the increases of muscle sympathetic nerve activity that were triggered by straining were also larger in space than on Earth. As a result, the gain of the sympathetic baroreflex, taken as the total sympathetic nerve response divided by the maximum pressure reduction during straining, was the same in space as on Earth. In contrast, heart rate changes, which are mediated by changes of vagus nerve activity, were smaller in space. This and earlier research suggest that exposure to microgravity augments blood pressure and sympathetic adjustments to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex responsiveness. The changes that we documented can be explained economically as a consequence of the blood volume reduction that occurs in space.

Recurrent syncope, orthostatic hypotension and volatile hypertension: think outside the box.

PubMed

Aung, Thein; Fan, Wuqiang; Krishnamurthy, Mahesh

2013-01-01

The baroreceptors in the neck and aortic arch are important regulators of sudden blood pressure changes. They are innervated by CN IX and X and synapse in the brainstem. Baroreceptor failure is an under-recognized cause of recurrent syncope, orthostatic hypotension, and volatile hypertension, which is refractory to and may in fact worsen with conventional treatments. Baroreflex failure can be the result of neck and chest radiation, head and neck surgery, and cerebrovascular accidents involving the brainstem nuclei. The management of baroreflex failure is a challenge since patient education, lifestyle changes, and family support are extremely important in managing blood pressure. Leg exercises and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating orthostatic hypotension. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest. Temporal relationship between symptoms onset and the history of head, neck, and upper chest radiation or trauma is important in reaching a diagnosis.

Analysis of pressure head-flow loops of pulsatile rotodynamic blood pumps.

PubMed

Jahren, Silje E; Ochsner, Gregor; Shu, Fangjun; Amacher, Raffael; Antaki, James F; Vandenberghe, Stijn

2014-04-01

The clinical importance of pulsatility is a recurring topic of debate in mechanical circulatory support. Lack of pulsatility has been identified as a possible factor responsible for adverse events and has also demonstrated a role in myocardial perfusion and cardiac recovery. A commonly used method for restoring pulsatility with rotodynamic blood pumps (RBPs) is to modulate the speed profile, synchronized to the cardiac cycle. This introduces additional parameters that influence the (un)loading of the heart, including the timing (phase shift) between the native cardiac cycle and the pump pulses, and the amplitude of speed modulation. In this study, the impact of these parameters upon the heart-RBP interaction was examined in terms of the pressure head-flow (HQ) diagram. The measurements were conducted using a rotodynamic Deltastream DP2 pump in a validated hybrid mock circulation with baroreflex function. The pump was operated with a sinusoidal speed profile, synchronized to the native cardiac cycle. The simulated ventriculo-aortic cannulation showed that the level of (un)loading and the shape of the HQ loops strongly depend on the phase shift. The HQ loops displayed characteristic shapes depending on the phase shift. Increased contribution of native contraction (increased ventricular stroke work [WS ]) resulted in a broadening of the loops. It was found that the previously described linear relationship between WS and the area of the HQ loop for constant pump speeds becomes a family of linear relationships, whose slope depends on the phase shift. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

Sympathetic nerve traffic and baroreflex function in optimal, normal, and high-normal blood pressure states.

PubMed

Seravalle, Gino; Lonati, Laura; Buzzi, Silvia; Cairo, Matteo; Quarti Trevano, Fosca; Dell'Oro, Raffaella; Facchetti, Rita; Mancia, Giuseppe; Grassi, Guido

2015-07-01

Adrenergic activation and baroreflex dysfunction are common in established essential hypertension, elderly hypertension, masked and white-coat hypertension, resistant hypertension, and obesity-related hypertension. Whether this autonomic behavior is peculiar to established hypertension or is also detectable in the earlier clinical phases of the disease, that is, the high-normal blood pressure (BP) state, is still largely undefined, however. In 24 individuals with optimal BP (age: 37.1  ±  2.1 years, mean  ±  SEM) and in 27 with normal BP and 38 with high-normal BP, age matched with optimal BP, we measured clinic, 24-h and beat-to-beat BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) at rest and during baroreceptor stimulation and deactivation. Measurements also included anthropometric as well as echocardiographic and homeostasis model assessment (HOMA) index. For similar anthropometric values, clinic, 24-h ambulatory, and beat-to-beat BPs were significantly greater in normal BP than in optimal BP. This was the case when the high-normal BP group was compared to the normal and optimal BP groups. MSNA (but not HR) was also significantly greater in high-normal BP than in normal BP and optimal BP (51.3  ±  2.0 vs. 40.3  ±  2.3 and 41.1 ± 2.6  bursts per 100  heartbeats, respectively, P < 0.01). The sympathetic activation seen in high-normal BP was coupled with an impairment of baroreflex HR control (but not MSNA) and with a significant increase in HOMA Index, which showed a significant direct relationship with MSNA. Thus, independently of which BP the diagnosis is based, high-normal BP is a condition characterized by a sympathetic activation. This neurogenic alteration, which is likely to be triggered by metabolic rather than reflex alterations, might be involved, together with other factors, in the progression of the condition to established hypertension.

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

PubMed Central

Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

2013-01-01

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients. PMID:24060993

Carotid Baroreflex Function During Prolonged Exercise

NASA Technical Reports Server (NTRS)

Raven, P. B.

1999-01-01

Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative pressure (-10 torr) to mimic spaceflight- related decreases in cardiac filling volumes.

Pyridostigmine Improves the Effects of Resistance Exercise Training after Myocardial Infarction in Rats

PubMed Central

Feriani, Daniele J.; Coelho-Júnior, Hélio J.; de Oliveira, Juliana C. M. F.; Delbin, Maria A.; Mostarda, Cristiano T.; Dourado, Paulo M. M.; Caperuto, Érico C.; Irigoyen, Maria C. C.; Rodrigues, Bruno

2018-01-01

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Exercise training and pharmacological treatments are important strategies to minimize the deleterious effects of MI. However, little is known about the effects of resistance training combined with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on the inflammatory profile after MI. Thus, in the present study, male Wistar rats were randomly assigned into: control (Cont); sedentary infarcted (Inf); PYR – treated sedentary infarcted rats (Inf+P); infarcted rats undergoing resistance exercise training (Inf+RT); and infarcted rats undergoing PYR treatment plus resistance training (Inf+RT+P). After 12 weeks of resistance training (15–20 climbs per session, with a 1-min rest between each climb, at a low to moderate intensity, 5 days a week) and/or PYR treatment (0.14 mg/mL of drink water), hemodynamic function, autonomic modulation, and cytokine expressions were evaluated. We observed that 3 months of PYR treatment, either alone or in combination with exercise, can improve the deleterious effects of MI on left ventricle dimensions and function, baroreflex sensitivity, and autonomic parameters, as well as systemic and tissue inflammatory profile. Furthermore, additional benefits in a maximal load test and anti-inflammatory state of skeletal muscle were found when resistance training was combined with PYR treatment. Thus, our findings suggest that the combination of resistance training and PYR may be a good therapeutic strategy since they promote additional benefits on skeletal muscle anti-inflammatory profile after MI. PMID:29483876

The autonomic laboratory

NASA Technical Reports Server (NTRS)

Low, P. A.; Opfer-Gehrking, T. L.

1999-01-01

The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

Respiratory modulation of human autonomic rhythms

NASA Technical Reports Server (NTRS)

Badra, L. J.; Cooke, W. H.; Hoag, J. B.; Crossman, A. A.; Kuusela, T. A.; Tahvanainen, K. U.; Eckberg, D. L.

2001-01-01

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

IABP timing and ventricular performance--comparison between a compliant and a stiffer aorta: a hybrid model study including baroreflex.

PubMed

Fresiello, Libera; Khir, Ashraf W; Di Molfetta, Arianna; Kozarski, Maciej; Ferrari, Gianfranco

2013-11-01

The aim of this study was to investigate the effects of the intra aortic balloon pump (IABP) and of aortic compliance on left ventricular performance, including the effects of baroreflex control.
 The study was conducted using a hybrid cardiovascular simulator, including a computational cardiovascular sub-model, a hydraulic sub-model of the descending aorta, and a baroreflex computational sub-model. A 40 cc balloon was inserted into a rubber tube component of the hydraulic sub-model. A comparative analysis was conducted for two aortic compliances (C1 = 2.4 and C2 = 1.43 cm3/mmHg, corresponding to an aortic pulse pressure of 23 mmHg and 35 mmHg, respectively), driving the balloon for different trigger timings.
 Under C1 conditions, the IABP induced higher effects on baroreflex activity (decrement of sympathetic efferent activity: 10% for C1 and 14.7% for C2) and ventricular performance (increment of cardiac output (CO): 3.7% for C1 and 5.2% for C2, increment of endocardial viability ratio (EVR): 24.8% for C1 and 55% for C2). The best balloon timing was different for C1 and C2: inflation trigger timing (from the dicrotic notch) -0.09 s for C1 and -0.04 s for C2, inflation duration 0.25 s for C1 and 0.2 s for C2.
 Early inflation ensures better EVR, CO, and an increment of the afferent nerve activity, hence causing peripheral resistance and heart rate to decrease. The best balloon timing depends on aortic compliance, thus suggesting the need for a therapy tailored to the specific conditions of individual patients.

Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

NASA Astrophysics Data System (ADS)

Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

2017-02-01

Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

Effect of exercise training on cardiopulmonary baroreflex control of forearm vascular resistance in humans

NASA Technical Reports Server (NTRS)

Mack, G. W.; Convertino, V. A.; Nadel, E. R.

1993-01-01

We studied the stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR) in four groups of male volunteer subjects: i) unfit, ii) physically fit, iii) before and after 10 wk of endurance training (chronic blood volume expansion), and iv) before and after acute blood volume expansion. We assessed the relationship between reflex stimulus, i.e., changes in central venous pressure and response, i.e., FVR, during unloading of cardiopulmonary mechanoreceptors with lower body negative pressure (LBNP, 0 to -20 mm Hg). The slope of the linear relationship between FVR and CVP, the index of the responsiveness of this baroreflex, was significantly diminished (> 50%) in the fit subjects compared with the unfit. The slope of the FVR-CVP relationship was inversely correlated with the subject's total blood volume, suggesting that blood volume expansion was related to the attenuated CP baroreflex. In the exercise training study, maximal oxygen consumption and blood volume increased following 10 wk of endurance training (N = 14) but were unchanged in the time control group (N = 7). The slope of the FVR-CVP relationship was significantly reduced (32%) following 10 wk of training but was unchanged in the time control group. The reduction in slope of the FVR-CVP relationship was inversely related to the increase in blood volume associated with exercise training. Acute blood volume expansion 8 ml.kg-1 body weight with 5% human serum albumin solution) significantly reduced the slope of the FVR-CVP relationship. These data support the hypothesis that the attenuated forearm vascular reflex in physically fit individuals is related to a training-induced hypervolemia.(ABSTRACT TRUNCATED AT 250 WORDS).

Interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans

NASA Technical Reports Server (NTRS)

Ray, C. A.

2000-01-01

Muscle sympathetic nerve activity (MSNA) is altered by vestibular otolith stimulation. This study examined interactive effects of the vestibular system and baroreflexes on MSNA in humans. In study 1, MSNA was measured during 4 min of lower body negative pressure (LBNP) at either -10 or -30 mmHg with subjects in prone posture. During the 3rd min of LBNP, subjects lowered their head over the end of a table (head-down rotation, HDR) to engage the otolith organs. The head was returned to baseline upright position during the 4th min. LBNP increased MSNA above baseline during both trials with greater increases during the -30-mmHg trial. HDR increased MSNA further during the 3rd min of LBNP at -10 and -30 mmHg (Delta32% and Delta34%, respectively; P < 0.01). MSNA returned to pre-HDR levels during the 4th min of LBNP when the head was returned upright. In study 2, MSNA was measured during HDR, LBNP, and simultaneously performed HDR and LBNP. The sum of MSNA responses during individual HDR and LBNP trials was not significantly different from that observed during HDR and LBNP performed together (Delta131 +/- 28 vs. Delta118 +/- 47 units and Delta340 +/- 77 vs. Delta380 +/- 90 units for the -10 and -30 trials, respectively). These results demonstrate that vestibular otolith stimulation can increase MSNA during unloading of the cardiopulmonary and arterial baroreflexes. Also, the interaction between the vestibulosympathetic reflex and baroreflexes is additive in humans. These studies indicate that the vestibulosympathetic reflex may help defend against orthostatic challenges in humans by increasing sympathetic outflow.

Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-08-01

To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus and aortic depressor nerve stimulation, respectively.

Effects of intra-aortic balloon pump timing on baroreflex activities in a closed-loop cardiovascular hybrid model.

PubMed

Fresiello, Libera; Khir, Ashraf William; Di Molfetta, Arianna; Kozarski, Maciej; Ferrari, Gianfranco

2013-03-01

Despite 50 years of research to assess the intra-aortic balloon pump (IABP) effects on patients' hemodynamics, some issues related to the effects of this therapy are still not fully understood. One of these issues is the effect of IABP, its inflation timing and duration on peripheral circulation autonomic controls. This work provides a systematic analysis of IABP effects on baroreflex using a cardiovascular hybrid model, which consists of computational and hydraulic submodels. The work also included a baroreflex computational model that was connected to a hydraulic model with a 40-cm(3) balloon. The IABP was operated at different inflation trigger timings (-0.14 to 0.31 s) and inflation durations (0.05-0.45 s), with time of the dicrotic notch being taken as t = 0. Baroreflex-dependent parameters-afferent and efferent pathway activity, heart rate, peripheral resistance, and venous tone-were evaluated at each of the inflation trigger times and durations considered. Balloon early inflation (0.09 s before the dicrotic notch) with inflation duration of 0.25 s generated a maximum net increment of afferent pathway activity of 10%, thus leading to a decrement of efferent sympathetic activity by 15.3% compared with baseline values. These times also resulted in a reduction in peripheral resistance and heart rate by 4 and 4.3% compared with baseline value. We conclude that optimum IABP triggering time results in positive effects on peripheral circulation autonomic controls. Conversely, if the balloon is not properly timed, peripheral resistance and heart rate may even increase, which could lead to detrimental outcomes. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Eatman, D.; Walton, M.; Socci, R. R.; Emmett, N.; Bayorh, M. A.

2003-01-01

The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.

NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex.

PubMed

Makeham, John M; Goodchild, Ann K; Pilowsky, Paul M

2005-06-01

The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5-11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O(2))11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O(2))11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.

Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

PubMed Central

Quagliotto, E.; Casali, K.R.; Dal Lago, P.; Rasia-Filho, A.A.

2014-01-01

The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP50, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV. PMID:25424367

Hypertension Does Not Alter the Increase in Cardiac Baroreflex Sensitivity Caused by Moderate Cold Exposure

PubMed Central

Hintsala, Heidi E.; Kiviniemi, Antti M.; Tulppo, Mikko P.; Helakari, Heta; Rintamäki, Hannu; Mäntysaari, Matti; Herzig, Karl-Heinz; Keinänen-Kiukaanniemi, Sirkka; Jaakkola, Jouni J. K.; Ikäheimo, Tiina M.

2016-01-01

Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55–65 years) who underwent a whole-body cold exposure (−10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04–0.15 Hz) and high frequency (0.15–0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg2, compared with hypertensive group [0 (−13, 20) mmHg2]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension. PMID:27313543

Commissural NTS lesions enhance the pressor response to central cholinergic and adrenergic activation.

PubMed

Vieira, Alexandre A; De Luca, Laurival A; Colombari, Eduardo; Colombari, Debora S A; Menani, José V

2012-07-11

Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) in rats enhance the pressor response to bilateral carotid occlusion or to intravenous infusion of hypertonic NaCl without changing baroreflex responses. In an opposite direction, commNTS lesions abolish the pressor responses to peripheral chemoreflex activation. These opposite effects of commNTS lesions apparently result from an impairment of sympathetic activation in one case and in a facilitation of vasopressin secretion in the others. In the present study, we investigated the effects of the electrolytic lesions of the commNTS in the pressor responses that depend on sympathetic activation and vasopressin secretion produced by central cholinergic or adrenergic activation with intracerebroventricular (i.c.v.) injections of carbachol or noradrenaline, respectively, in unanesthetized rats. Male Holtzman rats (280-320 g, n=8-15/group) with acute (1 day) or chronic (21 days) sham or commNTS lesions (1 mA×10 s) and a stainless steel cannula implanted in the lateral ventricle were used. Acute commNTS lesions increased the pressor response to i.c.v. injection of carbachol (0.5 nmol/1μ1) (52 ± 2, vs. sham: 37 ± 2mm Hg) or noradrenaline (80 nmol/1μl) (45 ± 6, vs. sham: 30 ± 3 mm Hg), whereas chronic commNTS lesions did not affect the pressor responses to the same treatments. Lesions of the commNTS impaired chemoreflex responses produced by intravenous KCN, without changing baroreflex responses. The results suggest that commNTS-dependent inhibitory signals are involved in the modulation of the pressor responses to central cholinergic and adrenergic activation, probably limiting vasopressin secretion. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Visual- and Vestibular-Autonomic Influence on Short-Term Cardiovascular Regulatory Mechanisms

NASA Technical Reports Server (NTRS)

Mullen, Thomas J.; Ramsdell, Craig D.

1999-01-01

This synergy project was a one-year effort conducted cooperatively by members of the NSBRI Cardiovascular Alterations and Neurovestibular Adaptation Teams in collaboration with NASA Johnson Space Center (JSC) colleagues. The objective of this study was to evaluate visual autonomic interactions on short-term cardiovascular regulatory mechanisms. Based on established visual-vestibular and vestibular-autonomic shared neural pathways, we hypothesized that visually induced changes in orientation will trigger autonomic cardiovascular reflexes. A second objective was to compare baroreflex changes during postural changes as measured with the new Cardiovascular System Identification (CSI) technique with those measured using a neck barocuff. While the neck barocuff stimulates only the carotid baroreceptors, CSI provides a measure of overall baroreflex responsiveness. This study involved a repeated measures design with 16 healthy human subjects (8 M, 8 F) to examine cardiovascular regulatory responses during actual and virtual head-upright tilts. Baroreflex sensitivity was first evaluated with subjects in supine and upright positions during actual tilt-table testing using both neck barocuff and CSI methods. The responses to actual tilts during this first session were then compared to responses during visually induced tilt and/or rotation obtained during a second session.

Altered Nocturnal Cardiovascular Control in Children With Sleep-Disordered Breathing.

PubMed

El-Hamad, Fatima; Immanuel, Sarah; Liu, Xiao; Pamula, Yvonne; Kontos, Anna; Martin, James; Kennedy, Declan; Kohler, Mark; Porta, Alberto; Baumert, Mathias

2017-10-01

To assess cardiovascular control during sleep in children with sleep-disordered breathing (SDB) and the effect of adenotonsillectomy in comparison to healthy nonsnoring children. Cardiorespiratory signals obtained from overnight polysomnographic recordings of 28 children with SDB and 34 healthy nonsnoring children were analyzed. We employed an autoregressive closed-loop model with heart period (RR) and pulse transit time (PTT) as outputs and respiration as an external input to obtain estimates of respiratory gain and baroreflex gain. Mean and variability of PTT were increased in children with SDB across all stages of sleep. Low frequency power of RR and PTT were attenuated during non-rapid eye movement (REM) sleep. Baroreflex sensitivity was reduced in children with SDB in stage 2 sleep, while respiratory gain was increased in slow wave sleep. After adenotonsillectomy, these indices normalized in the SDB group attaining values comparable to those of healthy children. In children with mild-to-moderate SDB, vasomotor activity is increased and baroreflex sensitivity decreased during quiet, event-free non-REM sleep. Adenotonsillectomy appears to reverse this effect. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

STS-40 crew trains in JSC's SLS mockup located in Bldg 36

NASA Image and Video Library

1987-03-10

STS-40 Payload Specialist Millie Hughes-Fulford along with backup payload specialist Robert Ward Phillips familiarize themselves with Spacelab Life Sciences 1 (SLS-1) equipment. The two scientists are in JSC's Life Sciences Project Division (LSPD) SLS mockup located in the Bioengineering and Test Support Facility Bldg 36. Hughes-Fulford, in the center aisle, pulls equipment from an overhead stowage locker while Phillips, in the foreground, experiments with the baroreflex neck pressure chamber at Rack 11. The baroreflex collar will be used in conjuction with Experiment No. 022, Influence of Weightlessness Upon Human Autonomic Cardiovascular Control. Behind Phillips in the center aisle are body mass measurement device (BMMD) (foreground) and the stowed bicycle ergometer.

Cardiorespiratory interactions to external stimuli.

PubMed

Bernardi, L; Porta, C; Spicuzza, L; Sleight, P

2005-09-01

Respiration is a powerful modulator of heart rate variability, and of baro- or chemo-reflex sensitivity. This occurs via a mechanical effect of breathing that synchronizes all cardiovascular variables at the respiratory rhythm, particularly when this occurs at a particular slow rate coincident with the Mayer waves in arterial pressure (approximately 6 cycles/min). Recitation of the rosary prayer (or of most mantras), induces a marked enhancement of these slow rhythms, whereas random verbalization or random breathing does not. This phenomenon in turn increases baroreflex sensitivity and reduces chemoreflex sensitivity, leading to increases in parasympathetic and reductions in sympathetic activity. The opposite can be seen during either verbalization or mental stress tests. Qualitatively similar effects can be obtained even by passive listening to more or less rhythmic auditory stimuli, such as music, and the speed of the rhythm (rather than the style) appears to be one of the main determinants of the cardiovascular and respiratory responses. These findings have clinical relevance. Appropriate modulation of breathing, can improve/restore autonomic control of cardiovascular and respiratory systems in relevant diseases such as hypertension and heart failure, and might therefore help improving exercise tolerance, quality of life, and ultimately, survival.

Impaired baroreflex sensitivity, carotid stiffness, and exaggerated exercise blood pressure: a community-based analysis from the Paris Prospective Study III.

PubMed

Sharman, James E; Boutouyrie, Pierre; Perier, Marie-Cécile; Thomas, Frédérique; Guibout, Catherine; Khettab, Hakim; Pannier, Bruno; Laurent, Stéphane; Jouven, Xavier; Empana, Jean-Philippe

2018-02-14

People with exaggerated exercise blood pressure (BP) have adverse cardiovascular outcomes. Mechanisms are unknown but could be explained through impaired neural baroreflex sensitivity (BRS) and/or large artery stiffness. This study aimed to determine the associations of carotid BRS and carotid stiffness with exaggerated exercise BP. Blood pressure was recorded at rest and following an exercise step-test among 8976 adults aged 50 to 75 years from the Paris Prospective Study III. Resting carotid BRS (low frequency gain, from carotid distension rate, and heart rate) and stiffness were measured by high-precision echotracking. A systolic BP threshold of ≥ 150 mmHg defined exaggerated exercise BP and ≥140/90 mmHg defined resting hypertension (±antihypertensive treatment). Participants with exaggerated exercise BP had significantly lower BRS [median (Q1; Q3) 0.10 (0.06; 0.16) vs. 0.12 (0.08; 0.19) (ms2/mm) 2×108; P < 0.001] but higher stiffness [mean ± standard deviation (SD); 7.34 ± 1.37 vs. 6.76 ± 1.25 m/s; P < 0.001) compared to those with non-exaggerated exercise BP. However, only lower BRS (per 1SD decrement) was associated with exaggerated exercise BP among people without hypertension at rest {specifically among those with optimal BP; odds ratio (OR) 1.16 [95% confidence intervals (95% CI) 1.01; 1.33], P = 0.04 and high-normal BP; OR, 1.19 (95% CI 1.07; 1.32), P = 0.001} after adjustment for age, sex, body mass index, smoking, alcohol, total cholesterol, high-density lipoprotein cholesterol, resting heart rate, and antihypertensive medications. Impaired BRS, but not carotid stiffness, is independently associated with exaggerated exercise BP even among those with well controlled resting BP. This indicates a potential pathway from depressed neural baroreflex function to abnormal exercise BP and clinical outcomes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Antihypertensive effect of Carica papaya via a reduction in ACE activity and improved baroreflex.

PubMed

Brasil, Girlandia Alexandre; Ronchi, Silas Nascimento; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Romão, Wanderson; da Costa, Helber Barcellos; Scherer, Rodrigo; Ventura, José Aires; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

2014-11-01

The aims of this study were to evaluate the antihypertensive effects of the standardised methanolic extract of Carica papaya, its angiotensin converting enzyme inhibitory effects in vivo, its effect on the baroreflex and serum angiotensin converting enzyme activity, and its chemical composition. The chemical composition of the methanolic extract of C. papaya was evaluated by liquid chromatography-mass/mass and mass/mass spectrometry. The angiotensin converting enzyme inhibitory effect was evaluated in vivo by Ang I administration. The antihypertensive assay was performed in spontaneously hypertensive rats and Wistar rats that were treated with enalapril (10 mg/kg), the methanolic extract of C. papaya (100 mg/kg; twice a day), or vehicle for 30 days. The baroreflex was evaluated through the use of sodium nitroprusside and phenylephrine. Angiotensin converting enzyme activity was measured by ELISA, and cardiac hypertrophy was evaluated by morphometric analysis. The methanolic extract of C. papaya was standardised in ferulic acid (203.41 ± 0.02 µg/g), caffeic acid (172.60 ± 0.02 µg/g), gallic acid (145.70 ± 0.02 µg/g), and quercetin (47.11 ± 0.03 µg/g). The flavonoids quercetin, rutin, nicotiflorin, clitorin, and manghaslin were identified in a fraction of the extract. The methanolic extract of C. papaya elicited angiotensin converting enzyme inhibitory activity. The antihypertensive effects elicited by the methanolic extract of C. papaya were similar to those of enalapril, and the baroreflex sensitivity was normalised in treated spontaneously hypertensive rats. Plasma angiotensin converting enzyme activity and cardiac hypertrophy were also reduced to levels comparable to the enalapril-treated group. These results may be associated with the chemical composition of the methanolic extract of C. papaya, and are the first step into the development of a new phytotherapic product which could be used in the treatment of hypertension. Georg Thieme Verlag KG Stuttgart · New York.

Diminished Baroreflex Control of Forearm Vascular Resistance Following Training

NASA Technical Reports Server (NTRS)

Mack, G. W.; Thompson, C. A.; Doerr, D. F.; Nadel, E. R.; Convertino, V. A.

1991-01-01

The stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR units in mm Hg x min x I00 ml/ml) were studied in 14 volunteers before and after 10 wk of endurance training. We assessed the relationship betaleen reflex stimulus (changes in central venous pressure, CVP) and response (FVR) during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP, 0 to - 2O mm Hg). Changes in CVP during LBNP were estimated from pressure changes in a large peripheral vein in the dependent arm of the subject in the right lateral decubitus position. Maximal oxygen uptake (VO(sub 2max)) and total blood volume increased with endurance training from 37.8 +/- 1.4 ml/min x kg and 63.6 +/- 2.1 ml/kg to 45.3 +/- 1.4 ml/ min x kg and 69.3 +/- 2.8 ml/kg respectively (P less than 0.05). Reflex forearm vasoconstriction occurred in response to a reduction in estimated CVP, and the absolute change in FVR per unit of CVP was reduced from -5.96 +/- 0.79 to -4.06 +/- 0.52 units x mm/ Hg (P less than 0.05) following exercise training but was unchanged from -6.10 to 0.57 to -6.22 +/- 0.94 units x mm/ Hg for the time control group (N = 7). Resting values for FVR were similar before and after exercise training; however, resting estimated CVP was elevated from 9.5 +/- 0.5 mm x Hg before training to 11.3 +/- 0.6 mm x Hg after training. The reduction in sensitivity of the cardiopulmonary baroreflex control of FVR was linearly related to the increase in blood volume (r = 0.65, P less than 0.05). suggesting that diminished cardiopulmonary baroreflex control of FVR in physically fit individuals is related, in part, to a training-induced blood volume expansion.

Arterial baroreflex control of muscle blood flow at the onset of voluntary locomotion in mice

PubMed Central

Masuki, Shizue; Nose, Hiroshi

2003-01-01

To assess the role of arterial baroreflex control in muscle blood flow (MBF) and voluntary locomotion, mean arterial pressure (MAP), MBF, and electromyograms (EMGs) were measured in freely moving mice before (CNT) and after blocking the afferent or efferent pathway of arterial baroreflexes, carotid sinus denervation (CSD), or intraperitoneal administration of phentolamine (BLK), respectively. MAP was measured through a catheter placed in the femoral artery. MBF was measured with a needle-type laser-Doppler flowmeter and recorded through a low-pass filter with an edge frequency of 0.1 Hz. The frequency and duration of locomotion were judged from EMG recordings in the hindlimb. These probes were implanted at least 2 days before the measurements. Muscle vascular conductance (MVC = MBF/MAP) in all groups started to rise within 1 s after the onset of locomotion, but the increasing rate in CSD and BLK was significantly higher than in CNT for the first 9 s (P < 0.001). MAP in CSD and BLK significantly decreased below the baseline within 1 s and this was highly correlated with the increase in MVC for the first 9 s (R2 = 0.842, P < 0.001), whereas MAP in CNT increased significantly 8 s after the onset of locomotion. Although the total period of movement in a free-moving state for 60 min was not significantly different between CNT and CSD (P > 0.1), the frequency of movement with a short duration of 0.1–0.4 min was higher in CSD than in CNT (P < 0.001), which was highly correlated with the reduction in MAP accompanying each period of movement (R2 = 0.883, P < 0.01). These results suggest that arterial baroreflexes suppress vasodilatation in contracting muscle to maintain MAP at the onset of voluntary locomotion, and are necessary to continue a given duration of locomotion in mice. PMID:12937292

Analysis of baroreflex sensitivity during undulation pump ventricular assist device support.

PubMed

Liu, Hongjian; Shiraishi, Yasuyuki; Zhang, Xiumin; Song, Hojin; Saijo, Yoshifumi; Baba, Atsushi; Yambe, Tomoyuki; Abe, Yusuke; Imachi, Kou

2009-07-01

The aim of this study was to examine the baroreflex sensitivity (BRS), which involves the autonomic nervous system, in a goat with a chronically implanted undulation pump ventricular assist device (UPVAD). The UPVAD involved transforming the rotation of a brushless DC motor into an undulating motion by a disc attached via a special linking mechanism, and a jellyfish valve in the outflow cannula to prevent diastolic backflow. The pump was implanted into the thoracic cavity of a goat by a left thoracotomy, and the inflow and outflow cannulae were sutured to the apex of the left ventricle and to the descending aorta, respectively. The driving cable was wired percutaneously to an external controller. Electrocardiogram and hemodynamic waveforms were recorded at a sampling frequency of 1 kHz. BRS was determined when awake by the slope of the linear regression of R-R interval against mean arterial pressure changes, which were induced by the administration of methoxamine hydrochloride, both with continuous driving of the UPVAD as well as without assistance. BRS values during the UPVAD support and without assistance were 1.60 +/- 0.30 msec/mm Hg and 0.98 +/- 0.22 msec/mm Hg (n = 5, P < 0.05), respectively. BRS was significantly improved during left ventricular assistance. Therefore, UPVAD support might decrease sympathetic nerve activity and increase parasympathetic nerve activity to improve both microcirculation and organ function.

Association between aerobic fitness and indices of autonomic regulation: cardiovascular risk implications.

PubMed

Sala, Roberto; Malacarne, Mara; Pagani, Massimo; Lucini, Daniela

2016-06-01

In the general population higher levels of exercise capacity seem to protect the cardiovascular system with effects well beyond traditional risk factors. We hypothesize that this phenomenon, called "risk factor gap", could be ascribed to functional components, such as autonomic adaptation to aerobic training. In 257 subjects (age 36.2±0.8 years) we measured VO2peak (incremental cycling exercise), together with arterial pressure and autonomic proxies (baroreflex gain, R-R variance and standing induced increase in marker of excitatory oscillatory regulation of the SA node, ∆LFRRnu). Autonomic proxies appeared significantly correlated with indicators of aerobic fitness (age and gender corrected correlation between VO2peak, baroreflex gain: r=0.277, P<0.001, and DAP r=-0.228, P<0.001). Subsequently, subjects were subdivided in three age and gender adjusted categories of VO2peak (poor, medium and good). Autonomic indices and arterial pressure appeared significantly ordered with categories of VO2peak (P<0.006). In addition, within these categories the proportion of subjects with a desirable autonomic and pressure profile becomes significantly greater with better fitness levels. The strong ordered relationship between categories of aerobic fitness and autonomic proxies speaks in favor of a complementary role of the autonomic nervous system in the management of cardiovascular risk factor gap at a population level.

