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Sample records for adrenal sympathetic nerve

  1. Activation of NTS A2a adenosine receptors differentially resets baroreflex control of renal vs. adrenal sympathetic nerve activity.

    PubMed

    Ichinose, Tomoko K; O'Leary, Donal S; Scislo, Tadeusz J

    2009-04-01

    The role of nucleus of solitary tract (NTS) A(2a) adenosine receptors in baroreflex mechanisms is controversial. Stimulation of these receptors releases glutamate within the NTS and elicits baroreflex-like decreases in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas inhibition of these receptors attenuates HR baroreflex responses. In contrast, stimulation of NTS A(2a) adenosine receptors increases preganglionic adrenal sympathetic nerve activity (pre-ASNA), and the depressor and sympathoinhibitory responses are not markedly affected by sinoaortic denervation and blockade of NTS glutamatergic transmission. To elucidate the role of NTS A(2a) adenosine receptors in baroreflex function, we compared full baroreflex stimulus-response curves for HR, RSNA, and pre-ASNA (intravenous nitroprusside/phenylephrine) before and after bilateral NTS microinjections of selective adenosine A(2a) receptor agonist (CGS-21680; 2.0, 20 pmol/50 nl), selective A(2a) receptor antagonist (ZM-241385; 40 pmol/100 nl), and nonselective A(1) + A(2a) receptor antagonist (8-SPT; 1 nmol/100 nl) in urethane/alpha-chloralose anesthetized rats. Activation of A(2a) receptors decreased the range, upper plateau, and gain of baroreflex-response curves for RSNA, whereas these parameters all increased for pre-ASNA, consistent with direct effects of the agonist on regional sympathetic activity. However, no resetting of baroreflex-response curves along the MAP axis occurred despite the marked decreases in baseline MAP. The antagonists had no marked effects on baseline variables or baroreflex-response functions. We conclude that the activation of NTS A(2a) adenosine receptors differentially alters baroreflex control of HR, RSNA, and pre-ASNA mostly via non-baroreflex mechanism(s), and these receptors have virtually no tonic action on baroreflex control of these sympathetic outputs.

  2. Centrally administered glucagon stimulates sympathetic nerve activity in rat.

    PubMed

    Krzeski, R; Czyzyk-Krzeska, M F; Trzebski, A; Millhorn, D E

    1989-12-18

    The effect of pancreatic glucagon given intravenously, intracerebroventricularly and microinjected into the nucleus of the solitary tract on sympathetic activity in the cervical trunk and adrenal nerve was examined in rat. In each case glucagon caused a relatively long-lasting substantial increase in discharge of both nerves. This finding shows that glucagon can act centrally to stimulate sympathetic activity. The most probable site for the sympathoexcitatory effect of glucagon is the nucleus of the solitary tract. PMID:2598031

  3. 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.

  4. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  5. Seasonal variation in muscle sympathetic nerve activity.

    PubMed

    Cui, Jian; Muller, Matthew D; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

    2015-08-01

    Epidemiologic data suggest there are seasonal variations in the incidence of severe cardiac events with peak levels being evident in the winter. Whether autonomic indices including muscle sympathetic nerve activity (MSNA) vary with season remains unclear. In this report, we tested the hypothesis that resting MSNA varies with the seasons of the year with peak levels evident in the winter. We analyzed the supine resting MSNA in 60 healthy subjects. Each subject was studied during two, three, or four seasons (total 237 visits). MSNA burst rate in the winter (21.0 ± 6.8 burst/min, mean ± SD) was significantly greater than in the summer (13.5 ± 5.8 burst/min, P < 0.001), the spring (17.1 ± 9.0 burst/min, P = 0.03), and the fall (17.9 ± 7.7 burst/min, P = 0.002). There was no significant difference in MSNA for other seasonal comparisons. The results suggest that resting sympathetic nerve activity varies along the seasons, with peak levels evident in the winter. We speculate that the seasonal changes in sympathetic activity may be a contribution to the previously observed seasonal variations in cardiovascular morbidity and mortality. PMID:26265752

  6. Seasonal variation in muscle sympathetic nerve activity

    PubMed Central

    Cui, Jian; Muller, Matthew D; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

    2015-01-01

    Epidemiologic data suggest there are seasonal variations in the incidence of severe cardiac events with peak levels being evident in the winter. Whether autonomic indices including muscle sympathetic nerve activity (MSNA) vary with season remains unclear. In this report, we tested the hypothesis that resting MSNA varies with the seasons of the year with peak levels evident in the winter. We analyzed the supine resting MSNA in 60 healthy subjects. Each subject was studied during two, three, or four seasons (total 237 visits). MSNA burst rate in the winter (21.0 ± 6.8 burst/min, mean ± SD) was significantly greater than in the summer (13.5 ± 5.8 burst/min, P < 0.001), the spring (17.1 ± 9.0 burst/min, P = 0.03), and the fall (17.9 ± 7.7 burst/min, P = 0.002). There was no significant difference in MSNA for other seasonal comparisons. The results suggest that resting sympathetic nerve activity varies along the seasons, with peak levels evident in the winter. We speculate that the seasonal changes in sympathetic activity may be a contribution to the previously observed seasonal variations in cardiovascular morbidity and mortality. PMID:26265752

  7. Hibernating myocardium results in partial sympathetic denervation and nerve sprouting.

    PubMed

    Fernandez, Stanley F; Ovchinnikov, Vladislav; Canty, John M; Fallavollita, James A

    2013-01-15

    Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (-32%, P < 0.001), norepinephrine uptake transport protein (-25%, P = 0.01), and tissue norepinephrine content (-45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors.

  8. [Clinical application of skin sympathetic nerve activity].

    PubMed

    Iwase, Satoshi

    2009-03-01

    Skin sympathetic nerve activity (SSNA) is microneurographically recorded from the skin nerve fascicle in the peripheral nerves. It is characterized by the following features: 1) irregular, pulse asynchronous, burst activity with respiratory variation, 2) burst activity followed by vasoconstriction and/or sweating, 3) elicited by mental stress and arousal stimuli, e.g., sound, pain, electric stimulation, 4) burst with longer duration as compared with sympathetic outflow to muscles, and 5) burst activity following sudden inspiratory action. It comprises vasoconstrictor (VC) and sudomotor(SM) activity, as well as vasodilator (VD) activity. VC and SM discharge independently, whereas VD is the same activity with different neurotransmission. The VC and SM are differentiated by effector response, e.g., laser Doppler flowmetry and skin potential changes. SSNA function