Differentiation in the angiotensin II receptor 1 blocker class on autonomic function.

PubMed

Krum, H

2001-09-01

Autonomic function is disordered in cardiovascular disease states such as chronic heart failure (CHF) and hypertension. Interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) may potentially occur at a number of sites. These include central sites (eg, rostral ventrolateral medulla), at the level of baroreflex control, and at the sympathetic prejunctional angiotensin II receptor 1 (AT(1)) receptor, which is facilitatory for norepinephrine release from the sympathetic nerve terminal. Therefore, drugs that block the RAAS may be expected to improve autonomic dysfunction in cardiovascular disease states. In order to test the hypothesis that RAAS inhibition directly reduces SNS activity, a pithed rat model of sympathetic stimulation has been established. In this model, an increase in frequency of stimulation results in a pressor response that is sympathetically mediated and highly reproducible. This pressor response is enhanced in the presence of angiotensin II and is reduced in the presence of nonselective AIIRAs that block both AT(1) and AT(2) receptor subtypes (eg, saralasin). AT(1)-selective antagonists have also been studied in this model, at pharmacologically relevant doses. In one such study, only the AT(1) blocker eprosartan reduced sympathetically stimulated increases in blood pressure, whereas comparable doses of losartan, valsartan, and irbesartan did not. The reason(s) for the differences between eprosartan and other agents of this class on sympathetic modulation are not clear, but may relate to the chemical structure of the drug (a non- biphenyl tetrazole structure that is chemically distinct from the structure of other AIIRAs), receptor binding characteristics (competitive), or unique effects on presynaptic AT(1) receptors.

Exaggerated cardiovascular effects of cocaine in conscious dogs with pacing-induced dilated cardiomyopathy.

PubMed

Mathier, Michael A; Shen, You-Tang; Shannon, Richard P

2002-12-01

The aim of this study was to explore the characteristics and mechanisms of the cardiovascular effects of cocaine in dilated cardiomyopathy. We studied the cardiovascular responses to acute intravenous cocaine (1 mg/kg) in 8 conscious, chronically instrumented dogs before and after the development of dilated cardiomyopathy induced by rapid ventricular pacing. To help elucidate the role of altered baroreflex function in mediating the cardiovascular effects of cocaine, we also studied responses in 3 conscious, chronically instrumented dogs that had undergone surgical sinoaortic baroreceptor denervation. Cocaine produced greater increases in heart rate (+57 +/- 8% from 112 +/- 5 beats/min versus +28 +/- 3% from 100 +/- 4 beats/min; P <.01), first derivative of left ventricular pressure (+30 +/- 5% from 1,714 +/- 147 mm Hg/sec versus +15 +/- 3% from 3,032 +/- 199 mm Hg/sec; P <.01), coronary vascular resistance (+28 +/- 5% from 2.3 +/- 0.3 mm Hg/mL/min versus +11 +/- 5% from 2.2 +/- 0.3 mm Hg/mL/min; P <.05) and plasma norepinephrine concentration (+130 +/- 31% from 462 +/- 102 pg/mL versus +86 +/- 32% from 286 +/- 77 pg/mL; P <.05) in dogs with dilated cardiomyopathy as compared to controls. In addition, responses were much more rapid in onset following the development of dilated cardiomyopathy. Chronotropic and inotropic responses to cocaine were similarly rapid and exaggerated in dogs after baroreceptor denervation. Cocaine produces rapid and exaggerated chronotropic, inotropic, and coronary vasoconstrictor responses in conscious dogs with pacing-induced dilated cardiomyopathy. Alterations in arterial baroreflex function may play a role in these observations, which in turn may underlie the clinically observed association between cocaine and heart failure.

Is autonomic modulation different between European and Chinese astronauts?

PubMed

Liu, Jiexin; Li, Yongzhi; Verheyden, Bart; Chen, Shanguang; Chen, Zhanghuang; Gai, Yuqing; Liu, Jianzhong; Gao, Jianyi; Xie, Qiong; Yuan, Ming; Li, Qin; Li, Li; Aubert, André E

2015-01-01

The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences. Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability. Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts. Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc.

Is Autonomic Modulation Different between European and Chinese Astronauts?

PubMed Central

Liu, Jiexin; Li, Yongzhi; Verheyden, Bart; Chen, Shanguang; Chen, Zhanghuang; Gai, Yuqing; Liu, Jianzhong; Gao, Jianyi; Xie, Qiong; Yuan, Ming; Li, Qin; Li, Li; Aubert, André E.

2015-01-01

Purpose The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences. Methods Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability. Results Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts. Conclusion Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc. PMID:25799561

Blood pressure responses to dietary sodium: Association with autonomic cardiovascular function in normotensive adults.

PubMed

Matthews, Evan L; Brian, Michael S; Edwards, David G; Stocker, Sean D; Wenner, Megan M; Farquhar, William B

2017-12-01

Blood pressure responses to dietary sodium vary widely person-to-person. Salt sensitive rodent models display altered autonomic function, a trait thought to contribute to poor cardiovascular health. Thus, we hypothesized that increased salt sensitivity (SS) in normotensive humans would be associated with increased muscle sympathetic nerve activity (MSNA), decreased high frequency heart rate variability (HF-HRV), and decreased baroreflex sensitivity. Healthy normotensive men and women completed 1week of high (300mmol·day -1 ) and 1week of low (20mmol·day -1 ) dietary sodium (random order) with 24h mean arterial pressure (MAP) assessed on the last day of each diet to assess SS. Participants returned to the lab under habitual sodium conditions for testing. Forty-two participants are presented in this analysis, 19 of which successful MSNA recordings were obtained (n=42: age 39±2yrs., BMI 24.3±0.5kg·(m 2 ) -1 , MAP 83±1mmHg, habitual urine sodium 93±7mmol·24h -1 ; n=19: MSNA burst frequency 20±2 bursts·min -1 ). The variables of interest were linearly regressed over the magnitude of SS. Higher SS was associated with increased MSNA (burst frequency: r=0.469, p=0.041), decreased HF-HRV (r=-0.349, p=0.046), and increased LF/HF-HRV (r=0.363, p=0.034). SS was not associated with sympathetic or cardiac baroreflex sensitivity (p>0.05). Multiple regression analysis accounting for age found that age, not SS, independently predicted HF-HRV (age adjusted no longer significant; p=0.369) and LF/HF-HRV (age adjusted p=0.273). These data suggest that age-related salt sensitivity of blood pressure in response to dietary sodium is associated with altered resting autonomic cardiovascular function. Copyright © 2017 Elsevier B.V. All rights reserved.

Static magnetic field blood pressure buffering, baroreflex vs. vascular blood pressure control mechanism.

PubMed

Gmitrov, Juraj

2010-02-01

We compared the effect of static magnetic field (SMF) and verapamil, a potent vascular calcium channel blocking agent, on sudden elevation in blood pressure in conjunction with arterial baroreflex sensitivity (BRS) and microcirculation. Forty-four experiments were performed on conscious rabbits sedated using pentobarbital intravenous (i.v.) infusion (5 mg kg(-1) h(-1)). Mean femoral artery blood pressure (MAP), heart rate, BRS and ear lobe skin microcirculatory blood flow, estimated using microphotoelectric plethysmography (MPPG), were simultaneously measured after a 40 min exposure of the sinocarotid baroreceptors to 350 mT SMF, generated by Nd(2)-Fe(14)-B magnets, or 30 min of verapamil i.v. administration (20 microg kg(-1) min(-1)). BRS was assessed from heart rate and MAP responses to i.v. bolus of nitroprusside and phenylephrine. The decrease in phenylephrine-induced abrupt elevation in MAP (DeltaMAP(AE)) was significantly larger after verapamil than after SMF exposure. DeltaMAP(AE) inversely correlated with verapamil-induced significant increase in DeltaMPPG (r = 0.53, p < 0.000) and with SMF-induced significant increase in DeltaBRS (r = 0.47, p < 0.016). Our results suggest that verapamil-potentiated vascular blood pressure buffering mechanism was more effective than SMF-potentiated baroreflex-mediated blood pressure buffering mechanism, and a potential benefit of both approaches in cardiovascular conditions with abrupt high elevation in blood pressure.

Chronic Lowering of Blood Pressure by Carotid Baroreflex Activation: Mechanisms and Potential for Hypertension Therapy

PubMed Central

Lohmeier, Thomas E.; Iliescu, Radu

2011-01-01

Recent technical advances have renewed interest in device-based therapy for the treatment of drug-resistant hypertension. Findings from recent clinical trials regarding the efficacy of electrical stimulation of the carotid sinus for the treatment of resistant hypertension are reviewed here. The main goal of this article, however, is to summarize the preclinical studies that have provided insight into the mechanisms that account for the chronic blood pressure lowering effects of carotid baroreflex activation. Some of the mechanisms identified were predictable and confirmed by experimentation. Others have been surprising and controversial and resolution will require further investigation. Although feasibility studies have been promising, firm conclusions regarding the value of this device-based therapy for the treatment of resistant hypertension awaits the results of current multicenter trials. PMID:21357283

Carotid baroreflex control of leg vasculature in exercising and non-exercising skeletal muscle in humans

PubMed Central

Melvin Keller, David; Fadel, Paul J; Ogoh, Shigehiko; Matthew Brothers, Robert; Hawkins, Megan; Olivencia-Yurvati, Al; Raven, Peter B

2004-01-01

Carotid baroreflex (CBR) function was examined in five men and three women (25 ± 1 years) using the variable-pressure neck collar technique at rest and during dynamic, one-legged knee extension exercise at 7 W and 25 W. The CBR exhibited control of leg vascular conductance (LVC) at rest and during exercise in both an exercising leg (EL) and a non-exercising leg (NEL) across a wide range of pressures from +40 Torr neck pressure (NP) to −80 Torr neck suction (NS). Specifically, increases in LVC (% change) in response to NS were no different across −20 to −80 Torr in either EL or NEL compared to rest, P > 0.05. However, CBR-mediated decreases in percentage LVC in response to NP were attenuated in EL at both 7 W (16 ± 1%) and 25 W (12 ± 1%) compared to rest (40 ± 3%; P < 0.05) as well as compared to responses in the NEL (36 ± 6% at 7 W and 36 ± 7% at 25 W; P < 0.05). This decrease in vascular responsiveness in EL was associated with a reduction in the gain of the percentage muscle sympathetic nerve activity (%MSNA)–%LVC relationship compared to rest (P < 0.05). Collectively, these data indicate that, despite a clear attenuation of the vascular response to MSNA in the exercising leg, CBR-mediated changes in mean arterial pressure were no different between rest and exercise. PMID:15388778

Cardiovascular alterations at different stages of hypertension development during ethanol consumption: Time-course of vascular and autonomic changes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crestani, Carlos C.; Lopes da Silva, Andréia; Scopinho, América A.

The aim of the present work was to establish a time-course correlation between vascular and autonomic changes that contribute to the development of hypertension during ethanol ingestion in rats. For this, male Wistar rats were subjected to the intake of increasing ethanol concentrations in their drinking water during four weeks. Ethanol effects were investigated at the end of each week. Mild hypertension was already observed at the first week of treatment, and a progressive blood pressure increase was observed along the evaluation period. Increased pressor response to phenylephrine was observed from first to fourth week. α{sub 1}-adrenoceptor protein in themore » mesenteric bed was enhanced at the first week, whereas β{sub 2}-adrenoceptor protein in the aorta was reduced after the second week. In the third week, ethanol intake facilitated the depressor response to sodium nitroprusside, whereas in the fourth week it reduced nitrate content in aorta and increased it plasma. The bradycardic component of the baroreflex was impaired, whereas baroreflex tachycardia was enhanced at the third and fourth weeks. AT{sub 1A} receptor and C-type natriuretic peptide (CNP) mRNAs in the nucleus tractus solitarius were increased at the fourth week. These findings suggest that increased vascular responsiveness to vasoconstrictor agents is possibly a link factor in the development and maintenance of the progressive hypertension induced by ethanol consumption. Additionally, baroreflex changes are possibly mediated by alterations in angiotensinergic mechanisms and CNP content within the brainstem, which contribute to maintaining the hypertensive state in later phases of ethanol ingestion. Facilitated vascular responsiveness to nitric oxide seems to counteract ethanol-induced hypertension. - Highlights: • Mild hypertension was observed during the entire period of ethanol ingestion. • Ethanol facilitated vascular reactivity to vasoactive agents. • Changes in baroreflex activity contribute to ethanol-evoked hypertension. • Plasma and aortic nitrate content was affected by ethanol consumption. • Ethanol changed AT{sub 1A} receptor and CNP in the nucleus tractus solitaries.« less

Magnitude of Morning Surge in Blood Pressure Is Associated with Sympathetic but Not Cardiac Baroreflex Sensitivity

PubMed Central

Johnson, Aaron W.; Hissen, Sarah L.; Macefield, Vaughan G.; Brown, Rachael; Taylor, Chloe E.

2016-01-01

The ability of the arterial baroreflex to regulate blood pressure may influence the magnitude of the morning surge in blood pressure (MSBP). The aim was to investigate the relationships between sympathetic and cardiac baroreflex sensitivity (BRS) and the morning surge. Twenty-four hour ambulatory blood pressure was recorded in 14 young individuals. The morning surge was defined via the pre-awakening method, which is calculated as the difference between mean blood pressure values 2 h before and 2 h after rising from sleep. The mean systolic morning surge, diastolic morning surge, and morning surge in mean arterial pressures were 15 ± 2, 13 ± 1, and 11 ± 1 mmHg, respectively. During the laboratory protocol, continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made over a 10-min period of rest. Sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (sympathetic BRStotal). Cardiac BRS was quantified using the sequence method. The mean values for sympathetic BRSinc, sympathetic BRStotal and cardiac BRS were −1.26 ± 0.26 bursts/100 hb/mmHg, −1.60 ± 0.37 AU/beat/mmHg, and 13.1 ± 1.5 ms/mmHg respectively. Significant relationships were identified between sympathetic BRSinc and the diastolic morning surge (r = 0.62, p = 0.02) and the morning surge in mean arterial pressure (r = 0.57, p = 0.03). Low sympathetic BRS was associated with a larger morning surge in mean arterial and diastolic blood pressure. Trends for relationships were identified between sympathetic BRStotal and the diastolic morning surge (r = 0.52, p = 0.066) and the morning surge in mean arterial pressure (r = 0.48, p = 0.095) but these did not reach significance. There were no significant relationships between cardiac BRS and the morning surge. These findings indicate that the ability of the baroreflex to buffer increases in blood pressure via reflexive changes in MSNA may play a role in determining the magnitude of the MSBP. PMID:27660603

Rosiglitazone Improves Insulin Sensitivity and Baroreflex Gain in Rats with Diet-Induced Obesity

PubMed Central

Zhao, Ding; McCully, Belinda H.

2012-01-01

Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that impaired BRG is related to the concurrent insulin resistance, and, therefore, BRG would be improved after treatment with the insulin-sensitizing drug rosiglitazone. Male rats fed a high-fat diet diverged into obesity-prone (OP) and obesity-resistant (OR) groups after 2 weeks. Then, OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily for 2 to 3 weeks with rosiglitazone (3 or 6 mg/kg) or its vehicle by gavage. Compared with OR and CON rats, conscious OP rats exhibited reductions in BRG (OP, 2.9 ± 0.1 bpm/mm Hg; OR, 4.0 ± 0.2 bpm/mm Hg; CON, 3.9 ± 0.2 bpm/mm Hg; P < 0.05) and insulin sensitivity (hyperinsulinemic euglycemic clamp; OP, 6.8 ± 0.9 mg/kg · min; OR, 22.2 ± 1.2 mg/kg · min; CON, 17.7 ± 0.8 mg/kg · min; P < 0.05), which were well correlated (r2 = 0.49; P < 0.01). In OP rats, rosiglitazone dose-dependently improved (P < 0.05) insulin sensitivity (12.8 ± 0.6 mg/kg · min at 3 mg/kg; 16.0 ± 1.5 mg/kg · min at 6 mg/kg) and BRG (3.8 ± 0.4 bpm/mm Hg at 3 mg/kg; 5.3 ± 0.7 bpm/mm Hg at 6 mg/kg). However, 6 mg/kg rosiglitazone also increased BRG in OR rats without increasing insulin sensitivity, disrupted the correlation between BRG and insulin sensitivity (r2 = 0.08), and, in OP and OR rats, elevated BRG relative to insulin sensitivity (analysis of covariance; P < 0.05). Moreover, in OP rats, stimulation of the aortic depressor nerve, to activate central baroreflex pathways, elicited markedly reduced decreases in heart rate and arterial pressure, but these responses were not improved by rosiglitazone. In conclusion, diet-induced obesity impairs BRG via a central mechanism that is related to the concurrent insulin resistance. Rosiglitazone normalizes BRG, but not by improving brain baroreflex processing or insulin sensitivity. PMID:22815534

Baroreflex Sensitivity Decreases During 90-Day Bed Rest

NASA Technical Reports Server (NTRS)

Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

2008-01-01

Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

The carotid baroreflex modifies the pressor threshold of the muscle metaboreflex in humans.

PubMed

Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Watanabe, Kazuhito; Kondo, Narihiko; Nishiyasu, Takeshi

2017-09-01

The purpose of the present study was to test our hypothesis that unloading the carotid baroreceptors alters the threshold and gain of the muscle metaboreflex in humans. Ten healthy subjects performed a static handgrip exercise at 50% of maximum voluntary contraction. Contraction was sustained for 15, 30, 45, and 60 s and was followed by 3 min of forearm circulatory arrest, during which forearm muscular pH is known to decrease linearly with increasing contraction time. The carotid baroreceptors were unloaded by applying 0.1-Hz sinusoidal neck pressure (oscillating from +15 to +50 mmHg) during ischemia. We estimated the threshold and gain of the muscle metaboreflex by analyzing the relationship between the cardiovascular responses during ischemia and the amount of work done during the exercise. In the condition with unloading of the carotid baroreceptors, the muscle metaboreflex thresholds for mean arterial blood pressure (MAP) and total vascular resistance (TVR) corresponded to significantly lower work levels than the control condition (threshold for MAP: 795 ± 102 vs. 662 ± 208 mmHg and threshold for TVR: 818 ± 213 vs. 572 ± 292 kg·s, P < 0.05), but the gains did not differ between the two conditions (gain for MAP: 4.9 ± 1.7 vs. 4.4 ± 1.6 mmHg·kg·s -1 ·100 and gain for TVR: 1.3 ± 0.8 vs. 1.3 ± 0.7 mmHg·l -1 ·min -1 ·kg·s -1 ·100). We conclude that the carotid baroreflex modifies the muscle metaboreflex threshold in humans. Our results suggest the carotid baroreflex brakes the muscle metaboreflex, thereby inhibiting muscle metaboreflex-mediated pressor and vasoconstriction responses. NEW & NOTEWORTHY We found that unloading the carotid baroreceptors shifts the pressor threshold of the muscle metaboreflex toward lower metabolic stimulation levels in humans. This finding indicates that, in the normal loading state, the carotid baroreflex inhibits the muscle metaboreflex pressor response by shifting the reflex threshold to higher metabolic stimulation levels. Copyright © 2017 the American Physiological Society.

RAS in the central nervous system: Potential role in neuropsychiatric disorders.

PubMed

Rocha, Natalia Pessoa; Simões e Silva, Ana Cristina; Prestes, Thiago Ruiz Rodrigues; Feracin, Victor; Machado, Caroline Amaral; Ferreira, Rodrigo Novaes; Teixeira, Antonio Lucio; de Miranda, Aline Silva

2018-02-25

The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders of the modulation of RAS. We carried out an extensive literature search in PubMed central. Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and haemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Brain-Targeted (Pro)Renin Receptor Knockdown attenuates Angiotensin II-Dependent Hypertension

PubMed Central

Li, Wencheng; Peng, Hua; Cao, Theresa; Sato, Ryosuke; McDaniels, Sarah. J.; Kobori, Hiroyuki; Navar, L. Gabriel; Feng, Yumei

2012-01-01

The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor shRNA was used to knockdown (pro)renin receptor expression in the brain of non-transgenic normotensive and human renin-angiotensinogen double transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor and vasopressin mRNA levels. Plasma vasopressin levels were determined by Enzyme-Linked Immuno Sorbent Assay. Double transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor shRNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared to the control virus treatment in double transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease insympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with down-regulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice. PMID:22526255

Effect of sodium intake on sympathetic and hemodynamic response to thermal receptor stimulation.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-02-01

Low dietary sodium intake increases central nervous system angiotensin activity, which increases basal renal sympathetic nerve activity and shifts its arterial baroreflex control to a higher level of arterial pressure. This results in a higher level of renal sympathetic nerve activity for a given level of arterial pressure during low dietary sodium intake than during either normal or high dietary sodium intake, in which there is less central angiotensin activity. Peripheral thermal receptor stimulation overrides arterial baroreflex control and produces a pressor response, tachycardia, increased renal sympathetic nerve activity, and renal vasoconstriction. To test the hypothesis that increased central angiotensin activity would enhance the responses to peripheral thermal receptor stimulation, anesthetized normal rats in balance on low, normal, and high dietary sodium intake were subjected to acute peripheral thermal receptor stimulation. Low sodium rats had greater increases in renal sympathetic nerve activity, greater decreases in RBF, and greater increases in renal vascular resistance than high sodium rats. Responses of normal sodium rats were between those of low and high sodium rats. Arterial pressure and heart rate responses were not different among dietary groups. Spontaneously hypertensive rats, known to have increased central nervous system angiotensin activity, also had greater renal sympathoexcitatory and vasoconstrictor responses than normotensive Wistar-Kyoto rats. These results support the view that increased central nervous system angiotensin activity alters arterial baroreflex control of renal sympathetic nerve activity such that the renal sympathoexcitatory and vasoconstrictor responses to peripheral thermoreceptor stimulation are enhanced.

Modeling the Afferent Dynamics of the Baroreflex Control System

PubMed Central

Mahdi, Adam; Sturdy, Jacob; Ottesen, Johnny T.; Olufsen, Mette S.

2013-01-01

In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation of mechanoreceptors located in the BR nerve-endings, and modulation of the action potential frequency. The three sub-systems are modeled individually following well-established biological principles. The first submodel, predicting arterial wall deformation, uses blood pressure as an input and outputs circumferential strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate on pressure can be accounted for by taking into account the nonlinear elastic properties of the artery wall. This was observed when testing the models using multiple experiments with a single set of parameters. We find that to model the response to a square pressure stimulus, giving rise to post-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we demonstrate that our preferred model can exhibit all known dynamics and that it is advantageous to combine qualitative and quantitative analysis methods. PMID:24348231

TRPC5 channels participate in pressure-sensing in aortic baroreceptors

PubMed Central

Lau, On-Chai; Shen, Bing; Wong, Ching-On; Tjong, Yung-Wui; Lo, Chun-Yin; Wang, Hui-Chuan; Huang, Yu; Yung, Wing-Ho; Chen, Yang-Chao; Fung, Man-Lung; Rudd, John Anthony; Yao, Xiaoqiang

2016-01-01

Blood pressure is maintained within a normal physiological range by a sophisticated regulatory mechanism. Baroreceptors serve as a frontline sensor to detect the change in blood pressure. Nerve signals are then sent to the cardiovascular control centre in the brain in order to stimulate baroreflex responses. Here, we identify TRPC5 channels as a mechanical sensor in aortic baroreceptors. In Trpc5 knockout mice, the pressure-induced action potential firings in the afferent nerve and the baroreflex-mediated heart rate reduction are attenuated. Telemetric measurements of blood pressure demonstrate that Trpc5 knockout mice display severe daily blood pressure fluctuation. Our results suggest that TRPC5 channels represent a key pressure transducer in the baroreceptors and play an important role in maintaining blood pressure stability. Because baroreceptor dysfunction contributes to a variety of cardiovascular diseases including hypertension, heart failure and myocardial infarction, our findings may have important future clinical implications. PMID:27411851

Arterial Stiffness and Autonomic Modulation After Free-Weight Resistance Exercises in Resistance Trained Individuals.

PubMed

Kingsley, J Derek; Mayo, Xián; Tai, Yu Lun; Fennell, Curtis

2016-12-01

Kingsley, JD, Mayo, X, Tai, YL, and Fennell, C. Arterial stiffness and autonomic modulation after free-weight resistance exercises in resistance trained individuals. J Strength Cond Res 30(12): 3373-3380, 2016-We investigated the effects of an acute bout of free-weight, whole-body resistance exercise consisting of the squat, bench press, and deadlift on arterial stiffness and cardiac autonomic modulation in 16 (aged 23 ± 3 years; mean ± SD) resistance-trained individuals. Arterial stiffness, autonomic modulation, and baroreflex sensitivity (BRS) were assessed at rest and after 3 sets of 10 repetitions at 75% 1-repetition maximum on each exercise with 2 minutes of rest between sets and exercises. Arterial stiffness was analyzed using carotid-femoral pulse wave velocity (cf-PWV). Linear heart rate variability (log transformed [ln] absolute and normalized units [nu] of low-frequency [LF] and high-frequency [HF] power) and nonlinear heart rate complexity (Sample Entropy [SampEn], Lempel-Ziv Entropy [LZEn]) were measured to determine autonomic modulation. BRS was measured by the sequence method. A 2 × 2 repeated measures analysis of variance (ANOVA) was used to analyze time (rest, recovery) across condition (acute resistance exercise, control). There were significant increases in cf-PWV (p = 0.05), heart rate (p = 0.0001), normalized LF (LFnu; p = 0.001), and the LF/HF ratio (p = 0.0001). Interactions were also noted for ln HF (p = 0.006), HFnu (p = 0.0001), SampEn (p = 0.001), LZEn (p = 0.005), and BRS (p = 0.0001) such that they significantly decreased during recovery from the resistance exercise compared with rest and the control. There was no effect on ln total power, or ln LF. These data suggest that a bout of resistance exercise using free-weights increases arterial stiffness and reduces vagal activity and BRS in comparison with a control session. Vagal tone may not be fully recovered up to 30 minutes after a resistance exercise bout.

Determinants of muscle metaboreflex and involvement of baroreflex in boys and young men.

PubMed

Dipla, Konstantina; Papadopoulos, Stavros; Zafeiridis, Andreas; Kyparos, Antonios; Nikolaidis, Michalis G; Vrabas, Ioannis S

2013-04-01

This study aimed to assess the arterial pressure (AP) determinants during the muscle metaboreflex in boys and men and to investigate the contribution of baroreflex and sympathovagal function to the metaboreflex-induced responses. Fourteen pre-adolescent boys and 13 men performed a protocol involving: baseline, isometric handgrip exercise, circulatory occlusion, and recovery. The same protocol was repeated without occlusion. During baseline, boys had lower beat-to-beat AP, higher heart rate (HR), and lower low/high frequency HR variability. During exercise, a parasympathetic withdrawal was evident in both groups. In adults, HR was the key contributor to the pressure response, with no changes in stroke volume, whereas in boys, the lower HR increase was counterbalanced by an increase in stroke volume, resulting in similar relative increases in AP in both groups. In recovery, boys exhibited a faster rate of HR-decay, rapid vagal reactivation, and greater decrease in TPR than men. An overshoot in baroreceptor sensitivity was observed in men. The isolated metaboreflex resulted in a similar AP elevation in both age groups (by ~15 mmHg), and attenuated spontaneous baroreceptor sensitivity. However, during the metaboreflex, pre-adolescent males exhibited a lower increase in peripheral resistance and a greater bradycardic response than adults, and a fast restoration of vagal activity to non-occlusion levels. During metaboreflex, boys were capable of eliciting a pressure response similar to the one elicited by men; however, the interplay of the mechanisms underlying the rise in AP differed between the two groups with the vagal contribution being greater in the younger participants.

Eppur Si Muove: The Dynamic Nature of Physiological Control of Renal Blood Flow by the Renal Sympathetic Nerves

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter Ricci; Zucker, Irving H.

2016-01-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. PMID:27514571

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

PubMed

Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

2017-05-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

βENaC is a molecular component of a VSMC mechanotransducer that contributes to renal blood flow regulation, protection from renal injury, and hypertension.

PubMed

Drummond, Heather A

2012-01-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechano-dependent response in certain blood vessels. The response is mediated by vascular smooth muscle cells (VSMCs) and characterized by a pressure-induced vasoconstriction in small arteries and arterioles in the cerebral, mesenteric, cardiac, and renal beds. The myogenic response has two important roles; it is a mechanism of blood flow autoregulation and provides protection against systemic blood pressure-induced damage to delicate microvessels. However, the molecular mechanism(s) underlying initiation of myogenic response is unclear. Degenerin proteins have a strong evolutionary link to mechanotransduction in the nematode. Our laboratory has addressed the hypothesis that these proteins may also act as mechanosensors in certain mammalian tissues such as VSMCs and arterial baroreceptor neurons. This article discusses the importance of a specific degenerin protein, β Epithelial Na(+) Channel (βENaC) in pressure-induced vasoconstriction in renal vessels and arterial baroreflex function as determined in a mouse model of reduced βENaC (βENaC m/m). We propose that loss of baroreflex sensitivity (due to loss of baroreceptor βENaC) increases blood pressure variability, increasing the likelihood and magnitude of upward swings in systemic pressure. Furthermore, loss of the myogenic constrictor response (due to loss of VSMC βENaC) will permit those pressure swings to be transmitted to the microvasculature in βENaC m/m mice, thus increasing the susceptibility to renal injury and hypertension.

Brain ACE2 shedding contributes to the development of neurogenic hypertension

PubMed Central

Chhabra, Kavaljit H.; Lazartigues, Eric

2015-01-01

Rationale Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. Objective We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. Methods and Results To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. Conclusions Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension. PMID:24014829

Reduced Baroreflex Sensitivity in Cluster Headache Patients.

PubMed

Barloese, Mads C J; Mehlsen, Jesper; Brinth, Louise; Lundberg, Helena I S; Jennum, Poul J; Jensen, Rigmor H

2015-06-01

Important elements of cluster headache (CH) pathophysiology may be seated in the posterior hypothalamus. Cranial autonomic features are inherent, but involvement of systemic autonomic control is still debated. We aimed to characterize autonomic function as investigated by baroreflex sensitivity (BRS) in CH patients. Twenty-six active CH patients and an equal number of age-, sex-, and BMI-matched controls underwent head-up tilt table test and BRS was determined by the sequence method. Compared with controls, patients exhibited a blunted reactivity of RR intervals in response to falls and increases in systolic blood pressure (SBP) (15.3 vs. 20.0 ms/mmHg, P = .0041) in the supine position. Also, compared with controls, BRS was lower in patients having suffered an attack within the past 12 hours (n = 13, 12.5 vs. 22.3 ms/mmHg, P = .0091), opposed to those patients who had not (n = 13, 16.0 ms/mmHg, P = .1523). In the tilted position, the drop in SBP at the carotid sinuses was higher in patients who had recently suffered an attack. Despite this, they exhibited a less marked shortening of RR intervals when compared with patients who had been attack free for longer. CH patients exhibit a subclinical blunting of BRS that may be affected by the attacks themselves. The fast RR interval fluctuations used in this method reflects cardiovagal responses, thus the blunted responses are suggestive of dysfunction in the parasympathetic division of the autonomic nervous system or in the central relay of impulses from the baroreceptors. © 2015 American Headache Society.

CHRONIC HYPERTENSION ENHANCES PRE-SYNAPTIC INHIBITION BY BACLOFEN IN THE NUCLEUS OF THE SOLITARY TRACT

PubMed Central

Zhang, Weirong; Mifflin, Steve

2010-01-01

The selective γ-aminobutyric acid B-subtype receptor agonist baclofen activates both pre- and post-synaptic receptors in the brain. Microinjection of baclofen into the nucleus of the solitary tract increases arterial pressure, heart rate and sympathetic nerve discharge consistent with inhibition of the arterial baroreflex. The magnitude of these responses is enhanced in hypertension and is associated with increased post-synaptic GABAB receptor function. We tested whether a pre-synaptic mechanism contributes to the enhanced baclofen inhibition in hypertension. Whole-cell recordings of second-order baroreceptor neurons, identified by 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide labeling of aortic nerve, were obtained in brainstem slices from normotensive control and renal-wrap hypertensive rats. After 4 weeks, arterial blood pressure was 162±9 mmHg in hypertensive (n=6) and 107±3 mmHg in control rats (n=6/11, p<0.001). Baclofen reduced the amplitude of excitatory post-synaptic currents evoked by solitary tract stimulation and the EC50 of this inhibition was greater in control (1.5±0.5 µmol/L, n=6) than hypertensive cells (0.6±0.1 µmol/L, n=9, p<0.05). Baclofen (1 µmol/L) elicited greater inhibition on evoked response in hypertensive (58±6%, n=9) than control cells (40±6%, n=8, p<0.05). Another index of pre-synaptic inhibition, the paired-pulse ratio (ratio of second to first evoked response amplitudes at stimulus intervals of 40 ms), was greater in hypertensive (0.60±0.08, n=8) than control cells (0.48±0.06. n=5, p<0.05). The results suggest that in renal-wrap hypertensive rats, baclofen causes an enhanced pre-synaptic inhibition of glutamate release from baroreceptor afferent terminals to second-order neurons in the nucleus of the solitary tract. This enhanced pre-synaptic inhibition could contribute to altered baroreflex function in hypertension. PMID:20038748

Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors.

PubMed

Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2014-06-13

This study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3 V, 20-100 Hz) or C-fiber (20 V, 0-10 Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28 ± 0.04 vs. 4.01 ± 0.2%·Hz(-1), P<0.001) and coherence at 0.01 Hz (0.44 ± 0.05 vs. 0.81 ± 0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82 ± 1.02 vs. 7.21 ± 0.79 dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23 ± 0.05 vs. 3.05 ± 0.31 mmHg·Hz(-1), P<0.001). These data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

A diminished aortic-cardiac reflex during hypotension in aerobically fit young men

NASA Technical Reports Server (NTRS)

Shi, X.; Crandall, C. G.; Potts, J. T.; Williamson, J. W.; Foresman, B. H.; Raven, P. B.

1993-01-01

We compared the aortic-cardiac baroreflex sensitivity in eight average fit (AF: VO2max = 44.7 +/- 1.3 ml.kg-1 x min-1) and seven high fit (HF: VO2max = 64.1 +/- 1.7 ml.min-1 x kg-1) healthy young men during hypotension elicited by steady state sodium nitroprusside (SN) infusion. During SN mean arterial pressure (MAP) was similarly decreased in AF (-12.6 +/- 1.0 mm Hg) and HF (-12.1 +/- 1.1 mm Hg). However, the increases in heart rate (HR) were less (P < 0.023) in HF (15 +/- 3 bpm) than AF (25 +/- 1 bpm). When sustained neck suction (NS, -22 +/- 1 torr in AF and -20 +/- 1 torr in HF, P > 0.05) was applied to counteract the decreased carotid sinus transmural pressure during SN, thereby isolating the aortic baroreceptors, the increased HR remained less (P < 0.021) in HF (8 +/- 2 bpm) than AF (16 +/- 2 bpm). During both SN infusion and SN+NS, the calculated gains (i.e., delta HR/delta MAP) were significantly greater in AF (2.1 +/- 0.3 and 1.3 +/- 0.2 bpm.mm Hg-1) than HF (1.2 +/- 0.2 and 0.6 +/- 0.2 bpm.mm Hg-1). However, the estimated carotid-cardiac baroreflex sensitivity (i.e., the gain difference between the stage SN and SN + NS) was not different between AF (0.7 +/- 0.2 bpm.mm Hg-1) and HF (0.6 +/- 0.1 bpm.mm Hg-1). These data indicated that the aortic-cardiac baroreflex sensitivity during hypotension was significantly diminished with endurance exercise training.

Sodium intake influences hemodynamic and neural responses to angiotensin receptor blockade in rostral ventrolateral medulla.

PubMed

DiBona, G F; Jones, S Y

2001-04-01

To determine the effects of physiological alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity (RSNA) and its arterial baroreflex regulation, angiotensin II type 1 receptor antagonists were microinjected into the rostral ventrolateral medulla of anesthetized rats consuming a low, normal, or high sodium diet that were instrumented for simultaneous measurement of arterial pressure and RSNA. Plasma renin activity was increased in rats fed a low sodium diet and decreased in those fed a high sodium diet. Losartan (50, 100, and 200 pmol) decreased heart rate and RSNA (but not mean arterial pressure) dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a high sodium diet. Candesartan (1, 2, and 10 pmol) decreased mean arterial pressure, heart rate, and RSNA dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a normal or high sodium diet. [D-Ala(7)]Angiotensin-(1-7) (100, 200, and 1000 pmol) did not affect mean arterial pressure, heart rate, or RSNA in rats fed either a low or a high sodium diet. In rats fed a low sodium diet, candesartan reset the arterial baroreflex control of RSNA to a lower level of arterial pressure, and in rats with congestive heart failure, candesartan increased the arterial baroreflex gain of RSNA. Physiological alterations in the endogenous activity of the renin-angiotensin system influence the bradycardic, vasodepressor, and renal sympathoinhibitory responses to rostral ventrolateral medulla injection of antagonists to angiotensin II type 1 receptors but not to angiotensin-(1-7) receptors.

Impaired sympathetic vascular regulation in humans after acute dynamic exercise

NASA Technical Reports Server (NTRS)

Halliwill, J. R.; Taylor, J. A.; Eckberg, D. L.

1996-01-01

1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena.

Heart rate complexity in sinoaortic-denervated mice.

PubMed

Silva, Luiz Eduardo V; Rodrigues, Fernanda Luciano; de Oliveira, Mauro; Salgado, Hélio Cesar; Fazan, Rubens

2015-02-01

What is the central question of this study? New measurements for cardiovascular complexity, such as detrended fluctuation analysis (DFA) and multiscale entropy (MSE), have been shown to predict cardiovascular outcomes. Given that cardiovascular diseases are accompanied by autonomic imbalance and decreased baroreflex sensitivity, the central question is: do baroreceptors contribute to cardiovascular complexity? What is the main finding and its importance? Sinoaortic denervation altered both DFA scaling exponents and MSE, indicating that both short- and long-term mechanisms of complexity are altered in sinoaortic denervated mice, resulting in a loss of physiological complexity. These results suggest that the baroreflex is a key element in the complex structures involved in heart rate variability regulation. Recently, heart rate (HR) oscillations have been recognized as complex behaviours derived from non-linear processes. Physiological complexity theory is based on the idea that healthy systems present high complexity, i.e. non-linear, fractal variability at multiple scales, with long-range correlations. The loss of complexity in heart rate variability (HRV) has been shown to predict adverse cardiovascular outcomes. Based on the idea that most cardiovascular diseases are accompanied by autonomic imbalance and a decrease in baroreflex sensitivity, we hypothesize that the baroreflex plays an important role in complex cardiovascular behaviour. Mice that had been subjected to sinoaortic denervation (SAD) were implanted with catheters in the femoral artery and jugular vein 5 days prior to the experiment. After recording the baseline arterial pressure (AP), pulse interval time series were generated from the intervals between consecutive values of diastolic pressure. The complexity of the HRV was determined using detrended fluctuation analysis and multiscale entropy. The detrended fluctuation analysis α1 scaling exponent (a short-term index) was remarkably decreased in the SAD mice (0.79 ± 0.06 versus 1.13 ± 0.04 for the control mice), whereas SAD slightly increased the α2 scaling exponent (a long-term index; 1.12 ± 0.03 versus 1.04 ± 0.02 for control mice). In the SAD mice, the total multiscale entropy was decreased (13.2 ± 1.3) compared with the control mice (18.9 ± 1.4). In conclusion, fractal and regularity structures of HRV are altered in SAD mice, affecting both short- and long-term mechanisms of complexity, suggesting that the baroreceptors play a considerable role in the complex structure of HRV. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Extended duration orbiter medical project variability of blood pressure and heart rate (STS-50/USML-1)

NASA Technical Reports Server (NTRS)

Fritsch-Yelle, Janice M.; Charles, John B.; Boettcher, Sheila W.

1994-01-01

Decreases in arterial baroreflex function after space flight may be related to changes in blood pressure and heart rate patterns during flight. Ambulatory blood pressure and heart rate were measured for 24 hours, in fourteen astronauts on two occasions before flight, two to three occasions in flight, and 2 days after landing on Shuttle missions lasting 4 to 14 days. Blood pressure and heart rate were recorded every 20minutes during awake periods and every 30 minutes during sleep. In pre- and postflight studies, the 24-hour ambulatory measurements were followed by studies of carotid baroreceptor-cardiac reflex responses. Carotid baroreceptors were stimulated using a sequence of neck pressure and suction from +40 to -65 mmHg.

Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

PubMed

Iwasaki, Ken-Ichi; Zhang, Rong; Zuckerman, Julie H; Levine, Benjamin D

2003-10-01

Occupational or recreational exercise reduces mortality from cardiovascular disease. The potential mechanisms for this reduction may include changes in blood pressure (BP) and autonomic control of the circulation. Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP. We measured steady-state hemodynamics and analyzed dynamic cardiovascular regulation by spectral and transfer function analysis of cardiovascular variability in 11 initially sedentary subjects during 1 yr of progressive endurance training sufficient to allow them to complete a marathon. From this, we found that 1) moderate exercise training for 3 mo decreased BP, HR, and total peripheral resistance, and increased cardiovascular variability and arterial baroreflex sensitivity; 2) more prolonged and intense training did not augment these changes further; and 3) most of these changes returned to control values at 12 mo despite markedly increased training duration and intensity equivalent to that routinely observed in competitive athletes. In conclusion, increases in R-wave-R-wave interval and cardiovascular variability indexes are consistent with an augmentation of vagal modulation of HR after exercise training. It appears that moderate doses of training for 3 mo are sufficient to achieve this response as well as a modest hypotensive effect from decreasing vascular resistance. However, more prolonged and intense training does not necessarily lead to greater enhancement of circulatory control and, therefore, may not provide an added protective benefit via autonomic mechanisms against death by cardiovascular disease.

Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command.

PubMed

Doherty, Connor J; Incognito, Anthony V; Notay, Karambir; Burns, Matthew J; Slysz, Joshua T; Seed, Jeremy D; Nardone, Massimo; Burr, Jamie F; Millar, Philip J

2018-01-01

The contribution of central command to the peripheral vasoconstrictor response during exercise has been investigated using primarily handgrip exercise. The purpose of the present study was to compare muscle sympathetic nerve activity (MSNA) responses during passive (involuntary) and active (voluntary) zero-load cycling to gain insights into the effects of central command on sympathetic outflow during dynamic exercise. Hemodynamic measurements and contralateral leg MSNA (microneurography) data were collected in 18 young healthy participants at rest and during 2 min of passive and active zero-load one-legged cycling. Arterial baroreflex control of MSNA burst occurrence and burst area were calculated separately in the time domain. Blood pressure and stroke volume increased during exercise ( P < 0.0001) but were not different between passive and active cycling ( P > 0.05). In contrast, heart rate, cardiac output, and total vascular conductance were greater during the first and second minute of active cycling ( P < 0.001). MSNA burst frequency and incidence decreased during passive and active cycling ( P < 0.0001), but no differences were detected between exercise modes ( P > 0.05). Reductions in total MSNA were attenuated during the first ( P < 0.0001) and second ( P = 0.0004) minute of active compared with passive cycling, in concert with increased MSNA burst amplitude ( P = 0.02 and P = 0.005, respectively). The sensitivity of arterial baroreflex control of MSNA burst occurrence was lower during active than passive cycling ( P = 0.01), while control of MSNA burst strength was unchanged ( P > 0.05). These results suggest that central feedforward mechanisms are involved primarily in modulating the strength, but not the occurrence, of a sympathetic burst during low-intensity dynamic leg exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity burst frequency decreased equally during passive and active cycling, but reductions in total muscle sympathetic nerve activity were attenuated during active cycling. These results suggest that central command primarily regulates the strength, not the occurrence, of a muscle sympathetic burst during low-intensity dynamic leg exercise.

Sex Differences in Cardiac Baroreflex Sensitivity after Isometric Handgrip Exercise.

PubMed

Teixeira, André L; Ritti-Dias, Raphael; Antonino, Diego; Bottaro, Martim; Millar, Philip J; Vianna, Lauro C

2018-04-01

This study aimed to investigate potential sex-related differences on spontaneous cardiac baroreflex sensitivity (cBRS) after acute isometric handgrip (IHG) exercise. Twenty men (age, 23 ± 3 yr) and 20 women (age, 24 ± 4 yr) randomly performed four sets of 2-min IHG exercise (two sets for each limb) at 30% maximal voluntary contraction (experimental) or 3% maximal voluntary contraction (sham). Beat-to-beat heart rate (HR) and arterial blood pressure (BP) were monitored using finger photoplethysmography before and 10, 20, and 30 min after IHG. Spontaneous cBRS was assessed via the sequence technique and cardiac autonomic modulation via time- and frequency-domain HR variability. After IHG, spontaneous cBRS increased during 10 min of recovery in men (Δ13% ± 5%, P = 0.03 vs rest) and increased further in women (Δ23% ± 4%, P < 0.01 vs rest; P = 0.04 vs men). During 20 and 30 min of recovery, cBRS returned to baseline in men but remained elevated in women. HR decreased 10 min after IHG in men (10 min: Δ-2 ± 1 bpm, P < 0.01 vs rest; 20 min: Δ-1 ± 1 bpm, P = 0.39 vs rest; 30 min: Δ1 ± 1 bpm, P = 0.31 vs rest) and throughout recovery in women (10 min: Δ-5 ± 1 bpm, P < 0.01 vs rest; 20 min: Δ-3 ± 1 bpm, P < 0.01 vs rest; 30 min: Δ-2 ± 1 bpm, P < 0.01 vs rest). Systolic BP increased 10 min after IHG and remained elevated during 20 min and 30 min in men (P < 0.05). In women, systolic BP increased during 10 min (P < 0.01) and returned to baseline during 20 and 30 min of recovery. Time-domain HR variability (root mean square of successive differences) was increased during recovery in men and women (P < 0.05). Sham had no effect on any variables. Acute IHG exercise increases cBRS and cardiac vagal activity in healthy young subjects, but the magnitude and the time course of changes in cBRS differ between men and women.

Human responses to upright tilt: a window on central autonomic integration

NASA Technical Reports Server (NTRS)

Cooke, W. H.; Hoag, J. B.; Crossman, A. A.; Kuusela, T. A.; Tahvanainen, K. U.; Eckberg, D. L.

1999-01-01

1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Human responses to upright tilt: a window on central autonomic integration.

PubMed

Cooke, W H; Hoag, J B; Crossman, A A; Kuusela, T A; Tahvanainen, K U; Eckberg, D L

1999-06-01

1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Baroreflex Coupling Assessed by Cross-Compression Entropy

PubMed Central

Schumann, Andy; Schulz, Steffen; Voss, Andreas; Scharbrodt, Susann; Baumert, Mathias; Bär, Karl-Jürgen

2017-01-01

Estimating interactions between physiological systems is an important challenge in modern biomedical research. Here, we explore a new concept for quantifying information common in two time series by cross-compressibility. Cross-compression entropy (CCE) exploits the ZIP data compression algorithm extended to bivariate data analysis. First, time series are transformed into symbol vectors. Symbols of the target time series are coded by the symbols of the source series. Uncoupled and linearly coupled surrogates were derived from cardiovascular recordings of 36 healthy controls obtained during rest to demonstrate suitability of this method for assessing physiological coupling. CCE at rest was compared to that of isometric handgrip exercise. Finally, spontaneous baroreflex interaction assessed by CCEBRS was compared between 21 patients suffering from acute schizophrenia and 21 matched controls. The CCEBRS of original time series was significantly higher than in uncoupled surrogates in 89% of the subjects and higher than in linearly coupled surrogates in 47% of the subjects. Handgrip exercise led to sympathetic activation and vagal inhibition accompanied by reduced baroreflex sensitivity. CCEBRS decreased from 0.553 ± 0.030 at rest to 0.514 ± 0.035 during exercise (p < 0.001). In acute schizophrenia, heart rate, and blood pressure were elevated. Heart rate variability indicated a change of sympathovagal balance. The CCEBRS of patients with schizophrenia was reduced compared to healthy controls (0.546 ± 0.042 vs. 0.507 ± 0.046, p < 0.01) and revealed a decrease of blood pressure influence on heart rate in patients with schizophrenia. Our results indicate that CCE is suitable for the investigation of linear and non-linear coupling in cardiovascular time series. CCE can quantify causal interactions in short, noisy and non-stationary physiological time series. PMID:28539889

Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

PubMed

Ramchandra, Rohit; Hood, Sally G; May, Clive N

2014-08-01

Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN. Copyright © 2014 the American Physiological Society.

Chronic Interactions Between Carotid Baroreceptors and Chemoreceptors in Obesity Hypertension.

PubMed

Lohmeier, Thomas E; Iliescu, Radu; Tudorancea, Ionut; Cazan, Radu; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

2016-07-01

Carotid bodies play a critical role in protecting against hypoxemia, and their activation increases sympathetic activity, arterial pressure, and ventilation, responses opposed by acute stimulation of the baroreflex. Although chemoreceptor hypersensitivity is associated with sympathetically mediated hypertension, the mechanisms involved and their significance in the pathogenesis of hypertension remain unclear. We investigated the chronic interactions of these reflexes in dogs with sympathetically mediated, obesity-induced hypertension based on the hypothesis that hypoxemia and tonic activation of carotid chemoreceptors may be associated with obesity. After 5 weeks on a high-fat diet, the animals experienced a 35% to 40% weight gain and increases in arterial pressure from 106±3 to 123±3 mm Hg and respiratory rate from 8±1 to 12±1 breaths/min along with hypoxemia (arterial partial pressure of oxygen=81±3 mm Hg) but eucapnia. During 7 days of carotid baroreflex activation by electric stimulation of the carotid sinus, tachypnea was attenuated, and hypertension was abolished before these variables returned to prestimulation values during a recovery period. After subsequent denervation of the carotid sinus region, respiratory rate decreased transiently in association with further sustained reductions in arterial partial pressure of oxygen (to 65±2 mm Hg) and substantial hypercapnia. Moreover, the severity of hypertension was attenuated from 125±2 to 116±3 mm Hg (45%-50% reduction). These findings suggest that hypoxemia may account for sustained stimulation of peripheral chemoreceptors in obesity and that this activation leads to compensatory increases in ventilation and central sympathetic outflow that contributes to neurogenically mediated hypertension. Furthermore, the excitatory effects of chemoreceptor hyperactivity are abolished by chronic activation of the carotid baroreflex. © 2016 American Heart Association, Inc.

Using the morphology of photoplethysmogram peaks to detect changes in posture.

PubMed

Linder, Stephen P; Wendelken, Suzanne M; Wei, Edward; McGrath, Susan P

2006-06-01

The morphology of the pulsatile component of the photoplethysmogram (PPG) has been shown to vary with physiology, but changes in the morphology caused by the baroreflex response to orthostatic stress have not been investigated. Using two FDA approved Nonin pulse oximeters placed on the finger and ear, we monitored 11 subjects, for three trials each, as they stood from a supine position. Each cardiac cycle was automatically extracted from the PPG waveform and characterized using statistics corresponding to normalized peak width, instantaneous heart rate, and amplitude of the pulsatile component of the ear PPG. A nonparametric Wilcoxon rank sum test was then used to detect in real-time changes in these features with p < 0.01. In all 33 trials, the standing event was detected as an abrupt change in at least two of these features, with only one false alarm. In 26 trials, an abrupt change was detected in all three features, with no false alarms. An increase in the normalize peak width was detected before an increase in heart rate, and in 21 trials a peak in the feature was detected before or as standing commenced. During standing, the pulse rate always increases, and then amplitude of the ear PPG constricts by a factor of two or more. We hypothesis that the baroreflex first reduces the percentage of time blood flow is stagnant during the cardiac cycle, then increases the hear rate, and finally vasoconstricts the peripheral tissue in order to reestablishing a nominal blood pressure. These three features therefore can be used as a detector of the baroreflex response to changes in posture or other forms of blood volume sequestration.

PTEN, a negative regulator of PI3K/Akt signaling, sustains brain stem cardiovascular regulation during mevinphos intoxication.

PubMed

Tsai, Ching-Yi; Wu, Jacqueline C C; Fang, Chi; Chang, Alice Y W

2017-09-01

Activation of PI3K/Akt signaling, leading to upregulation of nitric oxide synthase II (NOS II)/peroxynitrite cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins cardiovascular depression induced by the organophosphate pesticide mevinphos. By exhibiting dual-specificity protein- and lipid-phosphatase activity, phosphatase and tensin homolog (PTEN) directly antagonizes the PI3K/Akt signaling by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate, the lipid product of PI3K. Based on the guiding hypothesis that PTEN may sustain brain stem cardiovascular regulation during mevinphos intoxication as a negative regulator of PI3K/Akt signaling in the RVLM, we aimed in this study to clarify the mechanistic role of PTEN in mevinphos-induced circulatory depression. Microinjection bilaterally of mevinphos (10 nmol) into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension and a decrease in baroreflex-mediated sympathetic vasomotor tone. There was progressive augmentation in PTEN activity as reflected by a decrease in the oxidized form of PTEN in the RVLM during mevinhpos intoxication, without significant changes in the mRNA or protein level of PTEN. Loss-of-function manipulations of PTEN in the RVLM by immunoneutralization, pharmacological blockade or siRNA pretreatment significantly potentiated the increase in Akt activity or NOS II/peroxynitrite cascade in the RVLM, enhanced the elicited hypotension and exacerbated the already reduced baroreflex-mediated sympathetic vasomotor tone. We conclude that augmented PTEN activity via a decrease of its oxidized form in the RVLM sustains brain stem cardiovascular regulation during mevinphos intoxication via downregulation of the NOS II/peroxynitrite cascade as a negative regulator of PI3K/Akt signaling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of PI3K/Akt signaling in rostral ventrolateral medulla impairs brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication.

PubMed

Tsai, Ching-Yi; Chang, Alice Y W; Chan, Julie Y H; Chan, Samuel H H

2014-03-01

As the most widely used pesticides in the globe, the organophosphate compounds are understandably linked with the highest incidence of suicidal poisoning. Whereas the elicited toxicity is often associated with circulatory depression, the underlying mechanisms require further delineation. Employing the pesticide mevinphos as our experimental tool, we evaluated the hypothesis that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-κB on activation of the PI3K/Akt cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins the circulatory depressive effects of organophosphate poisons. Microinjection of mevinphos (10 nmol) bilaterally into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension that was accompanied sequentially by an increase (Phase I) and a decrease (Phase II) of an experimental index for the baroreflex-mediated sympathetic vasomotor tone. There were also progressive augmentations in PI3K or Akt enzyme activity and phosphorylation of p85 or Akt(Thr308) subunit in the RVLM that were causally related to an increase in NF-κB transcription activity and elevation in NOS II or peroxynitrite expression. Loss-of-function manipulations of PI3K or Akt in the RVLM significantly antagonized the reduced baroreflex-mediated sympathetic vasomotor tone and hypotension during Phase II mevinphos intoxication, and blunted the increase in NF-κB/NOS II/peroxynitrite signaling. We conclude that activation of the PI3K/Akt cascade, leading to upregulation of NF-κB/NOS II/peroxynitrite signaling in the RVLM, elicits impairment of brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication. Copyright © 2014 Elsevier Inc. All rights reserved.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.

PubMed

Subha, M; Pal, Pravati; Pal, G K; Habeebullah, S; Adithan, C; Sridhar, M G

Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (β = 0.276, P = 0.020), TNF-α (β = 0.408, P = 0.002), interferon-γ (β = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (β = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Costa, F.; Furlan, R.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1999-01-01

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Involvement of Type 1 Angiontensin II Receptor (AT1) in Cardiovascular Changes Induced by Chronic Emotional Stress: Comparison between Homotypic and Heterotypic Stressors.

PubMed

Costa-Ferreira, Willian; Vieira, Jonas O; Almeida, Jeferson; Gomes-de-Souza, Lucas; Crestani, Carlos C

2016-01-01

Consistent evidence has shown an important role of emotional stress in pathogenesis of cardiovascular diseases. Additionally, studies in animal models have demonstrated that daily exposure to different stressor (heterotypic stressor) evokes more severe changes than those resulting from repeated exposure to the same aversive stimulus (homotypic stressor), possibly due to the habituation process upon repeated exposure to the same stressor. Despite these pieces of evidence, the mechanisms involved in the stress-evoked cardiovascular dysfunction are poorly understood. Therefore, the present study investigated the involvement of angiotensin II (Ang II) acting on the type 1 Ang II receptor (AT1) in the cardiovascular dysfunctions evoked by both homotypic and heterotypic chronic emotional stresses in rats. For this purpose, we compared the effect of the chronic treatment with the AT1 receptor antagonist losartan (30 mg/kg/day, p.o.) on the cardiovascular and autonomic changes evoked by the heterotypic stressor chronic variable stress (CVS) and the homotypic stressor repeated restraint stress (RRS). RRS increased the sympathetic tone to the heart and decreased the cardiac parasympathetic activity, whereas CVS decreased the cardiac parasympathetic activity. Additionally, both stressors impaired the baroreflex function. Alterations in the autonomic activity and the baroreflex impairment were inhibited by losartan treatment. Additionally, CVS reduced the body weight and increased the circulating corticosterone; however, these effects were not affected by losartan. In conclusion, these findings indicate the involvement of angiotensin II/AT1 receptors in the autonomic changes evoked by both homotypic and heterotypic chronic stressors. Moreover, the present results provide evidence that the increase in the circulating corticosterone and body weight reduction evoked by heterotypic stressors are independent of AT1 receptors.

Physiological basis for human autonomic rhythms

NASA Technical Reports Server (NTRS)

Eckberg, D. L.

2000-01-01

Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a measurement that identifies functional reflex abnormalities contributing to terminal dysrhythmias.

Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats.

PubMed

Flanagan, Evelyn T; Buckley, Maria M; Aherne, Claire M; Lainis, Fredolin; Sattar, Munavvar; Johns, Edward J

2008-09-01

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P<0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P<0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P<0/05), while the mid-point blood pressure was lower, by 15% (P<0/05), and the range of the curve was 60% (P<0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P<0.05) in the untreated rats but had no effect in the isoprenaline-caffeine- or the thyroxine-treated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high- and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.

Nitric oxide-dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle

PubMed Central

Chavoshan, Bahman; Sander, Mikael; Sybert, Troy E; Hansen, Jim; Victor, Ronald G; Thomas, Gail D

2002-01-01

Nitric oxide (NO) attenuates α-adrenergic vasoconstriction in contracting rodent skeletal muscle, but it is unclear if NO plays a similar role in human muscle. We therefore hypothesized that in humans, NO produced in exercising skeletal muscle blunts the vasoconstrictor response to sympathetic activation. We assessed vasoconstrictor responses in the microcirculation of human forearm muscle using near-infrared spectroscopy to measure decreases in muscle oxygenation during reflex sympathetic activation evoked by lower body negative pressure (LBNP). Experiments were performed before and after NO synthase inhibition produced by systemic infusion of NG-nitro-l-arginine methyl ester (l-NAME). Before l-NAME, LBNP at −20 mmHg decreased muscle oxygenation by 20 ± 2 % in resting forearm and by 2 ± 3 % in exercising forearm (n = 20), demonstrating metabolic modulation of sympathetic vasoconstriction. As expected, l-NAME increased mean arterial pressure by 17 ± 3 mmHg, leading to baroreflex-mediated supression of baseline muscle sympathetic nerve activity (SNA). The increment in muscle SNA in response to LBNP at −20 mmHg also was attenuated after l-NAME (before, +14 ± 2; after, +8 ± 1 bursts min−1; n = 6), but this effect of l-NAME was counteracted by increasing LBNP to −40 mmHg (+19 ± 2 bursts min−1). After l-NAME, LBNP at −20 mmHg decreased muscle oxygenation similarly in resting (−11 ± 3 %) and exercising (−10 ± 2 %) forearm (n = 12). Likewise, LBNP at −40 mmHg decreased muscle oxygenation both in resting (−19 ± 4 %) and exercising (−21 ± 5 %) forearm (n = 8). These data advance the hypothesis that NO plays an important role in modulating sympathetic vasoconstriction in the microcirculation of exercising muscle, because such modulation is abrogated by NO synthase inhibition with l-NAME. PMID:11927694

Intermittent noise stress causes baroreflex desensitization and decreased heart rate variability in Wistar Kyoto rats exposed to ozone

EPA Science Inventory

This study shows that intermittent noise stress worsens the cardiopulmonary response of rats to ozone. It increases electrical disturbances and causes dysfunction the homeostatic regulation of the heart and vasculature. Although the acute cardiovascular health impacts o...

[Burnout syndrome: a "true" cardiovascular risk factor].

PubMed

Cursoux, Pauline; Lehucher-Michel, Marie-Pascale; Marchetti, Hélène; Chaumet, Guillaume; Delliaux, Stéphane

2012-11-01

The burnout syndrome is characterized by emotional exhaustion, depersonalization and reduced personal accomplishment in individuals professionally involved with others. The burnout syndrome is poorly recognized, particularly in France, as a distinct nosology from adaptation troubles, stress, depression, or anxiety. Several tools quantifying burnout and emotional exhaustion exist, the most spread is the questionnaire called Maslach Burnout Inventory. The burnout syndrome alters cardiovascular function and its neuroregulation by autonomic nervous system and is associated with: increased sympathetic tone to heart and vessels after mental stress, lowered physiological post-stress vagal rebound to heart, and lowered arterial baroreflex sensitivity. Job strain as burnout syndrome seems to be a real independent cardiovascular risk factor. Oppositely, training to manage emotions could increase vagal tone to heart and should be cardio-protective. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Postural Regulation of Muscle Sympathetic Nerve Activity Before and After Simulated and Actual Microgravity Deconditioning

NASA Technical Reports Server (NTRS)

Pawelczyk, J. A.; Levine, B. D.

1999-01-01

The etiology of orthostatic intolerance after spaceflight is multifaceted. Morphological adaptations, in particular cardiac atrophy, are likely to magnify the decrease in stroke volume that occurs with reductions in cardiac filling pressure when standing. Neural adaptations may be inferred as well, as reductions in carotid-cardiac baroreflex responsiveness have been reported following bedrest deconditioning and spaceflight. Neural control of vascular resistance has not been studied directly when orthostatic intolerance is florid in the hours following spaceflight. However, the increases in systemic vascular resistance and plasma catecholamines during orthostatic stress are inappropriately low in orthostatically intolerant subjects following spaceflight, suggesting that deficits in the regulation of vascular resistance may be associated with hypoadrenergic function. The studies described in this abstract were designed to test this hypothesis.

A single exposure to acrolein desensitizes baroreflex responsiveness and increases cardiac arrhythmias in normotensive and hypertensive rats

EPA Science Inventory

Background – Short-term exposure to air pollutants has been linked to acute cardiovascular morbidity and mortality. Even in the absence of overt symptoms, pollutants can cause subtle disruptions of internal regulatory mechanisms, which maintain homeostatic balance, thereby reduci...

Reduced cardiac vagal activity in obese children and adolescents.

PubMed

Dangardt, Frida; Volkmann, Reinhard; Chen, Yun; Osika, Walter; Mårild, Staffan; Friberg, Peter

2011-03-01

  Obese children present with various cardiovascular risk factors affecting their future health. In adults, cardiac autonomic function is a major risk factor, predicting cardiovascular morbidity and mortality. We hypothesized that obese children and adolescents had a lower cardiac vagal activity than lean subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS), reflecting the dynamic regulation of cardiac vagal function, in large groups of obese and lean young individuals.   Cardiac BRS, using the sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls) and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared to both overweight and lean subjects [16±7 versus 21±9 (P<0·01) and 22±10 ms per mmHg (P<0·0001), respectively]. The differences remained after correcting for age, gender and pubertal status.   Children with obesity had low vagal activity at rest, and there was no gender difference. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Spaceflight alters autonomic regulation of arterial pressure in humans

NASA Technical Reports Server (NTRS)

Fritsch-Yelle, Janice M.; Charles, John B.; Jones, Michele M.; Beightol, Larry A.; Eckberg, Dwain L.

1994-01-01

Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4 - 5 days) impairs one neutral mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8 - 14 days. We found the following changes between preflight and landing day: (1) orthostatic tolerance decreased; (2) R-R interval spectral power in the 0.05- to 0.15-Hz band increased; (3) plasma norepinephrine and epinephrine levels increased; (4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and (5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevent reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.

Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats.

PubMed

Loria, Analia S; Osborn, Jeffrey L

2017-07-01

Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal α-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, α 1 -adrenergic receptors (α 1 -ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the α-AR subtype gene expression was determined by RT-PCR. Renal cortical α 1 -AR density was similar between MatSep and control tissues (B max = 44 ± 1 vs. 42 ± 2 fmol/mg protein, respectively); however, MatSep reduced α 1 -AR density in renal vasculature (B max = 47 ± 4 vs. 62 ± 4 fmol/mg protein, P < 0.05, respectively). In a separate group of rats, the pressor, bradycardic, and renal vascular constrictor responses to acute norepinephrine injection (NE, 0.03-0.25 μg/μl) were determined under anesthesia. Attenuated NE-induced renal vasoconstriction was observed in rats exposed to MatSep compared with control ( P < 0.05). A third group of rats was infused at steady state with the α 1 agonist phenylephrine (10 μg/min iv) and vasodilator sodium nitroprusside (5 μg/min iv). The difference between the change in heart rate/mean arterial pressure slopes was indicative of reduced baroreflex sensitivity in MatSep vs. control rats (-0.45 ± 0.04 vs. -0.95 ± 0.07 beats·min -1 ·mmHg -1 , P < 0.05). These data support the notion that reduced α-adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone. Copyright © 2017 the American Physiological Society.

Baroreflex Sensitivity Is Reduced in Adolescents with Probable Developmental Coordination Disorder

ERIC Educational Resources Information Center

Coverdale, Nicole S.; O'Leary, Deborah D.; Faught, Brent E.; Chirico, Daniele; Hay, John; Cairney, John

2012-01-01

Developmental coordination disorder (DCD) is a neurodevelopmental condition characterized by poor motor skills leading to a significant impairment in activities of daily living. Compared to typically developing children, those with DCD are less fit and physically active, and have increased body fat. This is an important consequence as both…

NASA/ASEE Summer Faculty Fellowship Program

NASA Technical Reports Server (NTRS)

Hosler, E. Ramon (Editor); Armstrong, Dennis W. (Editor)

1989-01-01

The contractor's report contains all sixteen final reports prepared by the participants in the 1989 Summer Faculty Fellowship Program. Reports describe research projects on a number of different topics. Interface software, metal corrosion, rocket triggering lightning, automatic drawing, 60-Hertz power, carotid-cardiac baroreflex, acoustic fields, robotics, AI, CAD/CAE, cryogenics, titanium, and flow measurement are discussed.

System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade

NASA Technical Reports Server (NTRS)

Mullen, T. J.; Appel, M. L.; Mukkamala, R.; Mathias, J. M.; Cohen, R. J.

1997-01-01

We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

[The cardiovagal, cardiosympathetic and vasosympathetic arterial baroreflexes and the neural control of short-term blood pressure].

PubMed

Robles-Cabrera, Adriana; Michel-Chávez, Anaclara; Callejas-Rojas, Rodolfo C; Malamud-Kessler, Caroline; Delgado, Guillermo; Estañol-Vidal, Bruno

2014-12-01

The factors that control the blood pressure are punctually regulated to keep it in reference values. These are maintained through autoregulatory mechanisms, humoral, nervous and endothelial-related. The humoral mechanisms are complex and modify the long-term blood pressure, in the other hand, the neurogenic mechanisms, are reflexive and can be observed in beat-to-beat changes of blood pressure. The nervous cardiovascular reflexes are mediated by high-pressure and low-pressure baroreceptors, as cardiovagal, cardiosympathetic and vasosympathetic. The arterial baroreceptor are stimulated when the blood volume-ejected by the ventricle distend the arterial walls. The neural discharge travels to the autonomic centers in the brain stem and the result is the modification of the heart rate and the vascular smooth muscle tone. This sudden modification is the responsible of the beat-to-beat (short-term) blood pressure variability. A review was made on the history of the physiology and experiments of the cardiovagal, cardiosympathetic and vasosympathetic baroreflexes and its influence in the short-term blood pressure variability.

Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

PubMed

Ronchi, Silas Nascimento; Brasil, Girlandia Alexandre; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Scherer, Rodrigo; Costa, Helber B; Romão, Wanderson; Boëchat, Giovanna Assis Pereira; Lenz, Dominik; Fronza, Marcio; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

2015-10-01

The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting antihypertensive agent. © The Author(s), 2015.

Endurance training in mild hypertension - effects on ambulatory blood pressure and neural circulatory control.

PubMed

Narkiewicz; Somers

1997-10-01

This review examines the effects of a single bout of exercise and of endurance training on blood pressure in patients with hypertension. Possible autonomic mechanisms that mediate these changes in blood pressure are reviewed briefly. Blood pressure rises during exercise. During the second half hour after exercise blood pressure is lower. This p;ost-exercise reduction in blood pressure is associated with a decrease in muscle sympathetic nerve activity, an increase in baroreflex gain and a reduction in the level of blood pressure (set point) at which baroreflex activation occurs. The post-exercise fall in blood pressure appears to be limited to several hours and is not likely to explain any chronic reduction in blood pressure from endurance training. Endurance training elicits modest (approximately 4-5 mmHg) reductions in blood pressure. Because of the intrinsic variability of blood pressure, the decreases in blood pressure after endurance training is evident, especially when multiple measurements of blood pressure are obtained. Studies using 24 h blood pressure measurements suggest that, although endurance training lowers daytime blood pressure, blood pressure during sleep remains unchanged. The mechanism underlying the reduction in blood pressure in endurance training is not known. Although physical fitness is known to attenuate the sympathetic response to acute exercise, whether resting sympathetic drive is decreased with endurance training remains controversial. The slowing of heart rate that accompanies endurance training is also associated with an increase in variability of heart rate. The slower heart rate, increased variability of heart rate and lower blood pressure after endurance training are accompanied by an increase in baroreflex sensitivity. Even though the antihypertensive effect of endurance training is modest, the favourable effects of physical fitness on other risk factors for cardiovascular disease make exercise training an important approach in the management of hypertensive patients, particularly for sedentary patients with borderline and mild hypertension.

An Innovative Technique to Assess Spontaneous Baroreflex Sensitivity with Short Data Segments: Multiple Trigonometric Regressive Spectral Analysis.

PubMed

Li, Kai; Rüdiger, Heinz; Haase, Rocco; Ziemssen, Tjalf

2018-01-01

Objective: As the multiple trigonometric regressive spectral (MTRS) analysis is extraordinary in its ability to analyze short local data segments down to 12 s, we wanted to evaluate the impact of the data segment settings by applying the technique of MTRS analysis for baroreflex sensitivity (BRS) estimation using a standardized data pool. Methods: Spectral and baroreflex analyses were performed on the EuroBaVar dataset (42 recordings, including lying and standing positions). For this analysis, the technique of MTRS was used. We used different global and local data segment lengths, and chose the global data segments from different positions. Three global data segments of 1 and 2 min and three local data segments of 12, 20, and 30 s were used in MTRS analysis for BRS. Results: All the BRS-values calculated on the three global data segments were highly correlated, both in the supine and standing positions; the different global data segments provided similar BRS estimations. When using different local data segments, all the BRS-values were also highly correlated. However, in the supine position, using short local data segments of 12 s overestimated BRS compared with those using 20 and 30 s. In the standing position, the BRS estimations using different local data segments were comparable. There was no proportional bias for the comparisons between different BRS estimations. Conclusion: We demonstrate that BRS estimation by the MTRS technique is stable when using different global data segments, and MTRS is extraordinary in its ability to evaluate BRS in even short local data segments (20 and 30 s). Because of the non-stationary character of most biosignals, the MTRS technique would be preferable for BRS analysis especially in conditions when only short stationary data segments are available or when dynamic changes of BRS should be monitored.

Discharges of aortic and carotid sinus baroreceptors during spontaneous motor activity and pharmacologically evoked pressor interventions.

PubMed

Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

2014-07-01

Our laboratory has demonstrated that the cardiomotor component of aortic baroreflex is temporarily inhibited at the onset of spontaneous motor activity in decerebrate cats, without altering carotid sinus baroreflex. A reason for this dissociation may be attributed to a difference in the responses between aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity. The stimulus-response curves of AoNA and CsNA against mean arterial blood pressure (MAP) were compared between the pressor interventions evoked by spontaneous motor activity and by intravenous administration of phenylephrine or norepinephrine, in which the responses in heart rate (HR) were opposite (i.e., tachycardia vs. baroreflex bradycardia), despite the identical increase in MAP of 34-40 mmHg. In parallel to the pressor response, mean AoNA and CsNA increased similarly by 78-81 and by 88 % of the baseline control, respectively, irrespective of whether the pressor response was evoked by spontaneous motor activity or by a pharmacological intervention. The slope of the stimulus-response curve of the mean AoNA became greater (P < 0.05) during spontaneous motor activity as compared to the pharmacological intervention. On the other hand, the stimulus-response curve of the mean CsNA and its slope were equal (P > 0.05) between the two pressor interventions. Furthermore, the slopes of the stimulus-response curves of both diastolic AoNA and CsNA (defined as the minimal value within a beat) exhibited a greater increase during spontaneous motor activity. All differences in the slopes of the stimulus-response curves were abolished by restraining HR at the intrinsic cardiac frequency. In conclusion, mean mass activities of both aortic and carotid sinus baroreceptors are able to encode the beat-by-beat changes in MAP not only at rest but also during spontaneous motor activity and spontaneous motor activity-related reduction of aortic baroreceptor activity is denied accordingly.

Assessment of the dynamic interactions between heart rate and arterial pressure by the cross time-frequency analysis.

PubMed

Orini, M; Laguna, P; Mainardi, L T; Bailón, R

2012-03-01

In this study, a framework for the characterization of the dynamic interactions between RR variability (RRV) and systolic arterial pressure variability (SAPV) is proposed. The methodology accounts for the intrinsic non-stationarity of the cardiovascular system and includes the assessment of both the strength and the prevalent direction of local coupling. The smoothed pseudo-Wigner-Ville distribution (SPWVD) is used to estimate the time-frequency (TF) power, coherence, and phase-difference spectra with fine TF resolution. The interactions between the signals are quantified by time-varying indices, including the local coupling, phase differences, time delay, and baroreflex sensitivity (BRS). Every index is extracted from a specific TF region, localized by combining information from the different spectra. In 14 healthy subjects, a head-up tilt provoked an abrupt decrease in the cardiovascular coupling; a rapid change in the phase difference (from 0.37 ± 0.23 to -0.27 ± 0.22 rad) and time delay (from 0.26 ± 0.14 to -0.16 ± 0.16 s) in the high-frequency band; and a decrease in the BRS (from 23.72 ± 7.66 to 6.92 ± 2.51 ms mmHg(-1)). In the low-frequency range, during a head-up tilt, restoration of the baseline level of cardiovascular coupling took about 2 min and SAPV preceded RRV by about 0.85 s during the whole test. The analysis of the Eurobavar data set, which includes subjects with intact as well as impaired baroreflex, showed that the presented methodology represents an improved TF generalization of traditional time-invariant methodologies and can reveal dysfunctions in subjects with baroreflex impairment. Additionally, the results also suggest the use of non-stationary signal-processing techniques to analyze signals recorded under conditions that are usually supposed to be stationary.

Mechanisms of insulin action on sympathetic nerve activity

NASA Technical Reports Server (NTRS)

Muntzel, Martin S.; Anderson, Erling A.; Johnson, Alan Kim; Mark, Allyn L.

1996-01-01

Insulin resistance and hyperinsulinemia may contribute to the development of arterial hypertension. Although insulin may elevate arterial pressure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation during insulin may be mediated by the baroreflex, or by modulation of norepinephrine release from sympathetic nerve endings, it has been shown repeatedly that insulin increases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Recent experiments from our laboratory involving direct measurements of regional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administration of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Interestingly, this pattern of regional sympathetic nerve responses to central neural administration of insulin is similar to that seen with systemic administration of insulin. Further, lesions of the anteroventral third ventricle hypothalamic (AV3V) region abolished increases in sympathetic activity to systemic administration of insulin with euglycemic clamp, suggesting that AV3V-related structures are critical for insulin-induced elevations in sympathetic outflow.

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality.

PubMed

Jorge, Luciana; Rodrigues, Bruno; Rosa, Kaleizu Teodoro; Malfitano, Christiane; Loureiro, Tatiana Carolina Alba; Medeiros, Alessandra; Curi, Rui; Brum, Patricia Chakur; Lacchini, Silvia; Montano, Nicola; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2011-04-01

To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

Teaching Baroreflex Physiology to Medical Students: A Comparison of Quiz-Based and Conventional Teaching Strategies in a Laboratory Exercise

ERIC Educational Resources Information Center

Berg, Ronan M. G.; Plovsing, Ronni R.; Damgaard, Morten

2012-01-01

Quiz-based and collaborative teaching strategies have previously been found to be efficient for the improving meaningful learning of physiology during lectures. These approaches have, however, not been investigated during laboratory exercises. In the present study, we compared the impact of solving quizzes individually and in groups with…

Evaluation of Baroreflex Effectiveness Index during Real and Simulated Microgravity: Relation to Orthostatic Intolerance

NASA Technical Reports Server (NTRS)

Moore, Rachel; Stenger, Michael; Platts, Steven; Lee, Stuart

2013-01-01

Bed Rest and Space Flight cause a significant decrease in BEI. BR causes similar changes to BEI as SF. BEI may not correlate with subjects experiencing presyncope, but error is high and n is low. Compression Garments have the potential to restore BEI after short duration BR, but do not prevent recovery.

Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Engelke, K. A.; Doerr, D. F.

1999-01-01

Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP.

PubMed

Irnaten, M; Neff, R A; Wang, J; Loewy, A D; Mettenleiter, T C; Mendelowitz, D

2001-01-01

A fluorescent transneuronal marker capable of labeling individual neurons in a central network while maintaining their normal physiology would permit functional studies of neurons within entire networks responsible for complex behaviors such as cardiorespiratory reflexes. The Bartha strain of pseudorabies virus (PRV), an attenuated swine alpha herpesvirus, can be used as a transsynaptic marker of neural circuits. Bartha PRV invades neuronal networks in the CNS through peripherally projecting axons, replicates in these parent neurons, and then travels transsynaptically to continue labeling the second- and higher-order neurons in a time-dependent manner. A Bartha PRV mutant that expresses green fluorescent protein (GFP) was used to visualize and record from neurons that determine the vagal motor outflow to the heart. Here we show that Bartha PRV-GFP-labeled neurons retain their normal electrophysiological properties and that the labeled baroreflex pathways that control heart rate are unaltered by the virus. This novel transynaptic virus permits in vitro studies of identified neurons within functionally defined neuronal systems including networks that mediate cardiovascular and respiratory function and interactions. We also demonstrate superior laryngeal motorneurons fire spontaneously and synapse on cardiac vagal neurons in the nucleus ambiguus. This cardiorespiratory pathway provides a neural basis of respiratory sinus arrhythmias.

High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia

PubMed Central

Grisé, Kenneth N.; Olver, T. Dylan; McDonald, Matthew W.; Dey, Adwitia; Jiang, Mao; Lacefield, James C.; Shoemaker, J. Kevin; Noble, Earl G.; Melling, C. W. James

2016-01-01

Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9–17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM. PMID:26885531

Opioid innervation of the caudal ventrolateral medulla is not critical for the expression of the aortic depressor nerve response in the rabbit.

PubMed

Drolet, G; Morilak, D A; Chalmers, J

1991-01-01

We investigated the influence of endogenous opioids in the caudal ventrolateral medulla (CVLM) on the expression of the baroreflex response induced by the electrical stimulation (50 Hz, 0.2 ms, 11 V, 10 s) of the aortic depressor nerve. We used microinjection of selective opioid antagonists into the functionally identified depressor area of the CVLM in chloralose-anesthetized rabbits. Injection of vehicles or the mu-antagonist beta-funaltrexamine (0.3 nmol) into the CVLM had no effects, while naloxone (20 nmol), ICI 174,864 (delta-antagonist, 0.3 nmol) or nor-binaltorphimine (kappa-antagonist, 1 nmol) abolished the depressor response, but themselves all elicited a tonic depressor effect as well. In contrast, intravenous naloxone (5 mg/kg) induced a small but significant increase in arterial pressure and did not alter the depressor response. Hypotensive hemorrhage induced a decrease in arterial pressure similar to that seen with local injection of naloxone into the CVLM, but did not change the reflex, suggesting that the reflex abolition was not due to the decrease in basal arterial pressure per se. CVLM injection of glutamate (10 nmol) or the GABA-antagonist bicuculline (0.1 nmol), non-opioid agents which activate CVLM and induce a tonic depressor effect, also abolished the depressor response suggesting that the reflex abolition was secondary to general activation or disinhibition of the CVLM. Thus, although the CVLM is tonically inhibited by endogenous opioid inputs acting via delta- and kappa-receptors, our data provide no evidence that opioid neurons which provide input to this region constitute a specific and integral component in mediating the aortic depressor response. However, the more general role that opioids play in tonically influencing the resting level of activity in the CVLM, is nevertheless very important in enabling the normal expression of this baroreflex.

Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function.

PubMed

Liu, Yang; Wu, Di; Qu, Mei-Yu; He, Jian-Li; Yuan, Mei; Zhao, Miao; Wang, Jian-Xin; He, Jian; Wang, Lu-Qi; Guo, Xin-Jing; Zuo, Meng; Zhao, Shu-Yang; Ma, Mei-Na; Li, Jun-Nan; Shou, Weinian; Qiao, Guo-Fen; Li, Bai-Yan

2016-10-04

Molecular and cellular mechanisms of neuropeptide-Y (NPY)-mediated gender-difference in blood pressure (BP) regulation are largely unknown. Baroreceptor sensitivity (BRS) was evaluated by measuring the response of BP to phenylephrine/nitroprusside. Serum NPY concentration was determined using ELISA. The mRNA and protein expression of NPY receptors were assessed in tissue and single-cell by RT-PCR, immunoblot, and immunohistochemistry. NPY was injected into the nodose while arterial pressure was monitored. Electrophysiological recordings were performed on nodose neurons from rats by patch-clamp technique. The BRS was higher in female than male and ovariectomized rats, while serum NPY concentration was similar among groups. The sex-difference was detected in Y1R, not Y2R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y1R and Y2R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y1R expression/distribution was identical between A- and C-types, whereas, expressed level of Y2R was ~15 and ~7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y1R in nodose elevated BP, while activation of Y2R did the opposite. Activation of Y1R did not alter action potential duration (APD) of A-types, but activation of Y2R- and Y1R/Y2R in Ah- and C-types frequency-dependently prolonged APD. N-type ICa was reduced in A-, Ah- and C-types when either Y1R, Y2R, or both were activated. The sex-difference in Y1R expression was also observed in NTS. Sex- and afferent-specific expression of Neuropeptide-Y receptors in baroreflex afferent pathway may contribute to sexual-dimorphic neurocontrol of BP regulation.

The nature of the autonomic dysfunction in multiple system atrophy

NASA Technical Reports Server (NTRS)

Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

2002-01-01

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder.

PubMed

Park, Jeanie; Marvar, Paul J; Liao, Peizhou; Kankam, Melanie L; Norrholm, Seth D; Downey, Ryan M; McCullough, S Ashley; Le, Ngoc-Anh; Rothbaum, Barbara O

2017-07-15

Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known. Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients. Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation. Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients. Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD.  Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress:  combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2 ± 1.0 vs. +1.2 ± 1.3 bursts min -1 , P < 0.001) and heart rate responses (+3.2 ± 1.1 vs. -2.3 ± 1.0 beats min -1 , P = 0.003) were significantly augmented during VRCE.  Similarly, in PTSD vs. Controls, MSNA (+21.0 ± 2.6 vs. +6.7 ± 1.5 bursts min -1 , P < 0.001) and diastolic BP responses (+6.3 ± 1.0 vs. +3.5 ± 1.0 mmHg, P = 0.011) were significantly augmented during MA but not during CPT (P = not significant). In the PTSD group, sympathetic BRS (-1.2 ± 0.2 vs. -2.0 ± 0.3 burst incidence mmHg -1 , P = 0.026) and cardiovagal BRS (9.5 ± 1.4 vs. 23.6 ± 4.3 ms mmHg -1 , P = 0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1 ± 0.4 vs. 1.0 ± 0.3 mg L -1 , P = 0.047). Augmented SNS and haemodynamic responses to mental stress, blunted BRS and inflammation may contribute to an increased CV risk in PTSD. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Current Treatments in Familial Dysautonomia

PubMed Central

Palma, Jose-Alberto; Kaufmann, Lucy; Fuente, Cristina; Percival, Leila; Mendoza, Carlos; Kaufmann, Horacio

2014-01-01

Introduction Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (type III). The disease is caused by a point mutation in the IKBKAP gene that affects the splicing of the elongator-1 protein (also known as IKAP). Patients have dramatic blood pressure instability due to baroreflex failure, chronic kidney disease, and impaired swallowing leading to recurrent aspiration pneumonia, which results in chronic lung disease. Diminished pain and temperature perception results in neuropathic joints and thermal injuries. Impaired proprioception leads to gait ataxia. Optic neuropathy and corneal opacities lead to progressive visual loss. Areas covered This article reviews current therapeutic strategies for the symptomatic treatment of FD, as well as the potential of new gene modifying agents. Expert opinion Therapeutic focus on FD is centered on reducing the catecholamine surges caused by baroreflex failure. Managing neurogenic dysphagia with effective protection of the airway passages and prompt treatment of aspiration pneumonias is necessary to prevent respiratory failure. Sedative medications should be used cautiously due to risk of respiratory depression. Non-invasive ventilation during sleep effectively manages apneas and prevents hypercapnia. Clinical trials of compounds that increase levels of IKAP (ELP-1) are underway and will determine whether they can reverse or slow disease progression. PMID:25323828

Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Shea, J. D.; Doerr, D. F.; Convertino, V. A.

1992-01-01

To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid-cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg).

Altered baroreflex control of forearm vascular resistance during simulated microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Doerr, D. F.; Vernikos, J.

1994-01-01

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

Baroreflex sensitivity in children and adolescents: physiology, hypertension, obesity, diabetes mellitus.

PubMed

Honzíková, N; Závodná, E

2016-12-13

The increased prevalence of obesity in children and its complications have led to a greater interest in studying baroreflex sensitivity (BRS) in children. This review of BRS in children and adolescents includes subtopics on: 1. Resting values of BRS and their reproducibility, 2. Genetics of BRS, 3. The role of a primarily low BRS and obesity in the development of hypertension, and 4. Association of diabetes mellitus, BRS, and obesity. The conclusions specific to this age follow from this review: 1. The mean heart rate (HR) influences the measurement of BRS. Since the mean HR decreases during adolescence, HR should be taken into account. 2. A genetic dependency of BRS was found. 3. Low BRS values may precede pathological blood-pressure elevation in children with white-coat hypertension. We hypothesize that low BRS plays an active role in the emergence of hypertension in youth. A contribution of obesity to the development of hypertension was also found. We hypothesize that both factors, a primarily low BRS and obesity, are partially independent risk factors for hypertension in youths. 4. In diabetics, a low BRS compared to healthy children can be associated with insulin resistance. A reversibility of the BRS values could be possible after weight loss.

Heart rate turbulence.

PubMed

Cygankiewicz, Iwona

2013-01-01

Heart rate turbulence (HRT) is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats. Heart rate turbulence is quantified by: turbulence onset (TO) reflecting the initial acceleration of heart rate following premature beat and turbulence slope (TS) describing subsequent deceleration of heart rate. Abnormal HRT identifies patients with autonomic dysfunction or impaired baroreflex sensitivity due to variety of disorders, but also may reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy. More importantly, impaired HRT has been shown to identify patients at high risk of all-cause mortality and sudden death, particularly in postinfarction and congestive heart failure patients. It should be emphasized that abnormal HRT has a well-established role in stratification of postinfarction and heart failure patients with relatively preserved left ventricular ejection fraction. The ongoing clinical trials will document whether HRT can be used to guide implantation of cardioverter-defibrillators in this subset of patients, not covered yet by ICD guidelines. This review focuses on the current state-of-the-art knowledge regarding clinical significance of HRT in detection of autonomic dysfunction and regarding the prognostic significance of this parameter in predicting all-cause mortality and sudden death. © 2013.

Orthostatic Hypotension: Mechanisms, Causes, Management

PubMed Central

Tomalia, Victoria A.

2015-01-01

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson's disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH. PMID:26174784

Neurohumoral Mechanisms Associated with Orthostasis: Reaffirmation of the Significant Contribution of the Heart Rate Response

DTIC Science & Technology

2014-06-30

baroreceptor stimu- lation (i.e., lower arterial blood pressure ) suggests an association between a depressed baroreflex response and development of...orthostatic tolerance, blood pressure regulation, lower body negative pressure , parasympathetic activity, sympathetic activity, propranolol, atropine...body negative pressure (LBNP) so that comparisons of physiology in individuals with high and low tolerance to central hypovolemia could be studied at

The treatment with pyridostigmine improves the cardiocirculatory function in rats with chronic heart failure.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; de Melo, Rubens Fernando; Fazan, Rubens; Salgado, Helio C

2013-01-01

Sympathetic hyperactivity and its outcome in heart failure have been thoroughly investigated to determine the focus of pharmacologic approaches targeting the sympathetic nervous system in the treatment of this pathophysiological condition. On the other hand, therapeutic approaches aiming to protect the reduced cardiac parasympathetic function have not received much attention. The present study evaluated rats with chronic heart failure (six to seven weeks after coronary artery ligation) and the effects of an increased parasympathetic function by pyridostigmine (an acetylcholinesterase inhibitor) on the following aspects: arterial pressure (AP), heart rate (HR), baroreceptor and Bezold-Jarisch reflex, pulse interval (PI) and AP variability, cardiac sympathetic and parasympathetic tonus, intrinsic heart rate (i-HR) and cardiac function. Conscious rats with heart failure exhibited no change in HR, Bezold-Jarisch reflex, PI variability and cardiac sympathetic tonus. On the other hand, these animals presented hypotension and reduced baroreflex sensitivity, power in the low frequency (LF) band of the systolic AP spectrum, cardiac parasympathetic tonus and i-HR, while anesthetized rats exhibited reduced cardiac performance. Pyridostigmine prevented the attenuation of all the parameters examined, except basal AP and cardiac performance. In conclusion, the blockade of acetylcholinesterase with pyridostigmine was revealed to be an important pharmacological approach, which could be used to increase parasympathetic function and to improve a number of cardiocirculatory parameters in rats with heart failure. Copyright © 2012 Elsevier B.V. All rights reserved.

Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction.

PubMed

Rodrigues, Bruno; Jorge, Luciana; Mostarda, Cristiano T; Rosa, Kaleizu T; Medeiros, Alessandra; Malfitano, Christiane; de Souza, Alcione L; Viegas, Katia Aparecida da Silva; Lacchini, Silvia; Curi, Rui; Brum, Patricia C; De Angelis, Kátia; Irigoyen, Maria Cláudia

2012-09-01

Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca(2+) handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca(2+) handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI. Copyright © 2012 Elsevier Inc. All rights reserved.

Rightward dominance in temporal high-frequency electrical asymmetry corresponds to higher resting heart rate and lower baroreflex sensitivity in a heterogeneous population.

PubMed

Tegeler, Charles H; Shaltout, Hossam A; Tegeler, Catherine L; Gerdes, Lee; Lee, Sung W

2015-06-01

Explore potential use of a temporal lobe electrical asymmetry score to discriminate between sympathetic and parasympathetic tendencies in autonomic cardiovascular regulation. 131 individuals (82 women, mean age 43.1, range 13-83) with diverse clinical conditions completed inventories for depressive (CES-D or BDI-II) and insomnia-related (ISI) symptomatology, and underwent five-minute recordings of heart rate and blood pressure, allowing calculation of heart rate variability and baroreflex sensitivity (BRS), followed by one-minute, two-channel, eyes-closed scalp recordings of brain electrical activity. A temporal lobe high-frequency (23-36 Hz) electrical asymmetry score was calculated for each subject by subtracting the average amplitude in the left temporal region from amplitude in the right temporal region, and dividing by the lesser of the two. Depressive and insomnia-related symptomatology exceeding clinical threshold levels were reported by 48% and 50% of subjects, respectively. Using a cutoff value of 5% or greater to define temporal high-frequency asymmetry, subjects with leftward compared to rightward asymmetry were more likely to report use of a sedative-hypnotic medication (42% vs. 22%, P = 0.02). Among subjects with asymmetry of 5% or greater to 30% or greater, those with rightward compared to leftward temporal high-frequency asymmetry had higher resting heart rate (≥5% asymmetry, 72.3 vs. 63.8, P = 0.004; ≥10%, 71.5 vs. 63.0, P = 0.01; ≥20%, 72.2 vs. 64.2, P = 0.05; ≥30%, 71.4 vs. 64.6, P = 0.05). Subjects with larger degrees of rightward compared to leftward temporal high-frequency asymmetry had lower baroreflex sensitivity (≥40% asymmetry, 10.6 vs. 16.4, P = 0.03; ≥50% asymmetry, 10.4 vs. 16.7, P = 0.05). In a heterogeneous population, individuals with rightward compared to leftward temporal high-frequency electrical asymmetry had higher resting heart rate and lower BRS. Two-channel recording of brain electrical activity from bilateral temporal regions appears to hold promise for further investigation as a means to assess cortical activity associated with autonomic cardiovascular regulation.

CCISS, Vascular and BP Reg: Canadian space life science research on ISS

NASA Astrophysics Data System (ADS)

Hughson, Richard L.; Shoemaker, J. Kevin; Arbeille, Philippe

2014-11-01

A comprehensive goal of the Canadian Space Agency studies (CCISS, Vascular and BP Reg) has been to investigate the efficacy of current exercise countermeasures to maintain cardiovascular and cerebrovascular health on return to Earth after up to 6-months in space. Results from the CCISS experiments revealed no significant change of in-flight heart rate during daily activities or sleep, and small, but variable between astronauts, post-flight elevation. The between astronaut differences were exaggerated during measurement of spontaneous baroreflex slope, which was reduced post-flight (P<0.05) during paced breathing with 3 astronauts having significant correlations between reduced baroreflex and reduced RR-interval (consistent with reduced fitness). Cerebrovascular autoregulation and CO2 response were mildly impaired after flight. Some loss of in-flight fitness of astronauts in Vascular was reflected by the increase in HR at a work rate of 161±46 W of 12.3±10.5 bpm, 10.4±5.9 bpm and 13.4±5.7 bpm for early-flight, late-flight and R+1, respectively. On return to gravity, changes in resting heart rate for supine (5.9±3.5 bpm), sit (8.1±3.3 bpm) and stand (10.3±10.0 bpm) were small but variable between individuals (from -5 bpm to +20 bpm in post-flight standing) and not related to the change in exercise heart rate. In Vascular astronauts, pulse wave transit time measured to the finger tended to be reduced post-flight and carotid artery distensibility was significantly reduced (P=0.03, and n=6). The heart rate and baroreflex data suggest that some astronauts return with cardiovascular deconditioning in spite of the exercise regimes. However, greater arterial stiffness is common among all astronauts studied to date. The new CSA project, BP Reg, will monitor inflight blood pressure in an attempt to identify astronauts in greater need for countermeasures. Future research should focus on whether Vascular changes in astronauts might make them an appropriate model to study the mechanisms of arterial aging on Earth.

Autonomic control of ultradian and circadian rhythms of blood pressure, heart rate, and baroreflex sensitivity in spontaneously hypertensive rats.

PubMed

Oosting, J; Struijker-Boudier, H A; Janssen, B J

1997-04-01

To examine the influence of the autonomic nervous system on ultradian and circadian rhythms of blood pressure, heart rate and baroreflex sensitivity of heart rate (BRS) in spontaneously hypertensive rats (SHR). Spontaneous fluctuations in blood pressure, heart rate and BRS in SHR were recorded continuously for 24 h using a computerized system and compared with those in Wistar-Kyoto (WKY) rats. Furthermore, 24 h recordings were performed in SHR during cardiac autonomic blockade by metoprolol and methyl-atropine, vascular autonomic blockade by prazosin, ganglionic blockade by hexamethonium and vagal stimulation by a low dose of scopolamine. The magnitudes of the ultradian fluctuations in blood pressure, heart rate and BRS were assessed by wide-band spectral analysis techniques. The BRS was lower in SHR than it was in WKY rats throughout the 24 h cycle. In both strains high values were found during the light, resting period, whereas low values were found during the first hours of the dark, active period. The circadian rhythmicity of the blood pressure in SHR was abolished completely during the infusions of prazosin and hexamethonium. In contrast, the circadian rhythmicities of the blood pressure and heart rate were not altered by infusions of metoprolol, methyl-atropine and the low dose of scopolamine. Power spectra of the blood pressure and heart rate lacked predominant peaks at ultradian frequencies and showed 1/f characteristics. In the absence of autonomic tone, the ultradian fluctuations in heart rate, but not in blood pressure, were decreased. The ultradian BRS spectra had no 1/f shape, but showed a major peak at approximately equal to 20 min for 71% of the WKY rats and 42% of the SHR. The influence of the autonomic nervous system on the blood pressure and heart rats in SHR is frequency-dependent. The circadian, but not ultradian, blood pressure rhythmicity is controlled by vascular autonomic activity. Conversely, the circadian, but not ultradian, heart rate rhythmicity is independent of autonomic tone. In rats, just as in humans, the trough in baroreflex sensitivity occurred after the sleeping period, when locomotor activity is resumed.

Daily inspiratory muscle training lowers blood pressure and vascular resistance in healthy men and women.

PubMed

DeLucia, Claire M; De Asis, Roxanne M; Bailey, E Fiona

2018-02-01

What is the central question of this study? What impact does inspiratory muscle training have on systemic vascular resistance, cardiac output and baroreflex sensitivity in adult men and women? What is the main finding and its importance? Inspiratory muscle training exerts favorable effects on blood pressure, vascular resistance and perception of stress. This exercise format is well-tolerated and equally effective whether implemented in men or women. Previous work has shown that inspiratory muscle training (IMT) lowers blood pressure after a mere 6 weeks, identifying IMT as a potential therapeutic intervention to prevent or treat hypertension. Here, we explore the effects of IMT on respiratory muscle strength and select cardiovascular parameters in recreationally active men and women. Subjects were randomly assigned to IMT (n = 12, 75% maximal inspiratory pressure) or sham training (n = 13, 15% maximal inspiratory pressure) groups and underwent a 6-week intervention comprising 30 breaths day -1 , 5 days week -1 . Pre- and post-training measures included maximal inspiratory pressure and resting measures of blood pressure, cardiac output, heart rate, spontaneous cardiac baroreflex sensitivity and systemic vascular resistance. We evaluated psychological and sleep status via administration of the Cohen-Hoberman inventory of physical symptoms and the Epworth sleepiness scale. Male and female subjects in the IMT group showed declines in systolic/diastolic blood pressures (-4.3/-3.9 mmHg, P < 0.025) and systemic vascular resistance (-3.5 mmHg min l -1 , P = 0.008) at week 6. There was no effect of IMT on cardiac output (P = 0.722), heart rate (P = 0.795) or spontaneous cardiac baroreflex sensitivity (P = 0.776). The IMT subjects also reported fewer stress-related symptoms (pre- versus post-training, 12.5 ± 8.5 versus 7.2 ± 9.7, P = 0.025). Based on these results, we suggest that a short course of IMT confers significant respiratory and cardiovascular improvements and parallel (modest) psychological benefits in healthy men and women. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Intracardiac Origin of Heart Rate Variability, Pacemaker Funny Current and their Possible Association with Critical Illness

PubMed Central

Papaioannou, Vasilios E; Verkerk, Arie O; Amin, Ahmed S; de Bakker, Jaques MT

2013-01-01

Heart rate variability (HRV) is an indirect estimator of autonomic modulation of heart rate and is considered a risk marker in critical illness, particularly in heart failure and severe sepsis. A reduced HRV has been found in critically ill patients and has been associated with neuro-autonomic uncoupling or decreased baroreflex sensitivity. However, results from human and animal experimental studies indicate that intracardiac mechanisms might also be responsible for interbeat fluctuations. These studies have demonstrated that different membrane channel proteins and especially the so-called ‘funny’ current (If), an hyperpolarization-activated, inward current that drives diastolic depolarization resulting in spontaneous activity in cardiac pacemaker cells, are altered during critical illness. Furthermore, membrane channels kinetics seem to have significant impact upon HRV, whose early decrease might reflect a cellular metabolic stress. In this review article we present research findings regarding intracardiac origin of HRV, at the cellular level and in both isolated sinoatrial node and whole ex vivo heart preparations. In addition, we will review results from various experimental studies that support the interrelation between If and HRV during endotoxemia. We suggest that reduced HRV during sepsis could also be associated with altered pacemaker cell membrane properties, due to ionic current remodeling. PMID:22920474

Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales.

PubMed

Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto

2017-08-01

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains. NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV. Copyright © 2017 the American Physiological Society.

One night on-call: sleep deprivation affects cardiac autonomic control and inflammation in physicians.

PubMed

Tobaldini, Eleonora; Cogliati, Chiara; Fiorelli, Elisa M; Nunziata, Vanessa; Wu, Maddalena A; Prado, Marta; Bevilacqua, Maurizio; Trabattoni, Daria; Porta, Alberto; Montano, Nicola

2013-10-01

Sleep loss is associated with increased cardiovascular morbidity and mortality. It is known that chronic sleep restriction affects autonomic cardiovascular control and inflammatory response. However, scanty data are available on the effects of acute sleep deprivation (ASD) due to night shifts on the cardiovascular system and its capability to respond to stressor stimuli. The aim of our study was to investigate whether a real life model of ASD, such as "one night on-call", might alter the autonomic dynamic response to orthostatic challenge and modify the immune response in young physicians. Fifteen healthy residents in Internal Medicine were studied before and after one night on-call at Rest and during a gravitational stimulus (head up-tilt test, HUT). Heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were analyzed during Rest and HUT before and after ASD. Plasmatic hormones (epinephrine, norepinephrine, cortisol, renin, aldosterone, ACTH) and tissue inflammatory cytokines were measured at baseline and after ASD. HRV analysis revealed a predominant sympathetic modulation and a parasympathetic withdrawal after ASD. During HUT, the sympathovagal balance shifted towards a sympathetic predominance before and after ASD. However, the magnitude of the autonomic response was lower after ASD. BPV and BRS remained unchanged before and after ASD as the hormone levels, while IFN-γ increased after ASD compared to baseline. In summary, one night of sleep deprivation, at least in this real-life model, seems to affect cardiovascular autonomic response and immune modulation, independently by the activation of the hypothalamic-pituitary axis. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Inspiratory Resistance as a Potential Treatment for Orthostatic Intolerance and Hemorrhagic Shock

DTIC Science & Technology

2005-04-01

central blood volume by forcing the thoracic muscles to develop increased negative pressure , thus drawing venous blood from extrathoracic cavi- ties...cardiac baroreflex sensitivity associated with re- ductions of central blood volume during lower body negative pressure (LBNP) are reversed with...9:621–26. 8. Chapleau MW, Abboud FM. Contrasting effects of static and pulsatile pressure on carotid baroreceptor activity in dogs. Circ Res 1987; 61

The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

NASA Technical Reports Server (NTRS)

Ray, Chester A.; Monahan, Kevin D.

2002-01-01

1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

L-NAME, a nitric oxide synthase inhibitor, as a potential countermeasure to post-suspension hypotension in rats

NASA Technical Reports Server (NTRS)

Bayorh, M. A.; Socci, R. R.; Watts, S.; Wang, M.; Eatman, D.; Emmett, N.; Thierry-Palmer, M.

2001-01-01

A large number of astronauts returning from spaceflight experience orthostatic hypotension. This hypotension may be due to overproduction of vasodilatory mediators, such as nitric oxide (NO) and prostaglandins. To evaluate the role of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we assessed the cardiovascular responses and vascular reactivity to 7-day 30 degrees tail-suspension and a subsequent 6 hr post-suspension period in conscious rats. After a pre-suspension reading, direct MAP and heart rate (HR) were measured daily and every 2 hrs post-suspension. The NO synthase inhibitor L-NAME (20 mg/kg, i.v.), or saline, were administered after the 7th day reading prior to release from suspension and at 2 and 4 hrs post-suspension. At 6 hrs post-suspension, vascular reactivity was assessed. While MAP did not change during the suspension period, it was reduced post-suspension. Heart rate was not significantly altered. L-NAME administration reversed the post-suspension reduction in MAP. In addition, the baroreflex sensitivity for heart rate was modified by L-NAME. Thus, the post-suspension reduction in MAP may be due to overproduction of NO and altered baroreflex activity.

Limits of clinical tests to screen autonomic function in diabetes type 1.

PubMed

Ducher, M; Bertram, D; Sagnol, I; Cerutti, C; Thivolet, C; Fauvel, J P

2001-11-01

A precocious detection of cardiac autonomic dysfunction is of major clinical interest that could lead to a more intensive supervision of diabetic patients. However, classical clinical exploration of cardiac autonomic function is not easy to undertake in a reproducible way. Thus, respective interests of autonomic nervous parameters provided by both clinical tests and computerized analysis of resting blood pressure were checked in type 1 diabetic patients without orthostatic hypotension and microalbuminuria. Thirteen diabetic subjects matched for age and gender to thirteen healthy subjects volunteered to participate to the study. From clinical tests (standing up, deep breathing, Valsalva maneuver, handgrip test), autonomic function was scored according to Ewing's methodology. Analysis of resting beat to beat blood pressure provided autonomic indices of the cardiac function (spectral analysis or Z analysis). 5 of the 13 diabetic patients exhibited a pathological score (more than one pathological response) suggesting the presence of cardiovascular autonomic dysfunction. The most discriminative test was the deep breathing test. However, spectral indices of BP recordings and baro-reflex sensitivity (BRS) of these 5 subjects were similar to those of healthy subjects and of remaining diabetic subjects. Alteration in Ewing's score given by clinical tests may not reflect an alteration of cardiac autonomic function in asymptomatic type 1 diabetic patients, because spectral indices of sympathetic and parasympathetic (including BRS) function were within normal range. Our results strongly suggest to confront results provided by both methodologies before concluding to an autonomic cardiac impairment in asymptomatic diabetic patients.

Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure: does ejection fraction matter?

PubMed

Andrade, David C; Arce-Alvarez, Alexis; Toledo, Camilo; Díaz, Hugo S; Lucero, Claudia; Quintanilla, Rodrigo A; Schultz, Harold D; Marcus, Noah J; Amann, Markus; Del Rio, Rodrigo

2018-03-01

Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.

Impact of augmenting dialysis frequency and duration on cardiovascular function.

PubMed

Ly, Joseph; Chan, Christopher T

2006-01-01

Conventional hemodialysis (CHD) only delivers 10% to 15% of renal function in a nonphysiological intermittent mode. Because it occurs nightly and is sustained over a longer dialysis time, the uremic clearance provided by nocturnal hemodialysis (NHD) far exceeds that of CHD. Increasing the dose and frequency of dialysis by NHD has been demonstrated, in both short- and long-term studies, to reverse several important risk factors for adverse cardiovascular events in patients with end-stage renal disease such as hypertension, left ventricular hypertrophy, systolic dysfunction, conduit artery stiffness, attenuated baroreflex regulation of heart rate, disturbed heart rate variability, sleep apnea, and endothelium-dependent vasodilation. In addition, the Toronto NHD experience has reported an emerging body of evidence demonstrating the benefits of NHD on anemia management, inflammation, and endothelial progenitor cell biology. The mechanism(s) by which nocturnal hemodialysis improves cardiovascular outcomes are under active investigation by our group. It is tempting to speculate that NHD has the potential to decrease endothelial/myocardial injury and restore simultaneously endothelial repair, thereby improving cardiovascular function in patients with end-stage renal disease. The objectives of the present document are (1) to review the mechanisms underlying dialysis-associated cardiovascular morbidity and (2) to describe the restorative potential of NHD on the cardiovascular system.

Individual Differences in the Temporal Profile of Cardiovascular Responses to Head Down Tilt and Orthostatic Stress with and Without Fluid Loading

NASA Technical Reports Server (NTRS)

Cowings, Patricia; Toscano, William; Kanis, Dionisios; Gebreyesus, Fiyore

2013-01-01

Susceptibility of healthy astronauts to orthostatic hypotension and presyncope is exacerbated upon return from spaceflight. Hypo-volemia is suspected to play an important role in cardiovascular deconditioning following exposure to spaceflight, which may lead to increased peripheral resistance, attenuated arterial baroreflex, and changes in cardiac function. The effect of altered gravity during space flight and planetary transition on human cardiovascular function is of critical importance to maintenance of astronaut health and safety. A promising countermeasure for post-flight orthostatic intolerance is fluid loading used to restore loss fluid volume by giving crew salt tablets and water prior to re-entry. Eight men and eight women will be tested during two, 6-hour exposures to 6o HDT: 1) fluid loading, 2) no fluid loading. Before and immediately after each HDT, subjects will perform a stand test to assess their orthostatic tolerance. Physiological measures (e.g., ECG, blood pressure, peripheral blood volume) will be continuously monitored while echocardiography measures are recorded at 30-minute intervals during HDT and stand tests. Preliminary results (N=4) clearly show individual differences in responses to this countermeasure and the time course of physiological changes induced by HDT.

Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM-HF Trial.

PubMed

Nearing, Bruce D; Libbus, Imad; Amurthur, Badri; Kenknight, Bruce H; Verrier, Richard L

2016-09-01

Chronic vagus nerve stimulation (VNS) applied to produce biomimetic levels of parasympathetic activation is feasible, well tolerated, safe, improves left ventricular ejection fraction, NYHA class, heart rate variability, and baroreflex function, and reduces T-wave alternans (TWA) in patients with chronic heart failure. However, the acute effects of VNS on beat-to-beat heart rate dynamics have not been systematically characterized in humans. We evaluated acute effects of VNS on R-R-interval dynamics during the VNS titration period in patients (n = 59) enrolled in ANTHEM-HF trial by quantifying effects during continuous cyclic VNS (14-seconds on-time, 66-seconds off-time) adjusted to the maximum tolerable dose without excessive (<4 bpm) bradycardia during the 10-week titration period. VNS elicited an immediate change in heart rate that was correlated to VNS current amplitude, pulse width, and frequency. Heart rate decreased more in the 28 patients with right-sided stimulation (-2.22 ± 0.13 bpm) than in the 31 patients with left-sided stimulation (-0.60 ± 0.08 bpm, P < 0.001). The linear correlation between stimulus intensity and lengthening of the R-R interval was stronger among the 28 patients with right-sided VNS implantation (r = 0.88, P < 0.0001) than among the 31 patients with left-sided VNS implantation (r = 0.49, P < 0.002). In all patients, the heart rate change elicited by VNS was significantly greater than the change during the same timing intervals in 10 randomly selected patients without stimulation (+0.08 ± 0.06 bpm, P < 0.001). Instantaneous heart rate change during therapeutic levels of VNS in patients with heart failure indicates consistent modulation of the autonomic nervous system for both left- and right-sided stimulation. © 2016 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.

Arterial Pulse Pressure and Its Association With Reduced Stroke Volume During Progressive Central Hypovolemia

DTIC Science & Technology

2006-09-01

NM, Joyner MJ. Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans. Am J Physiol Heart Circ Physiol...Arterial Pulse Pressure and Its Association With Reduced Stroke Volume During Progressive Central Hypovolemia Victor A. Convertino, PhD, William H...reduction of SV and change in MSNA during graded central hypovolemia in humans. Methods: After a 12-minute baseline data collection period, 13 men were

Cortical regions associated with orthostatic stress in conscious humans

NASA Astrophysics Data System (ADS)

Kimmerly, Derek S.; O'Leary, Debbie D.; Cechetto, Angela; Shoemaker, Kevin J.

2005-08-01

The purpose of this study was to determine the cortical structures associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging (fMRI). Heart rate (HR) and LBNP were simultaneously monitored during scanning. Central venous pressure (CVP), muscle sympathetic nerve activity (MSNA) and arterial blood pressure (ABP) were measured on a separate day. Random effects analyses (SPM2) were used to evaluate fMRI signal changes that correlated separately with both LBNP and HR (15 and 35-mmHg versus 5-mmHg LBNP). LBNP at 15- and 35-mmHg decreased CVP and increased MSNA, both P < 0.05 versus baseline) but only LBNP at 35- mmHg elevated HR. ABP was similar at all levels of LBNP . Cortical regions demonstrating increased activity at higher HR and greater LBNP included the right superior posterior insula and the cerebellum. Conversely, bilateral anterior insular cortices, the right anterior cingulate, amygdala, and mediodorsal nucleus of the thalamus showed decreased neural activation.

Fine structure of the low-frequency spectra of heart rate and blood pressure

PubMed Central

Kuusela, Tom A; Kaila, Timo J; Kähönen, Mika

2003-01-01

Background The aim of this study was to explore the principal frequency components of the heart rate and blood pressure variability in the low frequency (LF) and very low frequency (VLF) band. The spectral composition of the R–R interval (RRI) and systolic arterial blood pressure (SAP) in the frequency range below 0.15 Hz were carefully analyzed using three different spectral methods: Fast Fourier transform (FFT), Wigner-Ville distribution (WVD), and autoregression (AR). All spectral methods were used to create time–frequency plots to uncover the principal spectral components that are least dependent on time. The accurate frequencies of these components were calculated from the pole decomposition of the AR spectral density after determining the optimal model order – the most crucial factor when using this method – with the help of FFT and WVD methods. Results Spectral analysis of the RRI and SAP of 12 healthy subjects revealed that there are always at least three spectral components below 0.15 Hz. The three principal frequency components are 0.026 ± 0.003 (mean ± SD) Hz, 0.076 ± 0.012 Hz, and 0.117 ± 0.016 Hz. These principal components vary only slightly over time. FFT-based coherence and phase-function analysis suggests that the second and third components are related to the baroreflex control of blood pressure, since the phase difference between SAP and RRI was negative and almost constant, whereas the origin of the first component is different since no clear SAP–RRI phase relationship was found. Conclusion The above data indicate that spontaneous fluctuations in heart rate and blood pressure within the standard low-frequency range of 0.04–0.15 Hz typically occur at two frequency components rather than only at one as widely believed, and these components are not harmonically related. This new observation in humans can help explain divergent results in the literature concerning spontaneous low-frequency oscillations. It also raises methodological and computational questions regarding the usability and validity of the low-frequency spectral band when estimating sympathetic activity and baroreflex gain. PMID:14552660

Fine structure of the low-frequency spectra of heart rate and blood pressure.

PubMed

Kuusela, Tom A; Kaila, Timo J; Kähönen, Mika

2003-10-13

The aim of this study was to explore the principal frequency components of the heart rate and blood pressure variability in the low frequency (LF) and very low frequency (VLF) band. The spectral composition of the R-R interval (RRI) and systolic arterial blood pressure (SAP) in the frequency range below 0.15 Hz were carefully analyzed using three different spectral methods: Fast Fourier transform (FFT), Wigner-Ville distribution (WVD), and autoregression (AR). All spectral methods were used to create time-frequency plots to uncover the principal spectral components that are least dependent on time. The accurate frequencies of these components were calculated from the pole decomposition of the AR spectral density after determining the optimal model order--the most crucial factor when using this method--with the help of FFT and WVD methods. Spectral analysis of the RRI and SAP of 12 healthy subjects revealed that there are always at least three spectral components below 0.15 Hz. The three principal frequency components are 0.026 +/- 0.003 (mean +/- SD) Hz, 0.076 +/- 0.012 Hz, and 0.117 +/- 0.016 Hz. These principal components vary only slightly over time. FFT-based coherence and phase-function analysis suggests that the second and third components are related to the baroreflex control of blood pressure, since the phase difference between SAP and RRI was negative and almost constant, whereas the origin of the first component is different since no clear SAP-RRI phase relationship was found. The above data indicate that spontaneous fluctuations in heart rate and blood pressure within the standard low-frequency range of 0.04-0.15 Hz typically occur at two frequency components rather than only at one as widely believed, and these components are not harmonically related. This new observation in humans can help explain divergent results in the literature concerning spontaneous low-frequency oscillations. It also raises methodological and computational questions regarding the usability and validity of the low-frequency spectral band when estimating sympathetic activity and baroreflex gain.

Hypovolemic intolerance to lower body negative pressure in female runners.

PubMed

Morikawa, T; Sagawa, S; Torii, R; Endo, Y; Yamazaki, F; Shiraki, K

2001-12-01

An attenuated baroreflex response and orthostatic intolerance have been reported in endurance-trained male athletes; however, it is still unknown whether this occurs also in females. The purpose of the present study was to examine whether endurance exercise-trained women had a predisposition to orthostatic compromise, and if so, what causative factor(s) may induce orthostatic intolerance. We studied cardiovascular and hormonal responses to graded lower body negative pressure (LBNP) (0 to -60 mm Hg) in 26 middle-distance female runners (18.6 +/- 0.1 yr) as the exercise-trained (ET) subjects and 23 age-matched untrained (UT) control subjects. On the basis of the occurrence of syncope episodes during LBNP, ET and UT subjects were further allocated to two groups; ET with presyncope (ET+syncope) and without presyncope (ET-syncope) and UT with presyncope (UT+syncope) and without presyncope (UT-syncope). Occurrence of presyncope episodes during LBNP was higher in ET (65.4%, P < 0.05) than that for UT (34.8%). Leg compliance was higher (P < 0.05) in ET than in UT. LBNP reduced stroke volume (SV) more (P < 0.05), increased heart rate (HR) higher (P < 0.05), and increased forearm vascular resistance (FVR) more in ET+syncope as compared with the other groups. Response of vasoactive hormones to LBNP was higher in ET+syncope (P < 0.05) than that of the other groups except for norepinephrine (NE); high in both ET+syncope and UT+syncope. The relationship between SV and NE, an index of sympathetic neuronal response, had no training-related changes during LBNP. We conclude that exercise-trained females have a high incidence of orthostatic intolerance during LBNP, with a greater reduction of SV independent of changes in baroreflex and neurohumoral function. A lower incidence of LBNP intolerance in UT may be accounted for by a lower reduction of SV during LBNP. An increase in leg compliance in the exercise-trained females may play an important role in inducing pronounced reduction of SV and hence the intolerance to LBNP.

A-7E Software Module Guide.

DTIC Science & Technology

1981-12-08

o 14 A& B:2.1 Function Driver Module.. ..... .... 14’ ’: B:2.2 Shared Services Module . . . o o . 0 -15 M’ 5:3 Software Decision Module...2.1.13 Weapon Release Functions... ........24 C:2.l.14 Ground Test Functions .. ........... 24 C:2.2 Shared Services Module Decomposition. ........24 C...Driver (FD) Module supported by a Shared Services (SS) Module. B:2.1 FUNCTION DRIVER MODULE The Function Driver Module consists of a set of individual

Chewing-induced hypertension in afferent baroreflex failure: a sympathetic response?

PubMed

Fuente Mora, Cristina; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto; Kaufmann, Horacio

2015-11-01

What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P < 0.0001) and additional signs of sympathetic activation, including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic activation. The increase in blood pressure is exaggerated in patients with FD as a result of blunted afferent baroreceptor signalling. The chewing pressor response may be useful as a counter-manoeuvre to raise blood pressure and prevent symptomatic orthostatic hypotension in patients with FD. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Left Ventricular, Systemic Arterial and Baroreflex Responses to Ketamine and TEE in Chronically Instrumented Monkeys

DTIC Science & Technology

2001-12-01

instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to...isoflurane in 100% oxy- gen) prior to insertion of the high -fidelity pressure micromanome- ters during cardiac fluoroscopy. Once the micromanometer trans...and allowed to fully recover from the isoflurane seda- tion for a period of 60 min, during which blood pressure and aortic flow were monitored to ensure

Strength Training Does Not Affect Vagal-cardiac Control or Cardiovagal Baroreflex Sensitivity in Young Healthy Subjects

DTIC Science & Technology

2005-03-01

shown to help control or lower arterial blood pressure (Carter JR et al. 2003; Kelley and Kelley 2000), and has been recommended as therapy for...as determined by a physician during a routine physical examination. The experimental protocol was approved by the Human Research Committee of Michigan...car diovagal and sympathetic responses to Valsalva’s maneuver. Med Sci Sports Exerc 34:928 935 Ekblom B, Kilbom ASA, Soltysiak J (1973) Physical

Effects of inspiratory impedance on the carotid-cardiac baroreflex response in humans.

DTIC Science & Technology

2004-08-01

seems con- traindicated, it is similar to the concurrent elevation in HR and arterial blood pressure responses observed dur- ing physical exercise.Two...expect withdrawal of vagal activity and no significant change in sympathetic activity with heart rate below 100 bpm during physical exercise [31]. To... quadriplegics . Am J Physiol Regulatory Integrative Comp Physiol 260: R576–R580 7. Convertino VA, Doerr DF, Eckberg DL, Fritsch JM, Vernikos-Danellis J

Effects of acute hyperthermia on the carotid baroreflex control of heart rate in humans

NASA Astrophysics Data System (ADS)

Yamazaki, F.; Sagawa, S.; Torii, R.; Endo, Y.; Shiraki, K.

The purpose of this study was to examine the effect of hyperthermia on the carotid baroreceptor-cardiac reflexes in humans. Nine healthy males underwent acute hyperthermia (esophageal temperature 38.0° C) produced by hot water-perfused suits. Beat-to-beat heart rate (HR) responses were determined during positive and negative R-wave-triggered neck pressure steps from +40 to -65 mm Hg during normothermia and hyperthermia. The carotid baroreceptor-cardiac reflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure. Buffering capacity of the HR response to carotid distending pressure was evaluated in % from a reference point calculated as (HR at 0 mm Hg neck pressure-minimum HR)/HR range ×100. An upward shift of the curve was evident in hyperthermia because HR increased from 57.7+/-2.4 beats/min in normothermia to 88.7+/-4.1 beats/min in hyperthermia (P<0.05) without changes in mean arterial pressure. The maximum slope of the curve in hyperthermia was similar to that in normothermia. The reference point was increased (P<0.05) during hyperthermia. These results suggest that the sensitivity of the carotid baroreflex of HR remains unchanged in hyperthermia. However, the capacity for tachycardia response to rapid onset of hypotension is reduced and the capacity for bradycardia response to sudden hypertension is increased during acute hyperthermia.

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by 0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.

Application of acute maximal exercise to protect orthostatic tolerance after simulated microgravity

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Doerr, D. F.; Crandall, C. G.; Convertino, V. A.

1996-01-01

We tested the hypothesis that one bout of maximal exercise performed at the conclusion of prolonged simulated microgravity would improve blood pressure stability during an orthostatic challenge. Heart rate (HR), mean arterial blood pressure (MAP), norepinephrine (NE), epinephrine (E), arginine vasopressin (AVP), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cardiac output (Q), forearm vascular resistance (FVR), and changes in leg volume were measured during lower body negative pressure (LBNP) to presyncope in seven subjects immediately prior to reambulation from 16 days of 6 degrees head-down tilt (HDT) under two experimental conditions: 1) after maximal supine cycle ergometry performed 24 h before returning to the upright posture (exercise) and 2) without exercise (control). After HDT, the reduction of LBNP tolerance time from pre-HDT levels was greater (P = 0.041) in the control condition (-2.0 +/- 0.2 min) compared with the exercise condition (-0.4 +/- 0.2 min). At presyncope after HDT, FVR and NE were higher (P < 0.05) after exercise compared with control, whereas MAP, HR, E, AVP, PRA, ANP, and leg volume were similar in both conditions. Plasma volume (PV) and carotid-cardiac baroreflex sensitivity were reduced after control HDT, but were restored by the exercise treatment. Maintenance of orthostatic tolerance by application of acute intense exercise after 16 days of simulated microgravity was associated with greater circulating levels of NE, vasoconstriction, Q, baroreflex sensitivity, and PV.

Heart rate turbulence parameters correlate with post-premature ventricular contraction changes in muscle sympathetic activity.

PubMed

Segerson, Nathan M; Wasmund, Stephen L; Abedin, Moeen; Pai, Rakesh K; Daccarett, Marcos; Akoum, Nazem; Wall, T Scott; Klein, Richard C; Freedman, Roger A; Hamdan, Mohamed H

2007-03-01

Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.

Assessing the strength of cardiac and sympathetic baroreflex controls via transfer entropy during orthostatic challenge

NASA Astrophysics Data System (ADS)

Porta, Alberto; Marchi, Andrea; Bari, Vlasta; De Maria, Beatrice; Esler, Murray; Lambert, Elisabeth; Baumert, Mathias

2017-05-01

The study assesses the strength of the causal relation along baroreflex (BR) in humans during an incremental postural challenge soliciting the BR. Both cardiac BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA). A model-based transfer entropy method was applied to quantify the strength of the coupling from SAP to HP and from DAP to MSNA. The confounding influences of respiration were accounted for. Twelve young healthy subjects (20-36 years, nine females) were sequentially tilted at 0°, 20°, 30° and 40°. We found that (i) the strength of the causal relation along the cBR increases with tilt table inclination, while that along the sBR is unrelated to it; (ii) the strength of the causal coupling is unrelated to the gain of the relation; (iii) transfer entropy indexes are significantly and positively associated with simplified causality indexes derived from BR sequence analysis. The study proves that causality indexes are complementary to traditional characterization of the BR and suggests that simple markers derived from BR sequence analysis might be fruitfully exploited to estimate causality along the BR. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Low dose of methyltestosterone in ovariectomised rats improves baroreflex sensitivity without geno- and cytotoxicity.

PubMed

Terra, Denise G; de Lima, Ewelyne M; do Nascimento, Andrews M; Brasil, Girlandia A; Filete, Placielle F; Kalil, Ieda C; Lenz, Dominik; Endringer, Denise C; Bissoli, Nazaré S; de Andrade, Tadeu U

2016-08-01

This study evaluated the effects of the isolated use of a low dose of methyltestosterone (MT) on cardiovascular reflexes and hormonal levels and its geno- and cytotoxic safety in ovariectomized rats. Female Wistar rats were divided into four groups (n = 6), respectively: SHAM (received vehicle methylcellulose 0.5%), SHAM + MT (received MT 0.05 mg/kg), OVX (received vehicle), and OVX + MT (received MT). Twenty-one days after ovariectomy, treatment was given orally daily for 28 days. The Bezold-Jarisch reflex (BJR) was analyzed by measuring the bradycardic and hypotensive responses elicited by phenylbiguanide (PBG) administration. The baroreflex sensitivity (BRS) was evaluated by phenylephrine and sodium nitroprussite. Myocyte hypertrophy was determined by morphometric analysis of H&E stained slides. Biochemical data were analyzed, as well as micronucleus assay. MT improved BRS and increased testosterone values, but did not change estradiol in the OVX group. MT did not promote changes in mean arterial pressure, heart rate, BJR, serum concentrations of troponin I, weight and histopathology of the heart. MT was able to restore the BRS in OVX rats. The geno- and cytotoxic safety of the MT was demonstrated by the absence of an increase in the micronucleus (PCEMN) or change in the ratio between normochromatic erythrocytes and polychromatic erythrocytes (NCE/PCE). © 2016 Société Française de Pharmacologie et de Thérapeutique.

The human respiratory gate

NASA Technical Reports Server (NTRS)

Eckberg, Dwain L.

2003-01-01

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches.

PubMed

Unger, Thomas; Paulis, Ludovit; Sica, Domenic A

2011-11-01

The conventional antihypertensive therapies including renin-angiotensin-aldosterone system antagonists (converting enzyme inhibitors, receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), diuretics, β-blockers, and calcium channel blockers are variably successful in achieving the challenging target blood pressure values in hypertensive patients. Difficult to treat hypertension is still a commonly observed problem world-wide. A number of drugs are considered to be used as novel therapies for hypertension. Renalase supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially aldosterone antagonists (aldosterone synthase inhibitors and novel selective mineralocorticoid receptor blockers) are considered an option in resistant hypertension. In addition, the aldosterone antagonists as well as (pro)renin receptor blockers or AT(2) receptor agonists might attenuate end-organ damage. This array of medications has now been complemented by a number of new approaches of non-pharmacological strategies including vaccination, genomic interference, controlled breathing, baroreflex activation, and probably most successfully renal denervation techniques. However, the progress on innovative therapies seems to be slow and the problem of resistant hypertension and proper blood pressure control appears to be still persisting. Therefore the regimens of currently available drugs are being fine-tuned, resulting in the establishment of several novel fixed-dose combinations including triple combinations with the aim to facilitate proper blood pressure control. It remains an exciting question which approach will confer the best blood pressure control and risk reduction in this tricky disease.

Effects of a contraceptive containing drospirenone and ethinyl estradiol on blood pressure and autonomic tone: a prospective controlled clinical trial.

PubMed

Nisenbaum, Marcelo Gil; de Melo, Nilson Roberto; Giribela, Cassiana Rosa Galvão; de Morais, Tércio Lemos; Guerra, Grazia Maria; de Angelis, Katia; Mostarda, Cristiano; Baracat, Edmund Chada; Consolim-Colombo, Fernanda Marciano

2014-04-01

The use of combined oral contraceptives has been associated with an increased risk of adverse cardiovascular events. Whether these drugs alter cardiac autonomic nervous system control is not completely determined. To evaluate the effect of a contraceptive containing 20mcg of ethinyl estradiol and 3mg of drospirenone on the heart rate variability, baroreflex sensitivity and blood pressure of healthy women. Prospective controlled trial with 69 healthy women allocated in two groups: 36 volunteers under oral combined contraceptive use and 33 volunteers using of non-hormonal contraceptive methods. Subjects were tested before the introduction of the contraceptive method and 6 months after its use. For data acquisition, we used continuous non-invasive beat-to-beat blood pressure curve recordings. Multiple ANOVA was used to determine differences between groups and moments and p< 0.05 was considered statistically significant. At baseline, there were no differences in demographic and autonomic parameters between groups. Comparing cardiac sympatho-vagal modulation, baroreceptor sensitivity and blood pressure measurements between baseline and after 6 months, no significant difference was detected in each group or between groups. A contraceptive containing 20mcg of ethinyl estradiol and 3mg of drospirenone causes no significant changes in clinical, hemodynamic and autonomic parameters of normal women. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Resting Sympathetic Baroreflex Sensitivity in Subjects with Low and High Tolerance to Central Hypovolemia Induced by Lower Body Negative Pressure

DTIC Science & Technology

2014-06-01

high tolerance to central hypovolemia induced by lower body negative pressure Carmen Hinojosa-Laborde1*, Kathy L. Ryan1, Caroline A. Rickards2 and...patients with high tolerance. Using lower body negative pressure (LBNP) as an experimental model to induce central hypovolemia, we have shown that...hypovolemia is associated with mainte- nance of adequate perfusion pressure (i.e., arterial blood pres- sure) to vital organs. Therefore, we hypothesize that

Evaluation of cardiovascular risks of spaceflight does not support the NASA bioastronautics critical path roadmap.

PubMed

Convertino, Victor A; Cooke, William H

2005-09-01

Occurrence of serious cardiac dysrhythmias and diminished cardiac and vascular function are the primary cardiovascular risks of spaceflight identified in the 2005 NASA Bioastronautics Critical Path Roadmap. A review of the literature was conducted on experimental results and observational data obtained from spaceflight and relevant ground simulation studies that addressed occurrence of cardiac dysrhythmias, cardiac contractile and vascular function, manifestation of asymptomatic cardiovascular disease, orthostatic intolerance, and response to exercise stress. Based on data from astronauts who have flown in space, there is no compelling experimental evidence to support significant occurrence of cardiac dysrhythmias, manifestation of asymptomatic cardiovascular disease, or reduction in myocardial contractile function. Although there are post-spaceflight data that demonstrate lower peripheral resistance in astronauts who become presyncopal compared with non-presyncopal astronauts, it is not clear that these differences are the result of decreased vascular function. However, the evidence of postflight orthostatic intolerance and reduced exercise capacity is well substantiated by both spaceflight and ground experiments. Although attenuation of baroreflex function(s) may contribute to postflight orthostatic instability, a primary mechanism of orthostatic intolerance and reduced exercise capacity is reduced end-diastolic and stroke volume associated with lower blood volumes and consequent cardiac remodeling. Data from the literature on the current population of astronauts support the notion that the primary cardiovascular risks of spaceflight are compromised hemodynamic responses to central hypovolemia resulting in reduced orthostatic tolerance and exercise capacity rather than occurrence of cardiac dysrhythmias, reduced cardiac contractile and vascular function, or manifestation of asymptomatic cardiovascular disease. These observations warrant a critical review and revision of the 2005 Bioastronautics Critical Path Roadmap.

Cardioprotective Properties of Aerobic and Resistance Training Against Myocardial Infarction.

PubMed

Barboza, C A; Souza, G I H; Oliveira, J C M F; Silva, L M; Mostarda, C T; Dourado, P M M; Oyama, L M; Lira, F S; Irigoyen, M C; Rodrigues, B

2016-06-01

We evaluated the effects of aerobic and resistance exercise training on ventricular morphometry and function, physical capacity, autonomic function, as well as on ventricular inflammatory status in trained rats prior to myocardial infarction. Male Wistar rats were divided into the following groups: sedentary+Sham, sedentary+myocardial infarction, aerobic trained+myocardial infarction, and resistance trained+myocardial infarction. Sham and myocardial infarction were performed after training periods. In the days following the surgeries, evaluations were performed. Aerobic training prevents aerobic (to a greater extent) and resistance capacity impairments, ventricular dysfunction, baroreflex sensitivity and autonomic disorders (vagal tonus decrease and sympathetic tonus increase) triggered by myocardial infarction. Resistance training was able to prevent negative changes to aerobic and resistance capacity (to a greater extent) but not to ventricular dysfunction, and it prevented cardiovascular sympathetic increments. Additionally, both types of training reduced left ventricle inflammatory cytokine concentration. Our results suggest that aerobic and, for the first time, dynamic resistance training were able to reduce sympathetic tonus to the heart and vessels, as well as preventing the increase in pro-inflammatory cytokine concentrations in the left ventricle of trained groups. These data emphasizes the positive effects of aerobic and dynamic resistance training on the prevention of the negative changes triggered by myocardial infarction. © Georg Thieme Verlag KG Stuttgart · New York.

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

PubMed Central

Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

2016-01-01

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

Validity and Usefulness of `Wearable Blood Pressure Sensing' for Detection of Inappropriate Short-Term Blood Pressure Variability in the Elderly

NASA Astrophysics Data System (ADS)

Iijima, Katsuya; Kameyama, Yumi; Akishita, Masahiro; Ouchi, Yasuyoshi; Yanagimoto, Shintaro; Imai, Yasushi; Yahagi, Naoki; Lopez, Guillaume; Shuzo, Masaki; Yamada, Ichiro

An increase in short-term blood pressure (BP) variability is a characteristic feature in the elderly. It makes the management of hemodynamics more difficult, because it is frequently seen disturbed baro-reflex function and increased arterial stiffness, leading to isolated systolic hypertension. Large BP variability aggravates hypertensive target organ damage and is an independent risk factor for the cardiovascular (CV) events in elderly hypertensive patients. Therefore, appropriate control in BP is indispensable to manage lifestyle-related diseases and to prevent subsequent CV events. In addition, accumulating recent reports show that excessive BP variability is also associated with a decline in cognitive function and fall in the elderly. In the clinical settings, we usually evaluate their health condition, mainly with single point BP measurement using cuff inflation. However, unfortunately we are not able to find the close changes in BP by the traditional way. Here, we can show our advantageous approach of continuous BP monitoring using newly developing device `wearable BP sensing' without a cuff stress in the elderly. The new device could reflect systolic BP and its detailed changes, in consistent with cuff-based BP measurement. Our new challenge suggests new possibility of its clinical application with high accuracy.

A Proposed Study Examining Individual Differences in Temporal Profiles of Cardiovascular Responses to Head Down Tilt During Fluid Loading

NASA Technical Reports Server (NTRS)

Cowings, Patricia; Toscano, William; Winther, Sean; Martinez, Jacqueline; Dominguez, Margaret

2012-01-01

Susceptibility of healthy astronauts to orthostatic hypotension and presyncope is exacerbated upon return from spaceflight. The effect of altered gravity during space flight and planetary transition on human cardiovascular function is of critical importance to maintenance of astronaut health and safety. Hypovolemia, reduced plasma volume, is suspected to play an important role in cardiovascular deconditioning following exposure to spaceflight, which may lead to increased peripheral resistance, attenuated arterial baroreflex, and changes in cardiac function. A promising countermeasure for post-flight orthostatic intolerance is fluid loading used to restore lost plasma volume by giving crew salt tablets and water prior to re-entry. The main purpose of the proposed study is to define the temporal profile of cardiac responses to simulated 0-G conditions before and following a fluid loading countermeasure. 8 men and 8 women will be tested during 4 hour exposures at 6o head down tilt (HDT). Each subject will be given two exposures to HDT on separate days, one with and one without fluid loading (one liter of 0.9% saline solution). Stand tests (orthostatic stress) will be done before and after each HDT. Cardiac measures will be obtained with both impedance cardiography and echo ultrasound

Relationship between Vitamin D Status and Autonomic Nervous System Activity

PubMed Central

Burt, Morton G.; Mangelsdorf, Brenda L.; Stranks, Stephen N.; Mangoni, Arduino A.

2016-01-01

Vitamin D deficiency is associated with increased arterial stiffness. However, the mechanisms underlying this association have not been clarified. The aim was to investigate whether changes in autonomic nervous system activity could underlie an association between 25 hydroxy vitamin D and arterial stiffness. A total of 49 subjects (age = 60 ± 8 years, body mass index = 26.7 ± 4.6 kg/m2, 25 hydroxy vitamin D = 69 ± 22 nmol/L) underwent measurements of pulse wave velocity (PWV) and augmentation index (AIx), spontaneous baroreflex sensitivity, plasma metanephrines and 25 hydroxy vitamin D. Subjects with 25 hydroxy vitamin D ≤ 50 nmol/L were restudied after 200,000 International Units 25 hydroxy vitamin D. Plasma metanephrine was positively associated with AIx (p = 0.02) independent of age, sex, smoking and cholesterol and negatively associated with 25 hydroxy vitamin D (p = 0.002) independent of age, sex and season. In contrast, there was no association between baroreflex sensitivity and 25 hydroxy vitamin D (p = 0.54). Treatment with vitamin D increased 25 hydroxy vitamin D from 43 ± 5 to 96 ± 24 nmol/L (p < 0.0001) but there was no significant change in plasma metanephrine (115 ± 25 vs. 99 ± 39 pmol/L, p = 0.12). We conclude that as plasma metanephrine was negatively associated with 25 hydroxy vitamin D and positively with AIx, it could mediate an association between these two variables. This hypothesis should be tested in larger interventional studies. PMID:27649235

Autonomic dysfunction with early respiratory syncytial virus-related infection.

PubMed

Stock, Claire; Teyssier, Georges; Pichot, Vincent; Goffaux, Philippe; Barthelemy, Jean-Claude; Patural, Hugues

2010-08-25

Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (alpha LF, alpha HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group (p<0.05). RSV infection in neonates is associated with profound central autonomic dysfunction. The potentially fatal consequence stresses the importance of maintaining prolonged cardiopulmonary monitoring. Copyright 2010 Elsevier B.V. All rights reserved.

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle.

PubMed

Valenti, Vitor E; de Abreu, Luiz Carlos; Sato, Monica A; Ferreira, Celso; Adami, Fernando; Fonseca, Fernando L A; Xavier, Valdelias; Godoy, Moacir; Monteiro, Carlos B; Vanderlei, Luiz Carlos M; Saldiva, Paulo H N

2012-03-30

Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 μL) injection into the 4th V. Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.

Heart Rate Turbulence Parameters Correlate with Post-PVC Changes in Muscle Sympathetic Activity

PubMed Central

Segerson, Nathan M.; Wasmund, Stephen L.; Abedin, Moeen; Pai, Rakesh K.; Daccarett, Marcos; Akoum, Nazem; Wall, T. Scott; Klein, Richard C.; Freedman, Roger A.; Hamdan, Mohamed H.

2007-01-01

Background Heart rate turbulence (HRT) has been shown to be vagally-mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) following a premature ventricular contraction (PVC) remains unclear. Objective We sought to evaluate the relationship between HRT and the changes in peripheral SNA following PVCs. Methods We recorded post-ganglionic muscle SNA during ECG monitoring in 8 patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during 1) the dominant burst following the PVC (Dominant-Burst Area), and 2) the 10 seconds following the dominant burst (Post-Burst SNA). Results The mean TO was 0.1±4.6% and the mean TS was 6.1±6.6. The Dominant-Burst Area negatively correlated with TO (-0.50, p=0.0002). The Post-Burst SNA showed a significant positive correlation with TO (r=0.44, p=0.001) and a negative correlation with TS (r=-0.42, p=0.002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. Conclusions Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease. PMID:17341389

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

PubMed Central

2012-01-01

Background Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). Methods We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 μL) injection into the 4th V. Results Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. Conclusion We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity. PMID:22463380

Intracranial baroreflex yielding an early cushing response in human.

PubMed

Schmidt, E A; Czosnyka, Z; Momjian, S; Czosnyka, M; Bech, R A; Pickard, J D

2005-01-01

The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

PDE3A mutations cause autosomal dominant hypertension with brachydactyly.

PubMed

Maass, Philipp G; Aydin, Atakan; Luft, Friedrich C; Schächterle, Carolin; Weise, Anja; Stricker, Sigmar; Lindschau, Carsten; Vaegler, Martin; Qadri, Fatimunnisa; Toka, Hakan R; Schulz, Herbert; Krawitz, Peter M; Parkhomchuk, Dmitri; Hecht, Jochen; Hollfinger, Irene; Wefeld-Neuenfeld, Yvette; Bartels-Klein, Eireen; Mühl, Astrid; Kann, Martin; Schuster, Herbert; Chitayat, David; Bialer, Martin G; Wienker, Thomas F; Ott, Jürg; Rittscher, Katharina; Liehr, Thomas; Jordan, Jens; Plessis, Ghislaine; Tank, Jens; Mai, Knut; Naraghi, Ramin; Hodge, Russell; Hopp, Maxwell; Hattenbach, Lars O; Busjahn, Andreas; Rauch, Anita; Vandeput, Fabrice; Gong, Maolian; Rüschendorf, Franz; Hübner, Norbert; Haller, Hermann; Mundlos, Stefan; Bilginturan, Nihat; Movsesian, Matthew A; Klussmann, Enno; Toka, Okan; Bähring, Sylvia

2015-06-01

Cardiovascular disease is the most common cause of death worldwide, and hypertension is the major risk factor. Mendelian hypertension elucidates mechanisms of blood pressure regulation. Here we report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (HTNB). The syndrome features brachydactyly type E (BDE), severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation and death from stroke before age 50 years when untreated. In vitro analyses of mesenchymal stem cell-derived vascular smooth muscle cells (VSMCs) and chondrocytes provided insights into molecular pathogenesis. The mutations increased protein kinase A-mediated PDE3A phosphorylation and resulted in gain of function, with increased cAMP-hydrolytic activity and enhanced cell proliferation. Levels of phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed PDE3A deserves scrutiny as a therapeutic target for the treatment of hypertension.

Nine months in space: effects on human autonomic cardiovascular regulation.

PubMed

Cooke, W H; Ames JE, I V; Crossman, A A; Cox, J F; Kuusela, T A; Tahvanainen, K U; Moon, L B; Drescher, J; Baisch, F J; Mano, T; Levine, B D; Blomqvist, C G; Eckberg, D L

2000-09-01

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

Carotid-cardiac baroreflex influence on forearm vascular resistance during low level LBNP

NASA Technical Reports Server (NTRS)

Ludwig, David

1990-01-01

Twelve healthy males were tested at low levels of lower body negative pressure (LBNP) with and without artificial stimulation of the carotid-cardiac baroreceptors. The carotid-cardiac baroreceptors were stimulated by applying a pressure of 10 mmHg to the carotid artery via a pressurized neck chamber. During the procedure, forearm blood flow (FBF) and forearm vascular resistance (FVR) were measured using a Whitney mercury silastic strain gauge technique. FBF decreased while FVR increased with increased intensity of LBNP. Both FBF and FVR were unaffected by carotid-cardiac baroreceptor stimulation.

[An automatic system controlled by microcontroller for carotid sinus perfusion].

PubMed

Yi, X L; Wang, M Y; Fan, Z Z; He, R R

2001-08-01

To establish a new method for controlling automatically the carotid perfusion pressure. A cheap practical automatic perfusion unit based on AT89C2051 micro controller was designed. The unit, LDB-M perfusion pump and the carotid sinus of an animal constituted an automatic perfusion system. This system was able to provide ramp and stepwise updown perfusion pattern and has been used in the research of baroreflex. It can insure the precision and reproducibility of perfusion pressure curve, and improve the technical level in corresponding medical field.

Joint symbolic dynamics for the assessment of cardiovascular and cardiorespiratory interactions

PubMed Central

Baumert, Mathias; Javorka, Michal; Kabir, Muammar

2015-01-01

Beat-to-beat variations in heart period provide information on cardiovascular control and are closely linked to variations in arterial pressure and respiration. Joint symbolic analysis of heart period, systolic arterial pressure and respiration allows for a simple description of their shared short-term dynamics that are governed by cardiac baroreflex control and cardiorespiratory coupling. In this review, we discuss methodology and research applications. Studies suggest that analysis of joint symbolic dynamics provides a powerful tool for identifying physiological and pathophysiological changes in cardiovascular and cardiorespiratory control. PMID:25548272

Joint symbolic dynamics for the assessment of cardiovascular and cardiorespiratory interactions.

PubMed

Baumert, Mathias; Javorka, Michal; Kabir, Muammar

2015-02-13

Beat-to-beat variations in heart period provide information on cardiovascular control and are closely linked to variations in arterial pressure and respiration. Joint symbolic analysis of heart period, systolic arterial pressure and respiration allows for a simple description of their shared short-term dynamics that are governed by cardiac baroreflex control and cardiorespiratory coupling. In this review, we discuss methodology and research applications. Studies suggest that analysis of joint symbolic dynamics provides a powerful tool for identifying physiological and pathophysiological changes in cardiovascular and cardiorespiratory control.

Valsalva maneuver: Insights into baroreflex modulation of human sympathetic activity

NASA Technical Reports Server (NTRS)

Smith, Michael L.; Eckberg, Dwain L.; Fritsch, Janice M.; Beightol, Larry A.; Ellenbogen, Kenneth A.

1991-01-01

Valsalva's maneuver, voluntary forced expiration against a closed glottis, is a well-characterized research tool, used to assess the integrity of human autonomic cardiovascular control. Valsalva straining provokes a stereotyped succession of alternating positive and negative arterial pressure and heart rate changes mediated in part by arterial baroreceptors. Arterial pressure changes result primarily from fluctuating levels of venous return to the heart and changes of sympathetic nerve activity. Muscle sympathetic activity was measured directly in nine volunteers to explore quantitatively the relation between arterial pressure and human sympathetic outflow during pressure transients provoked by controlled graded Valsalva maneuvers. Our results underscore several properties of sympathetic regulation during Valsalva straining. First, muscle sympathetic nerve activity changes as a mirror image of changes in arterial pressure. Second, the magnitude of sympathetic augmentation during Valsalva straining predicts phase 4 arterial pressure elevations. Third, post-Valsalva sympathetic inhibition persists beyond the return of arterial and right atrial pressures to baseline levels which reflects an alteration of the normal relation between arterial pressure and muscle sympathetic activity. Therefore, Valsalva straining may have some utility for investigating changes of reflex control of sympathetic activity after space flight; however, measurement of beat-to-beat arterial pressure is essential for this use. The utility of this technique in microgravity can not be determined from these data. Further investigations are necessary to determine whether these relations are affected by the expansion of intrathoracic blood volume associated with microgravity.

Recent advances in the pathophysiology of arterial hypertension: potential implications for clinical practice.

PubMed

Hering, Dagmara; Trzebski, Andrzej; Narkiewicz, Krzysztof

2017-03-01

Hypertension remains a major and growing public health problem associated with the greatest global rate of cardiovascular morbidity and mortality. Although numerous factors contribute to poor control of blood pressure (BP) and to pseudoresistance (eg, unawareness, lifestyle habits, nonadherence to medication, insufficient treatment, drug‑induced hypertension, undiagnosed secondary causes), true resistant hypertension (RH) is reported in 10.1% of patients treated for elevated BP. While the mechanisms underlying RH remain complex and not entirely understood, sympathetic activation involved in the pathophysiology of hypertension, disease progression, and adverse complications is further augmented in patients with drug‑resistant hypertension. The well‑established contribution of neurogenic component of hypertension has led to the introduction of new alternative therapies aimed specifically at modulating central and neural reflexes mechanisms involved in BP control. Although clinical benefits of lowering BP with renal denervation, baroreflex activation therapy, carotid body denervation, central arteriovenous anastomosis, and deep brain stimulation have advanced our knowledge on uncontrolled hypertension, the variable BP response has prompted extensive ongoing research to define predictors of treatment effectiveness and further investigation of pathophysiology of RH. Very recently, research on the role of vasopressinergic neurons, masked tachycardia, and impaired brain neural activity has provided novel insights into hypertension. This review briefly summarizes the role of the centrally mediated sympathetic nervous system in hypertension, the therapeutic strategies that distinctively target impaired neural reflex mechanisms, and potential implications for future clinical research and therapies.

A new technique for simultaneous monitoring of electrocardiogram and walking cadence

NASA Technical Reports Server (NTRS)

Hausdorff, J. M.; Forman, D. E.; Pilgrim, D. M.; Rigney, D. R.; Wei, J. Y.; Goldberger, A. L. (Principal Investigator)

1992-01-01

A new technique for simultaneously recording continuous electrocardiographic (ECG) data and walking step rate (cadence) is described. The ECG and gait signals are recorded on 2 channels of an ambulatory Holter monitor. Footfall is detected using ultrathin, force-sensitive foot switches and is frequency modulated. The footfall signal provides an indication of the subject's activity (walking or standing), as well as the instantaneous walking rate. Twenty-three young and elderly subjects were studied to demonstrate the use of this ECG and gait recorder. High-quality gait signals were obtained in all subjects, and the effects of walking on the electrocardiogram were assessed. Initial investigation revealed the following findings: (1) Although walking rates were similar in young and elderly subjects, the elderly had both decreased heart rate (HR) variability (p < 0.005) and increased cadence variability (p < 0.0001). (2) Overall, there was an inverse relation between HR and cadence variability (r = -0.73). Three elderly subjects with no known cardiac disease had HR and cadence variability similar to those of the young, whereas elderly subjects with history of congestive heart failure were among those with the lowest HR variability and the highest cadence variability. (3) Low-frequency (approximately equal to 0.1 Hz) HR oscillations (frequently observed during standing) persisted during walking in all young subjects. (4) In some subjects, both step rate and HR oscillated at the same low frequency (approximately equal to 0.1 Hz) previously identified with autonomic control of the baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS).

Therapeutic perspectives in hypertension: novel means for renin–angiotensin–aldosterone system modulation and emerging device-based approaches

PubMed Central

Unger, Thomas; Paulis, Ludovit; Sica, Domenic A.

2011-01-01

The conventional antihypertensive therapies including renin–angiotensin–aldosterone system antagonists (converting enzyme inhibitors, receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), diuretics, β-blockers, and calcium channel blockers are variably successful in achieving the challenging target blood pressure values in hypertensive patients. Difficult to treat hypertension is still a commonly observed problem world-wide. A number of drugs are considered to be used as novel therapies for hypertension. Renalase supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially aldosterone antagonists (aldosterone synthase inhibitors and novel selective mineralocorticoid receptor blockers) are considered an option in resistant hypertension. In addition, the aldosterone antagonists as well as (pro)renin receptor blockers or AT2 receptor agonists might attenuate end-organ damage. This array of medications has now been complemented by a number of new approaches of non-pharmacological strategies including vaccination, genomic interference, controlled breathing, baroreflex activation, and probably most successfully renal denervation techniques. However, the progress on innovative therapies seems to be slow and the problem of resistant hypertension and proper blood pressure control appears to be still persisting. Therefore the regimens of currently available drugs are being fine-tuned, resulting in the establishment of several novel fixed-dose combinations including triple combinations with the aim to facilitate proper blood pressure control. It remains an exciting question which approach will confer the best blood pressure control and risk reduction in this tricky disease. PMID:21951628

Sympathetic nervous system and the kidney in hypertension.

PubMed

DiBona, Gerald F

2002-03-01

Long-term control of arterial pressure has been attributed to the kidney by virtue of its ability to couple the regulation of blood volume to the maintenance of sodium and water balance by the mechanisms of pressure natriuresis and diuresis. In the presence of a defect in renal excretory function, hypertension arises as the consequence of the need for an increase in arterial pressure to offset the abnormal pressure natriuresis and diuresis mechanisms, and to maintain sodium and water balance. There is growing evidence that an important cause of the defect in renal excretory function in hypertension is an increase in renal sympathetic nerve activity (RSNA). First, increased RSNA is found in animal models of hypertension and hypertensive humans. Second, renal denervation prevents or alleviates hypertension in virtually all animal models of hypertension. Finally, increased RSNA results in reduced renal excretory function by virtue of effects on the renal vasculature, the tubules, and the juxtaglomerular granular cells. The increase in RSNA is of central nervous system origin, with one of the stimuli being the action of angiotensin II, probably of central origin. By acting on brain stem nuclei that are important in the control of peripheral sympathetic vasomotor tone (e.g. rostral ventrolateral medulla), angiotensin II increases the basal level of RSNA and impairs its arterial baroreflex regulation. Therefore, the renal sympathetic nerves may serve as the link between central sympathetic nervous system regulatory sites and the kidney in contributing to the renal excretory defect in the development of hypertension.

Specifying Software Behavior for Requirements and Design

DTIC Science & Technology

2013-01-01

e.g., Behavior Hiding is comprised of the Function Driver and Shared Services modules. Blacked-out modules, which are concerned with mechanisms for...and Shared Services modules. “The Func- tion Driver Module consists of a set of modules called Func- tion Drivers; each Function Driver is the sole...system environment. Functions that capture the rules determining these output values specify that behavior. The Shared Services module concerns aspects of

A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep

PubMed Central

Herrera, E A; Kane, A D; Hansell, J A; Thakor, A S; Allison, B J; Niu, Y; Giussani, D A

2012-01-01

Virtually nothing is known about the effects on fetal physiology of xanthine oxidase inhibition. This is despite maternal treatment with the xanthine oxidase inhibitor allopurinol being considered in human complicated pregnancy to protect the infant's brain from excessive generation of ROS. We investigated the in vivo effects of maternal treatment with allopurinol on fetal cardiovascular function in ovine pregnancy in late gestation. Under anaesthesia, pregnant ewes and their singleton fetus were instrumented with vascular catheters and flow probes around an umbilical and a fetal femoral artery at 118 ± 1 dGA (days of gestational age; term ca. 145 days). Five days later, mothers were infused i.v. with either vehicle (n= 11) or allopurinol (n= 10). Fetal cardiovascular function was stimulated with increasing bolus doses of phenylephrine (PE) following maternal vehicle or allopurinol. The effects of maternal allopurinol on maternal and fetal cardiovascular function were also investigated following fetal NO blockade (n= 6) or fetal β1-adrenergic antagonism (n= 7). Maternal allopurinol led to significant increases in fetal heart rate, umbilical blood flow and umbilical vascular conductance, effects abolished by fetal β1-adrenergic antagonism but not by fetal NO blockade. Maternal allopurinol impaired fetal α1-adrenergic pressor and femoral vasopressor responses and enhanced the gain of the fetal cardiac baroreflex. These effects of maternal allopurinol were restored to control levels during fetal NO blockade. Maternal treatment with allopurinol induced maternal hypotension, tachycardia and acid–base disturbance. We conclude that maternal treatment with allopurinol alters in vivo maternal, umbilical and fetal vascular function via mechanisms involving NO and β1-adrenergic stimulation. The evidence suggests that the use of allopurinol in clinical practice should be approached with caution. PMID:22331413

Clinical review: Cardiovascular consequences of ovarian disruption: a focus on functional hypothalamic amenorrhea in physically active women.

PubMed

O'Donnell, Emma; Goodman, Jack M; Harvey, Paula J

2011-12-01

Evidence indicates that hypoestrogenemia is linked with accelerated progression of atherosclerosis. Premenopausal women presenting with ovulatory disruption due to functional hypothalamic amenorrhea (FHA) are characterized by hypoestrogenemia. One common and reversible form of FHA in association with energy deficiency is exercise-associated amenorrhea (EAA). Articles were found via PubMed search for both original and review articles based on peer review publications between 1974 and 2011 reporting on cardiovascular changes in women with FHA, with emphasis placed on women with EAA. Despite participation in regular exercise training, hypoestrogenic women with EAA demonstrate paradoxical changes in cardiovascular function, including endothelial dysfunction, a known permissive factor for the progression and development of atherosclerosis. Such alterations suggest that the beneficial effects of regular exercise training on vascular function are obviated in the face of hypoestrogenemia. The long-term cardiovascular consequences of altered vascular function in response to ovulatory disruption in women with EAA remain to be determined. Retrospective data, however, suggest premature development and progression of coronary artery disease in older premenopausal women reporting a history of hypothalamic ovulatory disruption. Importantly, in women with EAA, estrogen therapy, folic acid supplementation without change in menstrual status, and resumption of menses restores endothelial function. In this review, we focus on the influence of hypoestrogenemia in association with energy deficiency in mediating changes in cardiovascular function in women with EAA, including endothelial function, regional blood flow, lipid profile, and autonomic control of blood pressure, heart rate, and baroreflex sensitivity. The influence of exercise training is also considered. With the premenopausal years typically considered to be cardioprotective in association with normal ovarian function, ovarian disruption in women with EAA is of importance. Further investigation of the short-term, and potentially long-term, cardiovascular consequences of hypoestrogenemia in women with EAA is recommended.

Effect of dynamic exercise on human carotid-cardiac baroreflex latency

NASA Technical Reports Server (NTRS)

Potts, J. T.; Raven, P. B.

1995-01-01

We compared the beat-to-beat responses of heart rate (HR) after brief activation of carotid baroreceptors in resting humans with the responses obtained during mild-to-moderate levels of dynamic exercise [25 and 50% of peak O2 uptake (VO2peak)] to investigate the effect of exercise on baroreflex latency. Carotid baroreceptors were activated by a pressure pulse (5 s) of neck suction (NS, -80 Torr) and neck pressure (NP, +40 Torr) during held expiration. At rest the peak change in HR to NS/NP occurred during the first several heartbeats (1st-3rd beat), whereas during mild and moderate exercise peak HR responses occurred near the end of the NS/NP pulse (6th-8th beat). In contrast, time (s) to the peak change in HR was not different between rest and exercise (P > 0.05). Reflex tachycadia to NP progressively decreased during exercise (17 +/- 3, 10 +/- 1, and 4 +/- 1% of control, rest vs. 25% VO2peak, vs. 50% VO2peak, respectively, P < 0.05), and a strong positive correlation was found between the magnitude of the reflex tachycardia and a measure of HR variability (cardiac vagal tone index, r = 0.74, P < 0.0001). Reflex bradycardia to NS gradually increased during exercise (13 +/- 2, 17 +/- 2, and 18 +/- 2% of control, rest vs. 25% VO2peak, vs. 50% VO2peak, respectively, P = 0.10) and was negatively correlated with cardiac vagal tone (r = 0.42, P < 0.06).(ABSTRACT TRUNCATED AT 250 WORDS).

Nonlinear identification of the total baroreflex arc.

PubMed

Moslehpour, Mohsen; Kawada, Toru; Sunagawa, Kenji; Sugimachi, Masaru; Mukkamala, Ramakrishna

2015-12-15

The total baroreflex arc [the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP)] is known to exhibit nonlinear behaviors. However, few studies have quantitatively characterized its nonlinear dynamics. The aim of this study was to develop a nonlinear model of the sympathetically mediated total arc without assuming any model form. Normal rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned, the carotid sinus regions were isolated and attached to a servo-controlled piston pump, and the AP and sympathetic nerve activity (SNA) were measured. CSP was perturbed using a Gaussian white noise signal. A second-order Volterra model was developed by applying nonparametric identification to the measurements. The second-order kernel was mainly diagonal, but the diagonal differed in shape from the first-order kernel. Hence, a reduced second-order model was similarly developed comprising a linear dynamic system in parallel with a squaring system in cascade with a slower linear dynamic system. This "Uryson" model predicted AP changes 12% better (P < 0.01) than a linear model in response to new Gaussian white noise CSP. The model also predicted nonlinear behaviors, including thresholding and mean responses to CSP changes about the mean. Models of the neural arc (the system relating CSP to SNA) and peripheral arc (the system relating SNA to AP) were likewise developed and tested. However, these models of subsystems of the total arc showed approximately linear behaviors. In conclusion, the validated nonlinear model of the total arc revealed that the system takes on an Uryson structure. Copyright © 2015 the American Physiological Society.

Nonlinear identification of the total baroreflex arc

PubMed Central

Moslehpour, Mohsen; Kawada, Toru; Sunagawa, Kenji; Sugimachi, Masaru

2015-01-01

The total baroreflex arc [the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP)] is known to exhibit nonlinear behaviors. However, few studies have quantitatively characterized its nonlinear dynamics. The aim of this study was to develop a nonlinear model of the sympathetically mediated total arc without assuming any model form. Normal rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned, the carotid sinus regions were isolated and attached to a servo-controlled piston pump, and the AP and sympathetic nerve activity (SNA) were measured. CSP was perturbed using a Gaussian white noise signal. A second-order Volterra model was developed by applying nonparametric identification to the measurements. The second-order kernel was mainly diagonal, but the diagonal differed in shape from the first-order kernel. Hence, a reduced second-order model was similarly developed comprising a linear dynamic system in parallel with a squaring system in cascade with a slower linear dynamic system. This “Uryson” model predicted AP changes 12% better (P < 0.01) than a linear model in response to new Gaussian white noise CSP. The model also predicted nonlinear behaviors, including thresholding and mean responses to CSP changes about the mean. Models of the neural arc (the system relating CSP to SNA) and peripheral arc (the system relating SNA to AP) were likewise developed and tested. However, these models of subsystems of the total arc showed approximately linear behaviors. In conclusion, the validated nonlinear model of the total arc revealed that the system takes on an Uryson structure. PMID:26354845

Postural Change Alters Autonomic Responses to Breath-Holding

PubMed Central

Taneja, Indu; Medow, Marvin S.; Clarke, Debbie; Ocon, Anthony; Stewart, Julian M.

2011-01-01

We used breath-holding during inspiration as a model to study the effect of pulmonary stretch on sympathetic nerve activity. Twelve healthy subjects (7 females, 5 males; 19–27 yrs) were tested while they performed an inspiratory breath-hold, both supine and during a 60° head-up tilt (HUT 60). Heart rate (HR), mean arterial blood pressure (MAP), respiration, muscle sympathetic nerve activity (MSNA), oxygen saturation (SaO2) and end tidal carbon dioxide (ETCO2) were recorded. Cardiac output (CO) and total peripheral resistance (TPR) were calculated. While breath-holding, ETCO2 increased significantly from 41±2 to 60±2 Torr during supine (p<0.05) and 38±2 Torr to 58±2 during HUT60 (p<0.05); SaO2 decreased from 98±1.5% to 95±1.4% supine, and from 97±1.5% to 94±1.7% during HUT60 (p=NS). MSNA showed three distinctive phases - a quiescent phase due to pulmonary stretch associated with decreased MAP, HR, CO and TPR; a second phase of baroreflex-mediated elevated MSNA which was associated with recovery of MAP and HR only during HUT60; CO and peripheral resistance returned to baseline while supine and HUT60; a third phase of further increased MSNA activity related to hypercapnia and associated with increased TPR. Breath-holding results in initial reductions of MSNA, MAP and HR by the pulmonary stretch reflex followed by increased sympathetic activity related to the arterial baroreflex and chemoreflex. PMID:20012144

Histological analysis of the aortic nerve in the rat raised in space (Rapid communication on Neurolab Project).

PubMed

Yamasaki, M; Shimizu, T; Miyake, M; Miyamoto, Y; Waki, H; Katsuda, S I; Oishi, H; Nagayama, T; Katahira, K; Wago, H; Okochi, T; Kaneko, M; Matsumoto, S; Mukai, C; Nagaoka, S; Izumi, T; Yanagawa, K; Uemura, M; O-ishi, H

1998-11-01

To study development of the aortic nerve baroreflex under conditions of microgravity, we examined the cross section of the left aortic nerve (LAN), which is the afferent of the baroreflex, in the neonate rats aged 25 days raised in microgravity on the space shuttle Columbia (flight:FLT group) for 16 days. In this paper, we report a part of the result obtained from the data of the myelinated fibers of LAN analyzed with an electron microscope. Two kind of ground control groups were compared to the FLT group; one was asynchronous ground control (AGC) group where the rats were housed in the same cage as that on the shuttle, and the other was vivarium(VIV) group where the rats were housed in a commercial cage. The LANs in each group were extirpated the from rats perfused with a fixative and embedded for histological analysis. We observed the transverse sections of LAN and took pictures of several areas (magnified to x 2K to x 200K). No irregular myelination was found in all fibers of FLT group when they were compared with two control groups. The thickness of myelin of the maximally myelinated fibers were 0.55 +/- 0.17 micrometer in FLT(n=5), 0.45 +/- 0.10 micrometer in AGC(n=5), and O.47 +/- 0.06 micrometer meter in VIV(n=5). There was no significant difference among three groups (unpared t-test). The results suggest that there is no effect of space environment on the myelin formation of each nerve fiber in the aortic nerve.

Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia

PubMed Central

Hansen, Jim; Sander, Mikael

2003-01-01

Acute exposure to hypoxia causes chemoreflex activation of the sympathetic nervous system. During acclimatization to high altitude hypoxia, arterial oxygen content recovers, but it is unknown to what degree sympathetic activation is maintained or normalized during prolonged exposure to hypoxia. We therefore measured sympathetic nerve activity directly by peroneal microneurography in eight healthy volunteers (24 ± 2 years of age) after 4 weeks at an altitude of 5260 m (Chacaltaya, Bolivian Andes) and at sea level (Copenhagen). The subjects acclimatized well to altitude, but in every subject sympathetic nerve activity was highly elevated at altitude vs. sea level (48 ± 5 vs. 16 ± 3 bursts min−1, respectively, P < 0.05), coinciding with increased mean arterial blood pressure (87 ± 3 vs. 77 ± 2 mmHg, respectively, P < 0.05). To examine the underlying mechanisms, we administered oxygen (to eliminate chemoreflex activation) and saline (to reduce cardiopulmonary baroreflex deactivation). These interventions had minor effects on sympathetic activity (48 ± 5 vs. 38 ± 4 bursts min−1, control vs. oxygen + saline, respectively, P < 0.05). Moreover, sympathetic activity was still markedly elevated (37 ± 5 bursts min−1) when subjects were re-studied under normobaric, normoxic and hypervolaemic conditions 3 days after return to sea level. In conclusion, acclimatization to high altitude hypoxia is accompanied by a striking and long-lasting sympathetic overactivity. Surprisingly, chemoreflex activation by hypoxia and baroreflex deactivation by dehydration together could account for only a small part of this response, leaving the major underlying mechanisms unexplained. PMID:12563015

The renal nerves in chronic heart failure: efferent and afferent mechanisms

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

Cardiovascular and Postural Control Interactions during Hypergravity: Effects on Cerebral Autoregulation in Males and Females

NASA Astrophysics Data System (ADS)

Goswami, Nandu; Blaber, Andrew; Bareille, Marie-Pierre; Beck, Arnaud; Avan, Paul; Bruner, Michelle; Hinghofer-Szalkay, Helmut

2012-07-01

Orthostatic intolerance remains a problem upon return to Earth from the microgravity environment of spaceflight. A variety of conditions including hypovolemia, cerebral vasoconstriction, cerebral or peripheral vascular disease, or cardiac arrhythmias may result in syncope if the person remains upright. Current research indicates that there is a greater dependence on visual and somatosensory information at the beginning of space flight with a decreased otolith gain during prolonged space flight (Herault et al., 2002). The goal of the research is to further our understanding of the fundamental adaptive homeostatic mechanisms involved in gravity related changes in cardiovascular and postural function. Cardiovascular, cerebrovascular, and postural sensory motor control systems in male and female participants before, during, and after exposure to graded levels of hyper-G were investigated. Hypotheses: 1) Activation of skeletal muscle pump will be directly related to the degree of orthostatic stress. 2) Simultaneous measurement of heart rate, blood pressure and postural sway will predict cardio-postural stability. Blood pressure and heart rate (means and variability), postural sway, center of pressure (COP), baroreflex function, calf blood flow, middle cerebral artery blood flow, non-invasive intracranial pressure measurements, and two-breath CO2 were measured. Results from the study will be used to provide an integrated insight into mechanisms of cardio-postural control and cerebral autoregulation, which are important aspects of human health in flights to Moon, Mars and distant planets.

Baroreflex responses and LBNP tolerance following exercise training

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Thompson, C. A.; Eckberg, D. L.; Fritsch, J. M.; Mack, G. W.; Nadel, E. R.

1990-01-01

The hypothesis that endurance exercise training designed to increase aerobic capacity results in reduced orthostatic tolerance due to alterations of blood-pressure controlling mechanisms was reexamined using a specially designed training in which tolerance to orthostasis and the primary mechanisms associated with the blood-pressure control could be measured before and after the increase in aerobic capacity. Results demonstrate that maximal oxygen uptake can be significantly elevated in individuals of average fit without reducing lower body negative pressure tolerance. The exercise training was found to cause a resting bradycardia, which had no effect on the cardiac vagal reflex response.

A quantitative method for studying human arterial baroreflexes

NASA Technical Reports Server (NTRS)

Eckberg, Dwain L.; Fritsch, Janice M.; Goble, Ross L.

1991-01-01

A new system is described that delivers precise, stereotyped pressure changes to the human neck and elicits neurally-mediated heart rate changes. The centerpiece of this system is a Silastic chamber that is strapped to the anterior neck. This chamber is connected to a stepping-motor-controlled bellows assembly. A strain-gauge transducer measures the intensity of pressure changes. The entire system is controlled by microprocessors, and both stimuli and responses are displayed on a digital oscilloscope. The end-product of this system is a reproducible baroreceptor stimulus-cardiac response relation that can be recorded rapidly and safely in astronauts in space.

Gender Differences in Baroreflex Sensitivity after Bed Rest

NASA Technical Reports Server (NTRS)

Arzeno, Natalia M.; Stenger, M. B.; Ribeiro, L. C.; Lee, S. M.; Platts, S. H.

2009-01-01

Two potential contributing factors to post-spaceflight orthostatic intolerance are decreases in baroreflex sensitivity (BRS) and sympathetic nervous system response. The purpose of this study was to examine the shape of the BRS curve and sympathetic response to a wide range of blood pressures (BP) before and during 6 head-down bed rest (BR). METHODS: Normal volunteers were tested one day before BR (20M, 1 0F) and near BR days 30 (20M, 10F), 60 (16M, 8F), and 90 (1 0M, 5F). BP was pharmacologically manipulated by 10-min infusions of phenylephrine (PE) and sodium nitroprusside (SNP) at 3 increasing concentrations with a 20-min rest between PE and SNP. Electrocardiogram and continuous finger blood pressure were recorded. A blood sample was drawn at the end of each infusion to measure plasma norepinephrine levels. The spontaneous baroreflex slope (SBS), a measure of BRS, was calculated as the slope of a sequence of 3 or more beats in which the systolic BP (SBP) and following R-R interval (RR) both increased or decreased. The data included saturated responses at the upper but not the lower end of the BP range. Mean response curves were constructed using second-order mixed model analysis. Results are based on term significance in the models. RESULTS RR: RR was lower during BR than pre BR (p<0.001). Pre BR males were modeled by a linear RR response to SBP (p=0.000) while females had a quadratic response which saturated at high SBP (p=0.019). By day 30, both genders were modeled by a linear response; compared to males, females had an attenuated (lower slope) RR response to changes in SBP (p=0.031). SBS: SBS vs SBP analysis showed a lower SBS during BR (p<0.001) when compared to pre BR. Females had a higher SBS than males pre BR (p=0.006). Females exhibited saturating SBS at higher SBP (p=0.016) on day 30, while males were modeled by a linear SBS response to SBP (p=0.035). NE: Females had different NE response to diastolic BP than males pre BR (p=0.035) and on day 30 (p=0.005). CONCLUSION: NE, RR and SBS responses to BP are affected by gender and BR. Not only do gender and BR baseline differences exist, but gender and BR also influence the slope and saturation of the BRS curves. Attenuated and saturating RR and SBS responses, as well as differences in baseline values, may contribute to the higher rates of orthostatic intolerance in women and after bed rest.

Relative sideband amplitudes versus modulation index for common functions using frequency and phase modulation. [for design and testing of communication system

NASA Technical Reports Server (NTRS)

Stocklin, F.

1973-01-01

The equations defining the amplitude of sidebands resulting from either frequency modulation or phase modulation by either square wave, sine wave, sawtooth or triangular modulating functions are presented. Spectral photographs and computer generated tables of modulation index vs. relative sideband amplitudes are also included.

Caffeine delays autonomic recovery following acute exercise.

PubMed

Bunsawat, Kanokwan; White, Daniel W; Kappus, Rebecca M; Baynard, Tracy

2015-11-01

Impaired autonomic recovery of heart rate (HR) following exercise is associated with an increased risk of sudden death. Caffeine, a potent stimulator of catecholamine release, has been shown to augment blood pressure (BP) and sympathetic nerve activity; however, whether caffeine alters autonomic function after a bout of exercise bout remains unclear. In a randomized, crossover study, 18 healthy individuals (26 ± 1 years; 23.9 ± 0.8 kg·m(-2)) ingested caffeine (400 mg) or placebo pills, followed by a maximal treadmill test to exhaustion. Autonomic function and ventricular depolarization/repolarization were determined using heart rate variability (HRV) and corrected QT interval (QTc), respectively, at baseline, 5, 15, and 30 minutes post-exercise. Maximal HR (HRmax) was greater with caffeine (192 ± 2 vs. 190 ± 2 beat·min(-1), p < 0.05). During recovery, HR, mean arterial pressure (MAP), and diastolic blood pressure (DBP) remained elevated with caffeine (p < 0.05). Natural log transformation of low-to-high frequency ratio (LnLF/LnHF) of HRV was increased compared with baseline at all time points in both trials (p < 0.05), with less of an increase during 5 and 15 minutes post-exercise in the caffeine trial (p < 0.05). QTc increased from baseline at all time points in both trials, with greater increases in the caffeine trial (p < 0.05). Caffeine ingestion disrupts post-exercise autonomic recovery because of increased sympathetic nerve activity. The prolonged sympathetic recovery time could subsequently hinder baroreflex function during recovery and disrupt the stability of autonomic function, potentiating a pro-arrhythmogenic state in young adults. © The European Society of Cardiology 2014.

Stratification of pediatric heart failure on the basis of neurohormonal and cardiac autonomic nervous activities in patients with congenital heart disease.

PubMed

Ohuchi, Hideo; Takasugi, Hisashi; Ohashi, Hiroyuki; Okada, Yoko; Yamada, Osamu; Ono, Yasuo; Yagihara, Toshikatsu; Echigo, Shigeyuki

2003-11-11

Stratification of pediatric patients with congenital heart disease (CHD) has been based on their hemodynamics and/or functional capacity. Our purpose was to compare cardiac autonomic nervous activity (CANA) and neurohormonal activities (NHA) with postoperative status in stable CHD patients with biventricular physiology. We divided 379 subjects (297 CHD patients, 28 dilated cardiomyopathy patient, and 54 control subjects) into 4 subgroups according to New York Heart Association (NYHA) class (1.3+/-0.7) and measured various CANA and NHA indices. Stepwise decreases in baroreflex sensitivity (BRS), heart rate variability (HRV), adrenergic imaging, and vital capacity (VC) were observed in proportion to functional capacity in normal to NYHA II patients (P<0.001). However, there were no differences in these indices between NYHA II and III+IV groups, whereas a stepwise proportional increase in NHA indices was observed in these groups (P<0.001). Natriuretic peptides differentiated all NYHA classes. BRS, HRV, and VC were greater in the adult patients than in the child patients (P<0.05 to 0.01), although the functional class in adult patients was lower. Cardiac surgeries resulted in low BRS and VC, and the VC reduction independently determined a small HRV. Even if functional class and ejection fraction were comparable, CANA and brain natriuretic peptide were lower in CHD patients than in dilated cardiomyopathy patients (P<0.05 to 0.001). CANA and NHA indices are useful to stratify mild and severe heart failure in stable postoperative CHD patients, respectively. However, careful attention should be paid to age- and surgery-related influences on these indices.

Accounting for respiration is necessary to reliably infer Granger causality from cardiovascular variability series.

PubMed

Porta, Alberto; Bassani, Tito; Bari, Vlasta; Pinna, Gian D; Maestri, Roberto; Guzzetti, Stefano

2012-03-01

This study was designed to demonstrate the need of accounting for respiration (R) when causality between heart period (HP) and systolic arterial pressure (SAP) is under scrutiny. Simulations generated according to a bivariate autoregressive closed-loop model were utilized to assess how causality changes as a function of the model parameters. An exogenous (X) signal was added to the bivariate autoregressive closed-loop model to evaluate the bias on causality induced when the X source was disregarded. Causality was assessed in the time domain according to a predictability improvement approach (i.e., Granger causality). HP and SAP variability series were recorded with R in 19 healthy subjects during spontaneous and controlled breathing at 10, 15, and 20 breaths/min. Simulations proved the importance of accounting for X signals. During spontaneous breathing, assessing causality without taking into consideration R leads to a significantly larger percentage of closed-loop interactions and a smaller fraction of unidirectional causality from HP to SAP. This finding was confirmed during paced breathing and it was independent of the breathing rate. These results suggest that the role of baroreflex cannot be correctly assessed without accounting for R.

Obstructive Sleep Apnoea/Hypopnoea Syndrome and Hypertension

PubMed Central

Al-Abri, Mohammed A; Al-Hashmi, Khamis M

2008-01-01

The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a common disorder, affecting around 2–4% of the middle-aged population. There is a strong association between OSAHS and hypertension, based on animal, large epidemiological and interventional studies. The epidemiological studies have shown a dose-response relationship between apnoea/hypopnoea index (AHI) and the risk of developing hypertension. Different mechanisms may have a role in the process of elevated blood pressure in OSAHS. Sympathetic activity is increased in OSAHS patients during sleep and wakefulness. This increase in sympathetic activity is probably due to activation of baroreflexes and chemoreflexes by frequent arousals and hypoxaemia a result of apnoea or hypopnoea events. Continuous positive airway pressure (CPAP) has been shown to reduce sympathetic stimulation and blood pressure in OSAHS patients. Altered endothelial function may also have a role in the pathogenesis of hypertension in OSAHS subjects. Reduction of nitric oxide (NO) production and increase in the formation of free radicals may be responsible for the impairment of the vasodilatation of micro-vasculature in these subjects as a result of hypoxaemia. It has been shown that effective CPAP therapy has a reversible effect on endothelial dysfunction. PMID:21748071

Ambulatory blood pressure profiles in familial dysautonomia.

PubMed

Goldberg, Lior; Bar-Aluma, Bat-El; Krauthammer, Alex; Efrati, Ori; Sharabi, Yehonatan

2018-02-12

Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability. We analyzed 24-h ambulatory blood pressure monitoring recordings in 22 patients with FD. Information about medications, disease severity, renal function (estimated glomerular filtration, eGFR), pulmonary function (forced expiratory volume in 1 s, FEV1) and an index of blood pressure variability (standard deviation of systolic pressure) were analyzed. The mean (± SEM) 24-h blood pressure was 115 ± 5.6/72 ± 2.0 mmHg. The diurnal blood pressure variability was high (daytime systolic pressure standard deviation 22.4 ± 1.5 mmHg, nighttime 17.2 ± 1.6), with a high frequency of a non-dipping pattern (16 patients, 73%). eGFR, use of medications, FEV1, and disability scores were unrelated to the degree of blood pressure variability or to dipping status. This FD cohort had normal average 24-h blood pressure, fluctuating blood pressure, and a high frequency of non-dippers. Although there was evidence of renal dysfunction based on eGFR and proteinuria, the ABPM profile was unrelated to the measures of end organ dysfunction or to reported disability.

Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat

PubMed Central

Talman, William T.; Dragon, Deidre Nitschke; Jones, Susan Y.; Moore, Steven A.; Lin, Li-Hsien

2015-01-01

Lesions that remove neurons expressing neurokinin-1 (NK1) receptors from the nucleus tractus solitarii (NTS) without removing catecholaminergic neurons lead to loss of baroreflexes, labile arterial pressure, myocardial lesions and sudden death. Because destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) may also cause lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions associated with lability are not dependent on damage to neurons with NK1 receptors but would also occur when TH neurons in NTS are targeted. To rid the NTS of TH neurons we microinjected anti-dopamine β-hydroxylase conjugated to saporin (anti-DBH-SAP, 42ng/200nl) into the NTS. After injection of the toxin unilaterally, immunofluorescent staining confirmed that anti-DBH-SAP decreased the number of neurons and fibers that contain TH and DBH in the injected side of the NTS while sparing neuronal elements expressing NK1 receptors. Bilateral injections in 8 rats led to significant lability of arterial pressure. For example, on day 8 standard deviation of mean arterial pressure was 16.8 ± 2.5 mmHg when compared with a standard deviation of 7.83 ± 0.33 mmHg in 6 rats in which phosphate buffered saline (PBS) had been injected bilaterally. Two rats died suddenly at 5 and 8 days after anti-DBH-SAP injection. Seven treated animals demonstrated microscopic myocardial necrosis as reported in animals with lesions of NTS neurons expressing NK1 receptors. Thus, cardiac and cardiovascular effects of lesions directed toward catecholamine neurons of the NTS are similar to those following damage directed toward NK1 receptor containing neurons. PMID:22484855

Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome.

PubMed

Straznicky, Nora E; Grima, Mariee T; Sari, Carolina I; Eikelis, Nina; Lambert, Gavin W; Nestel, Paul J; Richards, Katrina; Dixon, John B; Schlaich, Markus P; Lambert, Elisabeth A

2015-07-01

Insulin resistance is associated with blunted sympathetic nervous system (SNS) response to carbohydrate ingestion which may contribute to postprandial hypotension and impaired body weight homeostasis. This study was conducted to examine the effects of pharmacological insulin sensitization on whole-body norepinephrine kinetics during a standard 75-g oral glucose tolerance test (OGTT) in obese, insulin resistant subjects with metabolic syndrome. Un-medicated individuals (n=42, mean age 56±0.8 yrs, body mass index 34±0.6 kg/m(2)) were randomised to 12-weeks pioglitazone (PIO, 15 mg for 6 weeks, then 30 mg daily) or placebo using a double-blind, parallel group design. Whole-body norepinephrine kinetics (arterial norepinephrine concentration, calculated spillover and clearance rates), spontaneous cardiac baroreflex sensitivity, heart rate and blood pressure were measured at times 0, 30, 60, 90 and 120 minutes during OGTT. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M) and Matsuda index. PIO increased clamp derived glucose utilisation by 35% (P<0.001) and there were concurrent reductions in inflammatory status and plasma triglycerides (P<0.05). Fasting norepinephrine kinetic parameters were unaltered. PIO treatment was associated with lower plasma insulin incursions, greater reduction in diastolic blood pressure and enhanced baroreflex sensitivity during OGTT (P all <0.05). The overall norepinephrine spillover response (AUC(0-120)) increased significantly in the PIO group (group × time interaction, P=0.04), with greatest increment at 30 minutes post-glucose (101±38 ng/min at baseline versus 241±48 ng/min post treatment, P=0.04) and correlated with percent improvement in M. PIO enhances the early postprandial SNS response to carbohydrate ingestion. Copyright © 2015. Published by Elsevier Inc.

Nonlinear identification of the total baroreflex arc: higher-order nonlinearity

PubMed Central

Moslehpour, Mohsen; Kawada, Toru; Sunagawa, Kenji; Sugimachi, Masaru

2016-01-01

The total baroreflex arc is the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP). The nonlinear dynamics of this system were recently characterized. First, Gaussian white noise CSP stimulation was employed in open-loop conditions in normotensive and hypertensive rats with sectioned vagal and aortic depressor nerves. Nonparametric system identification was then applied to measured CSP and AP to establish a second-order nonlinear Uryson model. The aim in this study was to assess the importance of higher-order nonlinear dynamics via development and evaluation of a third-order nonlinear model of the total arc using the same experimental data. Third-order Volterra and Uryson models were developed by employing nonparametric and parametric identification methods. The R2 values between the AP predicted by the best third-order Volterra model and measured AP in response to Gaussian white noise CSP not utilized in developing the model were 0.69 ± 0.03 and 0.70 ± 0.03 for normotensive and hypertensive rats, respectively. The analogous R2 values for the best third-order Uryson model were 0.71 ± 0.03 and 0.73 ± 0.03. These R2 values were not statistically different from the corresponding values for the previously established second-order Uryson model, which were both 0.71 ± 0.03 (P > 0.1). Furthermore, none of the third-order models predicted well-known nonlinear behaviors including thresholding and saturation better than the second-order Uryson model. Additional experiments suggested that the unexplained AP variance was partly due to higher brain center activity. In conclusion, the second-order Uryson model sufficed to represent the sympathetically mediated total arc under the employed experimental conditions. PMID:27629885

Losartan reduces oxidative stress within the rostral ventrolateral medulla of rats with renovascular hypertension.

PubMed

Nishi, Erika E; Bergamaschi, Cássia T; Oliveira-Sales, Elizabeth B; Simon, Karin A; Campos, Ruy R

2013-07-01

Previous studies showed that the microinjection of antioxidants or the overexpression of superoxide dismutase within the rostral ventrolateral medulla (RVLM) reduces hypertension and sympathoexcitation in the 2-kidney, 1-clip (2K-1C) model. In this study, we hypothesized that angiotensin II (ANG II) type 1 receptor (AT1R) is involved in the oxidative stress within the RVLM and contributes to cardiovascular dysfunction in renovascular hypertension. Losartan (30mg/kg/day, oral gavage) was administered for 7 consecutive days by week 5 after implantation of the clip (gap width = 0.2mm). Mean arterial pressure, baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated. Superoxide production was evaluated by dihydroethidium (DHE) staining within the RVLM and within a control area. Systemic oxidative stress was characterized by measurement of thiobarbituric acid reactive substances (TBARS) and total glutathione (tGSH) in the blood. AT1R blockade significantly (P < 0.05) reduced hypertension by approximately 20% (n = 11) and sympathoexcitation to the kidneys by approximately 41% (n = 6) in the 2K-1C rats. Losartan treatment increased the baroreflex sensitivity of rSNA to pressor (67%) and depressor (140%) stimuli in the 2K-1C rats. AT1R blockade caused a significant (66%) reduction in DHE staining within the RVLM but not within the control area, reduced plasma TBARS (from 1.6±0.1 to 1.0±0.1 nmol/ml), and increased tGSH (from 3.4±0.4 to 5.2±0.3 μmol/g Hb) in the 2K-1C group only. Our findings suggest that the beneficial effects of ANG II blockade in renovascular hypertension are partly due to preferential reduction of oxidative stress in the RVLM.

Effects of Sinoaortic Denervation on Hemodynamic Parameters During Natural Sleep in Rats

PubMed Central

Silveira, Neide P.; Moreira, Edson D.; Drager, Luciano F.; Silva, Gustavo J. J.; Krieger, Eduardo M.

2008-01-01

Study Objectives: To analyze the role of arterial baroreflex on hemodynamic changes during synchronized and desynchronized sleep phases of natural sleep in rats. Design: Experimental study. Setting: Laboratory. Participants: Seventeen male Wistar rats. Interventions: No intervention (control, n = 8) or sinoaortic denervation (SAD, n = 9). Measurements and Results: Sleep phases were monitored by electrocorticogram, and blood pressure was measured directly by a catheter in the carotid artery. Cardiac output, as well as total and regional vascular resistances, were determined by measuring the subdiaphragmatic aorta and iliac artery flows with Doppler flow probes, respectively. In contrast to the control group, the SAD group had a strong reduction in blood pressure (−19.9% ± 2.6% vs −0.7% ± 2.1%) during desynchronized sleep, and cardiac output showed an exacerbated reduction (−10.4% ± 3.5% vs 1.1% ± 1.7%). In SAD rats, total vascular resistance decreased during desynchronized sleep (−10.1% ± 3.5% vs −1.0% ± 1.7%), and the increase in regional vascular resistance observed in the control group was abolished (27.5% ± 8.3% vs −0.8% ± 9.4%). Conclusions: SAD caused profound changes in blood pressure, cardiac output, and total vascular resistance, with a significant increase in muscle vascular resistance during synchronized sleep. Our results suggest that baroreflex plays an important role in maintaining the normal balance of cardiac output and total vascular resistance during sleep. Citation: Silveira NP; Moreira ED; Drager LF; Silva GJJ; Krieger EM. Effects of sinoaortic denervation on hemodynamic parameters during natural sleep in rats. SLEEP 2008;31(3):328-333. PMID:18363308

Effects of Some Indigenous Plants of North Karnataka (India) on Cardiovascular and Glucose Regulatory Systems in Alloxan-Induced Diabetic Rats.

PubMed

Das, Kusal K; Chadchan, Kailash S; Reddy, R Chandramouli; Biradar, M S; Kanthe, Pallavi S; Patil, Bheemshetty S; Ambekar, Jeevan G; Bagoji, Ishwar B; Das, Swastika

2017-11-08

Kenaf (Hibiscus cannabinus Linn, Pundi), Chick pea (Cicer arietinum Linn, Chana) and Prickly lettuce (Lactuca scariola Linn, Hattaraki) leaves are a few of indigenous plants which are routinely consumed by the people of north Karnataka in the diet. Studies on these plants showed some potential anti-diabetic efficacies. To examine the effect of leaves extracts of Hibiscus cannabinus Linn, Cicer arietinum Linn and Lactuca scariola Linn on cardiovascular integrity, glucose homeostasis and oxygen sensing cell signaling mechanisms in alloxan induced diabetic rats. In vitro and in vivo tests on glucose regulatory systems and molecular markers such as - NOS3, HIF- 1α and VEGF were conducted in alloxan induced diabetic rats supplemented with all the three plant extracts. Electrophysiological analysis (HRV, LF: HF ratio, baroreflex sensitivity, BRS) and histopathogy of myocardial tissues and elastic artery were evaluated in diabetic rats treated with L. scariola linn. Out of these three plant extracts, Lactuca scariola Linn supplementation showed significant beneficial effects on glucose homeostasis and oxygen sensing cell signaling pathways in alloxaninduced diabetic rats. Furthermore, effects of sub chronic supplementation of Lactuca scariola Linn aqueous extracts showed significant improvement in sympatho-vagal balance in diabetic rats by increase of Heart Rate Variability (HRV) and regaining of Baroreflex Sensitivity (BRS). These results were also corroborated with myocardial and elastic artery histopathology of Lactuca scariola Linn supplemented diabetic rats. These findings indicate an adaptive pathway for glucose homeostasis, oxygen sensing cell signaling mechanisms and cardio protective actions in alloxan - induced diabetic rats supplemented with Lactuca scariola Linn extracts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modelling the interaction among several mechanisms in the short-term arterial pressure control.

PubMed

Ursino, M

2000-01-01

A Mathematical model of the short-term arterial pressure control in humans is presented. It includes a six-compartment description of the vascular system, an elastance variable model of the pulsating heart, two groups of baroreceptors (high-pressure or sinoaortic baroreceptors and low-pressure or cardiopulmonary baroreceptors), the efferent activity in the sympathetic nerves and in the vagus, and the response of four distinct effectors (heart period, systemic peripheral resistance, systemic venous unstressed volume and heart contractility). Several experimental results reported in the physiological literature can be reproduced with the model quite well. The examples presented in this work include the effect of combined sympathetic and vagal stimulation on heart rate, the baroreflex response to mild and severe acute haemorrhages, and the baroreflex response to ventricular pacing at different rates performed during atrioventricular block. The results suggest that: i) The sympathetic nerves and the vagus interact linearly in regulating heart period. The apparent negative interaction observed experimentally can be ascribed merely to the hyperbolic relationship which links heart rate to heart period. ii) The cardiopulmonary baroafferents play a significant role in the control of systemic arterial pressure during mild haemorrhages (lower than 3-4% of the overall blood volume). In this range, they may allow arterial pressure to be maintained at its normal level without the intervention of the sinoaortic baroreceptors. In contrast, the sinoaortic baroreceptors become the major responsible of the observed cardiovascular adjustments during more severe haemorrhages, when the role of cardiopulmonary baroreceptors becomes progressively exhausted. iii) The stability margin of the closed-loop system is quite low. Increasing the static gain of the baroreceptors or reducing the rate-dependent component may result in self-sustained oscillations similar to Mayer waves.

A comparison of autonomic responses in humans induced by two simulation models of weightlessness: lower body positive pressure and 6 degrees head-down tilt.

PubMed

Fu, Q; Sugiyama, Y; Kamiya, A; Mano, T

2000-04-12

Six-degree head-down tilt (HDT) is well accepted as an effective weightlessness model in humans. However, some researchers utilized lower body positive pressure (LBPP) to simulate the cardiovascular and renal effects of a decreased gravitational stress. In order to determine whether LBPP was a suitable model for simulated weightlessness, we compared the differences between these two methods. Ten healthy males, aged 21-41 years, were subjected to graded LBPP at 10, 20 and 30 mmHg, as well as 6 degrees HDT. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve along with cardiovascular variables. We found that MSNA decreased by 27% to a similar extent both at low levels of LBPP (10 and 20 mmHg) and HDT. However, at a high level of LBPP (30 mmHg), MSNA tended to increase. Mean arterial pressure was elevated significantly by 11% (10 mmHg) at 30 mmHg LBPP, but remained unchanged at low levels of LBPP and HDT. Heart rate did not change during the entire LBPP and HDT procedures. Total peripheral resistance markedly increased by 36% at 30 mmHg LBPP, but decreased by 9% at HDT. Both stroke volume and cardiac output tended to decrease at 30 mmHg LBPP, but increased at HDT. These results suggest that although both LBPP and HDT induce fluid shifts from the lower body toward the thoracic compartment, autonomic responses are different, especially at LBPP greater than 20 mmHg. We note that high levels of LBPP (>20 mmHg) activate not only cardiopulmonary and arterial baroreflexes, but also intramuscular mechanoreflexes, while 6 degrees HDT only activates cardiopulmonary baroreflexes. We conclude that LBPP is not a suitable model for simulated weightlessness in humans.

Acute baroreflex resetting: differential control of pressure and nerve activity.

PubMed

Drummond, H A; Seagard, J L

1996-03-01

This study evaluated acute resetting of carotid baroreflex control of arterial blood pressure and renal or thoracic sympathetic nerve activity in thiopental-anesthetized mongrel dogs with the use of a vascularly isolated carotid sinus preparation, the experimental model used previously to characterize acute resetting in carotid baroreceptor afferent fibers. Carotid baroreceptors were conditioned with a pulsatile pressure for 20 minutes at three pressure ranges: low (50 to 75 mm Hg), mid (100 to 125), or high (150 to 175). Blood pressure and nerve activity were recorded in response to slow ramp increases in sinus pressure; nonlinear regression and best-fit analyses were used for determination of curve fit parameters of the blood pressure and nerve activity versus sinus pressure response curves. Carotid sinus pressure thresholds for blood pressure and renal nerve activity responses at all conditioning pressures were significantly different; however, only the pressure threshold for thoracic nerve activity at the low conditioning pressure was significantly different from the responses at other conditioning pressures. Average renal activity resetting (0.506 +/- 0.072) was significantly greater than blood pressure resetting (0.335 +/- 0.046) in the same dogs, and thoracic activity (0.200 +/- 0.057) was not different from blood pressure resetting (0.194 +/- 0.031) in the same dogs. In a previous investigation, our laboratory had demonstrated that type 1 carotid baroreceptors acutely reset at a value of about 0.15. These results indicate that (1) renal and thoracic nerve activities and blood pressure acutely reset to a greater degree than type 1 carotid baroreceptors and that (2) renal activity acutely resets to a greater degree than blood pressure and thoracic nerve activity.

Effects of long-term exercise training on autonomic control in myocardial infarction patients.

PubMed

Martinez, Daniel G; Nicolau, José C; Lage, Rony L; Toschi-Dias, Edgar; de Matos, Luciana D N J; Alves, Maria Janieire N N; Trombetta, Ivani C; Dias da Silva, Valdo J; Middlekauff, Holly R; Negrão, Carlos E; Rondon, Maria U P B

2011-12-01

Autonomic dysfunction, including baroreceptor attenuation and sympathetic activation, has been reported in patients with myocardial infarction (MI) and has been associated with increased mortality. We tested the hypotheses that exercise training (ET) in post-MI patients would normalize arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA), and long-term ET would maintain the benefits in BRS and MSNA. Twenty-eight patients after 1 month of uncomplicated MI were randomly assigned to 2 groups, ET (MI-ET) and untrained. A normal control group was also studied. ET consisted of three 60-minute exercise sessions per week for 6 months. We evaluated MSNA (microneurography), blood pressure (automatic oscillometric method), heart rate (ECG), and spectral analysis of RR interval, systolic arterial pressure (SAP), and MSNA. Baroreflex gain of SAP-RR interval and SAP-MSNA were calculated using the α-index. At 3 to 5 days and 1 month after MI, MSNA and low-frequency SAP were significantly higher and BRS significantly lower in MI patients when compared with the normal control group. ET significantly decreased MSNA (bursts per 100 heartbeats) and the low-frequency component of SAP and significantly increased the low-frequency component of MSNA and BRS of the RR interval and MSNA. These changes were so marked that the differences between patients with MI and the normal control group were no longer observed after ET. MSNA and BRS in the MI-untrained group did not change from baseline over the same time period. ET normalizes BRS, low-frequency SAP, and MSNA in patients with MI. These improvements in autonomic control are maintained by long-term ET. These findings highlight the clinical importance of this nonpharmacological therapy based on ET in the long-term treatment of patients with MI.

Reduced heart rate response after premature ventricular contraction depending on severity of atrial fibrillation symptoms - Analysis on heart rate turbulence in atrial fibrillation patients.

PubMed

Makimoto, Hisaki; Blockhaus, Christian; Meyer, Christian; Lin, Tina; Jungen, Christiane; Eickholt, Christian; Clasen, Lukas; Schmidt, Jan; Kurt, Muhammed; Müller, Patrick; Shin, Dong-In; Kelm, Malte; Fürnkranz, Alexander

2018-03-01

The severity of symptoms during atrial fibrillation (AF) may be influenced by heart rate and blood pressure variation, due to irregular beats and the related adaptations in baroreflex sensitivity. This study investigated whether heart rate turbulence (HRT) as a reflection of baroreflex sensitivity is related to symptom severity during AF. Ninety-seven patients (pts) who underwent electrophysiological study were enrolled. Consecutive 56 pts had paroxysmal AF (21 with milder symptoms [EHRA I or II; Group-M], 35 with severe symptoms [EHRA III or IV; Group-S]), and 41 age-matched controls without AF were included. After delivering a single ventricular extrastimulus during sinus rhythm and repeating the process 10 times, the quantification of HRT was performed by measuring turbulence onset (TO: heart rate acceleration) and turbulence slope (TS: rate of heart rate deceleration). Group-M pts showed significantly diminished TO as compared to controls and Group-S pts (P = 0.012). There was no significant difference of the TS between the 3 groups. Given that a TO ≥ 0% or TS ≤ 2.5 ms/RR was considered abnormal, Group-M pts showed significantly higher incidences of abnormal HRT as compared to controls and Group-S pts (71% vs 40% vs 21%, respectively, P = 0.0012). Regression analysis demonstrated an independent and significant association between a diminished TO and milder AF symptoms (P < 0.05). The usual heart rate acceleration after premature ventricular contraction is significantly diminished in pts with milder AF symptoms as compared to pts with severe AF symptoms. The mechanism of association between this diminished response and symptoms should be further investigated.

Baroreflex sensitivity to predict malignant middle cerebral artery infarction.

PubMed

Sykora, Marek; Steiner, Thorsten; Rocco, Andrea; Turcani, Peter; Hacke, Werner; Diedler, Jennifer

2012-03-01

Hemicraniectomy has been shown to be an effective treatment of life-threatening edema (LTE) in malignant middle cerebral artery infarction when performed early. Identifying patients who will develop LTE is therefore imperative. We hypothesize that autonomic shift toward sympathetic dominance may relate to LTE formation. We aimed to investigate the predictive potential of baroreflex sensitivity (BRS) as a marker of autonomic balance for calculating the course of large middle cerebral artery infarction. Patients with middle cerebral artery infarction >2/3 of the territory and BRS measurement at admission were analyzed. BRS was estimated using the cross-correlational method. Demographic, clinical, and radiological data including stroke severity, infarct size, and basal ganglia involvement were recorded. Malignant course with LTE was defined as clinical deterioration and midline shift ≥5 mm in the first 48 hours. Eighteen (62.8%) patients developed LTE. Patients with LTE had lower BRS (2.3 versus 4.4 mm Hg/ms, P=0.007), larger infarcts (214 versus 144 mL, P=0.03), more frequent involvement of the basal ganglia (14 versus 4, P=0.03), and more often underwent thrombolysis combined with endovascular intervention (6 versus 0, P=0.04). In a multivariate model, BRS (OR, 0.36; CI, 0.14-0.93; P=0.03) and basal ganglia involvement (OR, 11.53; CI, 1.15-115.9; P=0.04) were independent predictors for LTE. This model correctly classified 86.2% of the malignant cases. Decreased BRS, mirroring sympathetic activation, and basal ganglia involvement were associated with development of malignant course with LTE in large middle cerebral artery infarction. The predictive relevance of our findings needs to be confirmed in further studies.

Prediction of pharmacologically induced baroreflex sensitivity from local time and frequency domain indices of R-R interval and systolic blood pressure signals obtained during deep breathing.

PubMed

Arica, Sami; Firat Ince, N; Bozkurt, Abdi; Tewfik, Ahmed H; Birand, Ahmet

2011-07-01

Pharmacological measurement of baroreflex sensitivity (BRS) is widely accepted and used in clinical practice. Following the introduction of pharmacologically induced BRS (p-BRS), alternative assessment methods eliminating the use of drugs were in the center of interest of the cardiovascular research community. In this study we investigated whether p-BRS using phenylephrine injection can be predicted from non-pharmacological time and frequency domain indices computed from electrocardiogram (ECG) and blood pressure (BP) data acquired during deep breathing. In this scheme, ECG and BP data were recorded from 16 subjects in a two-phase experiment. In the first phase the subjects performed irregular deep breaths and in the second phase the subjects received phenylephrine injection. From the first phase of the experiment, a large pool of predictors describing the local characteristic of beat-to-beat interval tachogram (RR) and systolic blood pressure (SBP) were extracted in time and frequency domains. A subset of these indices was selected using twelve subjects with an exhaustive search fused with a leave one subject out cross validation procedure. The selected indices were used to predict the p-BRS on the remaining four test subjects. A multivariate regression was used in all prediction steps. The algorithm achieved best prediction accuracy with only two features extracted from the deep breathing data, one from the frequency and the other from the time domain. The normalized L2-norm error was computed as 22.9% and the correlation coefficient was 0.97 (p=0.03). These results suggest that the p-BRS can be estimated from non-pharmacological indices computed from ECG and invasive BP data related to deep breathing. Copyright © 2011 Elsevier Ltd. All rights reserved.

Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

NASA Technical Reports Server (NTRS)

Brooks, V. L.; Keil, L. C.

1992-01-01

Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing.

PubMed

O'Leary, D D; Lin, D C; Hughson, R L

1999-09-01

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R-R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R-R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r = 0.76 and r = 0.85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean +/- SEM; 3.5 +/- 0.3 versus 11.2 +/- 1.4 ms mmHg-1; P < 0.01) and spontaneous sequence analysis (10.3 +/- 0.8 versus 31.5 +/- 2.3 ms mmHg-1; P < 0.001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7.9 +/- 1.4 versus 6.7 +/- 0.8 ms mmHg-1; P = 0.27) or spontaneous sequence methods (21.8 +/- 2.7 versus 20.0 +/- 2.1 ms mmHg-1; P = 0.24). BRG was correlated during RB and SB protocols (r = 0.80; P < 0.0001). ARMA and spontaneous BRG estimates were correlated (r = 0.79; P < 0.0001), with spontaneous sequence values being consistently larger (P < 0.0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.

Simulated Microgravity Increases Cutaneous Blood Flow in the Head and Leg of Humans

NASA Technical Reports Server (NTRS)

Stout, M. Shannon; Watenpaugh, Donald E.; Breit, Gregory A.; Hargens, Alan R.

1995-01-01

The cutaneous microcirculation vasodilates during acute 6 degree head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body. Cutaneous microvascular blood flow was measured with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting). Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean +/- SE, p less than 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline througout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p less than 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values. Because hydrostatic effects of HDT increase local arterial pressure at the carotid sinus, baroreflex-mediated withdrawal of sympathetic tone probably contributed to increased microvascular flows at the head and leg during HDT. In the leg baroreflex effects combined with minimal stimulation of local veno-arteriolar and myogenic autoregulatory vasoconstriction to elicit relatively larger and more sustained increases in cutaneous flow during HDT. In the cheek, delayed myogenic vasoconstriction and/or hurmonal effects apparently compensated for flow elevation by 24 h of HDT. Therefore, localized vascular adaptations to gravity probably explain differences in acclimation of lower and upper body blood flow to HDT and actual microgravity.

An integrative approach to inferring biologically meaningful gene modules.

PubMed

Cho, Ji-Hoon; Wang, Kai; Galas, David J

2011-07-26

The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association. We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

Dynamic range of frontoparietal functional modulation is associated with working memory capacity limitations in older adults.

PubMed

Hakun, Jonathan G; Johnson, Nathan F

2017-11-01

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60-77years of age), age was negatively associated with frontoparietal modulation range. Individuals with greater modulation range exhibited more accurate N-Back performance. In addition, despite a lack of significant relationships between N-Back and complex span task performance, range of frontoparietal modulation during the N-Back significantly predicted domain-general estimates of WM capacity. Consistent with previous cross-sectional findings, older individuals with less modulation range exhibited greater activation at the lowest level of task difficulty but less activation at the highest levels of task difficulty. Our results are largely consistent with existing theories of neurocognitive aging (e.g. CRUNCH) but focus attention on dynamic range of functional modulation asa novel marker of WM capacity-limitations in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Morphological integration of anatomical, developmental, and functional postcranial modules in the crab-eating macaque (Macaca fascicularis).

PubMed

Conaway, Mark A; Schroeder, Lauren; von Cramon-Taubadel, Noreen

2018-03-22

Integration and modularity reflect the coordinated action of past evolutionary processes and, in turn, constrain or facilitate phenotypic evolvability. Here, we analyze magnitudes of integration in the macaque postcranium to test whether 20 a priori defined modules are (1) more tightly integrated than random sets of postcranial traits, and (2) are differentiated based on mode of definition, with developmental modules expected to be more integrated than functional or anatomical modules. The 3D morphometric data collected for eight limb and girdle bones for 60 macaques were collated into anatomical, developmental, and functional modules. A resampling technique was used to create random samples of integration values for each module for statistical comparison. Our results found that not all a priori defined modules were more strongly integrated than random samples of postcranial traits and that specific types of modules did not present consistent patterns of integration. Rather, girdle and joint modules were consistently less integrated than limb modules, and forelimb elements were less integrated than hindlimbs. The results suggest that morphometrically complex modules tend to be less integrated than simple limb bones, irrespective of the number of available traits. However, differences in integration of the fore- and hindlimb more likely reflects the multitude of locomotory, feeding, and social functions involved. It remains to be tested whether patterns of integration identified here are primate universals, and to what extent they vary depending on phylogenetic or functional factors. © 2018 Wiley Periodicals, Inc.

Evaluation method for the potential functionome harbored in the genome and metagenome.

PubMed

Takami, Hideto; Taniguchi, Takeaki; Moriya, Yuki; Kuwahara, Tomomi; Kanehisa, Minoru; Goto, Susumu

2012-12-12

One of the main goals of genomic analysis is to elucidate the comprehensive functions (functionome) in individual organisms or a whole community in various environments. However, a standard evaluation method for discerning the functional potentials harbored within the genome or metagenome has not yet been established. We have developed a new evaluation method for the potential functionome, based on the completion ratio of Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules. Distribution of the completion ratio of the KEGG functional modules in 768 prokaryotic species varied greatly with the kind of module, and all modules primarily fell into 4 patterns (universal, restricted, diversified and non-prokaryotic modules), indicating the universal and unique nature of each module, and also the versatility of the KEGG Orthology (KO) identifiers mapped to each one. The module completion ratio in 8 phenotypically different bacilli revealed that some modules were shared only in phenotypically similar species. Metagenomes of human gut microbiomes from 13 healthy individuals previously determined by the Sanger method were analyzed based on the module completion ratio. Results led to new discoveries in the nutritional preferences of gut microbes, believed to be one of the mutualistic representations of gut microbiomes to avoid nutritional competition with the host. The method developed in this study could characterize the functionome harbored in genomes and metagenomes. As this method also provided taxonomical information from KEGG modules as well as the gene hosts constructing the modules, interpretation of completion profiles was simplified and we could identify the complementarity between biochemical functions in human hosts and the nutritional preferences in human gut microbiomes. Thus, our method has the potential to be a powerful tool for comparative functional analysis in genomics and metagenomics, able to target unknown environments containing various uncultivable microbes within unidentified phyla.

Evolution of functional specialization and division of labor.

PubMed

Rueffler, Claus; Hermisson, Joachim; Wagner, Günter P

2012-02-07

Division of labor among functionally specialized modules occurs at all levels of biological organization in both animals and plants. Well-known examples include the evolution of specialized enzymes after gene duplication, the evolution of specialized cell types, limb diversification in arthropods, and the evolution of specialized colony members in many taxa of marine invertebrates and social insects. Here, we identify conditions favoring the evolution of division of labor by means of a general mathematical model. Our starting point is the assumption that modules contribute to two different biological tasks and that the potential of modules to contribute to these tasks is traded off. Our results are phrased in terms of properties of performance functions that map the phenotype of modules to measures of performance. We show that division of labor is favored by three factors: positional effects that predispose modules for one of the tasks, accelerating performance functions, and synergistic interactions between modules. If modules can be lost or damaged, selection for robustness can counteract selection for functional specialization. To illustrate our theory we apply it to the evolution of specialized enzymes coded by duplicated genes.

A Multiscale Closed-Loop Cardiovascular Model, with Applications to Heart Pacing and Hemorrhage

NASA Astrophysics Data System (ADS)

Canuto, Daniel; Eldredge, Jeff; Chong, Kwitae; Benharash, Peyman; Dutson, Erik

2017-11-01

A computational tool is developed for simulating the dynamic response of the human cardiovascular system to various stressors and injuries. The tool couples zero-dimensional models of the heart, pulmonary vasculature, and peripheral vasculature to one-dimensional models of the major systemic arteries. To simulate autonomic response, this multiscale circulatory model is integrated with a feedback model of the baroreflex, allowing control of heart rate, cardiac contractility, and peripheral impedance. The performance of the tool is demonstrated in two scenarios: increasing heart rate by stimulating the sympathetic nervous system, and an acute 10 percent hemorrhage from the left femoral artery.

An integrative approach to inferring biologically meaningful gene modules

PubMed Central

2011-01-01

Background The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association. Results We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. Conclusions The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level. PMID:21791051

HAL/SM system functional design specification. [systems analysis and design analysis of central processing units

NASA Technical Reports Server (NTRS)

Ross, C.; Williams, G. P. W., Jr.

1975-01-01

The functional design of a preprocessor, and subsystems is described. A structure chart and a data flow diagram are included for each subsystem. Also a group of intermodule interface definitions (one definition per module) is included immediately following the structure chart and data flow for a particular subsystem. Each of these intermodule interface definitions consists of the identification of the module, the function the module is to perform, the identification and definition of parameter interfaces to the module, and any design notes associated with the module. Also described are compilers and computer libraries.

Response functions for sine- and square-wave modulations of disparity.

NASA Technical Reports Server (NTRS)

Richards, W.

1972-01-01

Depth sensations cannot be elicited by modulations of disparity that are more rapid than about 6 Hz, regardless of the modulation amplitude. Vergence tracking also fails at similar modulation rates, suggesting that this portion of the oculomotor system is limited by the behavior of disparity detectors. For sinusoidal modulations of disparity between 1/2 to 2 deg of disparity, most depth-response functions exhibit a low-frequency decrease that is not observed with square-wave modulations of disparity.

Pain perception and hypnosis: findings from recent functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-01-01

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

CommWalker: correctly evaluating modules in molecular networks in light of annotation bias.

PubMed

Luecken, M D; Page, M J T; Crosby, A J; Mason, S; Reinert, G; Deane, C M

2018-03-15

Detecting novel functional modules in molecular networks is an important step in biological research. In the absence of gold standard functional modules, functional annotations are often used to verify whether detected modules/communities have biological meaning. However, as we show, the uneven distribution of functional annotations means that such evaluation methods favor communities of well-studied proteins. We propose a novel framework for the evaluation of communities as functional modules. Our proposed framework, CommWalker, takes communities as inputs and evaluates them in their local network environment by performing short random walks. We test CommWalker's ability to overcome annotation bias using input communities from four community detection methods on two protein interaction networks. We find that modules accepted by CommWalker are similarly co-expressed as those accepted by current methods. Crucially, CommWalker performs well not only in well-annotated regions, but also in regions otherwise obscured by poor annotation. CommWalker community prioritization both faithfully captures well-validated communities and identifies functional modules that may correspond to more novel biology. The CommWalker algorithm is freely available at opig.stats.ox.ac.uk/resources or as a docker image on the Docker Hub at hub.docker.com/r/lueckenmd/commwalker/. deane@stats.ox.ac.uk. Supplementary data are available at Bioinformatics online.

Hardware Architecture Study for NASA's Space Software Defined Radios

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Scardelletti, Maximilian C.; Mortensen, Dale J.; Kacpura, Thomas J.; Andro, Monty; Smith, Carl; Liebetreu, John

2008-01-01

This study defines a hardware architecture approach for software defined radios to enable commonality among NASA space missions. The architecture accommodates a range of reconfigurable processing technologies including general purpose processors, digital signal processors, field programmable gate arrays (FPGAs), and application-specific integrated circuits (ASICs) in addition to flexible and tunable radio frequency (RF) front-ends to satisfy varying mission requirements. The hardware architecture consists of modules, radio functions, and and interfaces. The modules are a logical division of common radio functions that comprise a typical communication radio. This paper describes the architecture details, module definitions, and the typical functions on each module as well as the module interfaces. Trade-offs between component-based, custom architecture and a functional-based, open architecture are described. The architecture does not specify the internal physical implementation within each module, nor does the architecture mandate the standards or ratings of the hardware used to construct the radios.

Space Telecommunications Radio Systems (STRS) Hardware Architecture Standard: Release 1.0 Hardware Section

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Kacpura, Thomas J.; Smith, Carl R.; Liebetreu, John; Hill, Gary; Mortensen, Dale J.; Andro, Monty; Scardelletti, Maximilian C.; Farrington, Allen

2008-01-01

This report defines a hardware architecture approach for software-defined radios to enable commonality among NASA space missions. The architecture accommodates a range of reconfigurable processing technologies including general-purpose processors, digital signal processors, field programmable gate arrays, and application-specific integrated circuits (ASICs) in addition to flexible and tunable radiofrequency front ends to satisfy varying mission requirements. The hardware architecture consists of modules, radio functions, and interfaces. The modules are a logical division of common radio functions that compose a typical communication radio. This report describes the architecture details, the module definitions, the typical functions on each module, and the module interfaces. Tradeoffs between component-based, custom architecture and a functional-based, open architecture are described. The architecture does not specify a physical implementation internally on each module, nor does the architecture mandate the standards or ratings of the hardware used to construct the radios.

FamNet: A Framework to Identify Multiplied Modules Driving Pathway Expansion in Plants1

PubMed Central

Tohge, Takayuki; Klie, Sebastian; Fernie, Alisdair R.

2016-01-01

Gene duplications generate new genes that can acquire similar but often diversified functions. Recent studies of gene coexpression networks have indicated that, not only genes, but also pathways can be multiplied and diversified to perform related functions in different parts of an organism. Identification of such diversified pathways, or modules, is needed to expand our knowledge of biological processes in plants and to understand how biological functions evolve. However, systematic explorations of modules remain scarce, and no user-friendly platform to identify them exists. We have established a statistical framework to identify modules and show that approximately one-third of the genes of a plant’s genome participate in hundreds of multiplied modules. Using this framework as a basis, we implemented a platform that can explore and visualize multiplied modules in coexpression networks of eight plant species. To validate the usefulness of the platform, we identified and functionally characterized pollen- and root-specific cell wall modules that multiplied to confer tip growth in pollen tubes and root hairs, respectively. Furthermore, we identified multiplied modules involved in secondary metabolite synthesis and corroborated them by metabolite profiling of tobacco (Nicotiana tabacum) tissues. The interactive platform, referred to as FamNet, is available at http://www.gene2function.de/famnet.html. PMID:26754669

BinTree Seeking: A Novel Approach to Mine Both Bi-Sparse and Cohesive Modules in Protein Interaction Networks

PubMed Central

Shen, Hong-Bin

2011-01-01

Modern science of networks has brought significant advances to our understanding of complex systems biology. As a representative model of systems biology, Protein Interaction Networks (PINs) are characterized by a remarkable modular structures, reflecting functional associations between their components. Many methods were proposed to capture cohesive modules so that there is a higher density of edges within modules than those across them. Recent studies reveal that cohesively interacting modules of proteins is not a universal organizing principle in PINs, which has opened up new avenues for revisiting functional modules in PINs. In this paper, functional clusters in PINs are found to be able to form unorthodox structures defined as bi-sparse module. In contrast to the traditional cohesive module, the nodes in the bi-sparse module are sparsely connected internally and densely connected with other bi-sparse or cohesive modules. We present a novel protocol called the BinTree Seeking (BTS) for mining both bi-sparse and cohesive modules in PINs based on Edge Density of Module (EDM) and matrix theory. BTS detects modules by depicting links and nodes rather than nodes alone and its derivation procedure is totally performed on adjacency matrix of networks. The number of modules in a PIN can be automatically determined in the proposed BTS approach. BTS is tested on three real PINs and the results demonstrate that functional modules in PINs are not dominantly cohesive but can be sparse. BTS software and the supporting information are available at: www.csbio.sjtu.edu.cn/bioinf/BTS/. PMID:22140454

Function Specifications for the A-7E Function Driver Module.

DTIC Science & Technology

1981-11-27

Computer interface specifications (HEN181). The services and values provided by the Shared Services module are accurately described in the Shared Services Module...None$) FD.7.l.3.1 FD.7.1.7.1 5517a FD.App3 -5 Appendix 3 Event List (Alphabetical) Events Signalled by other Shared Services submodules @F( ABSCI+ip az...the Shared Services and Device Interface modules. Al; Answer this question for each table that appears in the function driver specification being

Extracting a shape function for a signal with intra-wave frequency modulation.

PubMed

Hou, Thomas Y; Shi, Zuoqiang

2016-04-13

In this paper, we develop an effective and robust adaptive time-frequency analysis method for signals with intra-wave frequency modulation. To handle this kind of signals effectively, we generalize our data-driven time-frequency analysis by using a shape function to describe the intra-wave frequency modulation. The idea of using a shape function in time-frequency analysis was first proposed by Wu (Wu 2013 Appl. Comput. Harmon. Anal. 35, 181-199. (doi:10.1016/j.acha.2012.08.008)). A shape function could be any smooth 2π-periodic function. Based on this model, we propose to solve an optimization problem to extract the shape function. By exploring the fact that the shape function is a periodic function with respect to its phase function, we can identify certain low-rank structure of the signal. This low-rank structure enables us to extract the shape function from the signal. Once the shape function is obtained, the instantaneous frequency with intra-wave modulation can be recovered from the shape function. We demonstrate the robustness and efficiency of our method by applying it to several synthetic and real signals. One important observation is that this approach is very stable to noise perturbation. By using the shape function approach, we can capture the intra-wave frequency modulation very well even for noise-polluted signals. In comparison, existing methods such as empirical mode decomposition/ensemble empirical mode decomposition seem to have difficulty in capturing the intra-wave modulation when the signal is polluted by noise. © 2016 The Author(s).

Prior knowledge based mining functional modules from Yeast PPI networks with gene ontology

PubMed Central

2010-01-01

Background In the literature, there are fruitful algorithmic approaches for identification functional modules in protein-protein interactions (PPI) networks. Because of accumulation of large-scale interaction data on multiple organisms and non-recording interaction data in the existing PPI database, it is still emergent to design novel computational techniques that can be able to correctly and scalably analyze interaction data sets. Indeed there are a number of large scale biological data sets providing indirect evidence for protein-protein interaction relationships. Results The main aim of this paper is to present a prior knowledge based mining strategy to identify functional modules from PPI networks with the aid of Gene Ontology. Higher similarity value in Gene Ontology means that two gene products are more functionally related to each other, so it is better to group such gene products into one functional module. We study (i) to encode the functional pairs into the existing PPI networks; and (ii) to use these functional pairs as pairwise constraints to supervise the existing functional module identification algorithms. Topology-based modularity metric and complex annotation in MIPs will be used to evaluate the identified functional modules by these two approaches. Conclusions The experimental results on Yeast PPI networks and GO have shown that the prior knowledge based learning methods perform better than the existing algorithms. PMID:21172053

SU-E-T-97: Dependence Of Optically Stimulated Luminescent Dosimeter (OSLD) Out Of Field Response On Volumetric Modulated Arc Therapy (VMAT) Field Modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ware, S; Clouser, E

2014-06-01

Purpose: To determine the out of field response of Microstar ii OSLDs as a function of field modulation and distance in VMAT plan delivery. This work has potential application in fetal dose monitoring or measurements on cardiac pacemakers Methods: VMAT plans were created in Eclipse and optimized to varying degrees of modulation. Three plans were chosen to represent low, medium and high degrees of modulation (modulation factors as defined by MU/cGy). Plans were delivered to slabs of solid water with dimensions 60cm length, 30cm width, and 10cm height. For each modulation factor, 2 OSLDs were placed at 1cm depth withmore » out of field distances of 1, 2, 3, 5, 8 and 10cm and the plan delivered isocentrically to a depth of 5cm. This technique was repeated for a Farmer Chamber by incrementing the table by the appropriate distance. The charge readings for the Farmer Chamber were converted to dose and the ratios taken as functions of modulation factors and distances out of field Results: Examination of the results as a function of out of field distance shows a trend of increasing OSLD/Farmer Chamber ratios for all modulation factors. The slopes appear to be roughly equivalent for all modulation factors investigated. Results as a function of modulation showed a downward trend for all out of field distances, with the greatest differences seen at 5cm and 8cm Conclusion: This study demonstrates that the response of OSLD dosimeters change as a function of out of field distance and modulation. The differences seen are within the stated accuracy of the system for the out of field distances and modulations investigated. Additional investigation is warranted to see if the OSLD response changes appreciably with longer out of field distances or wider ranges of modulation.« less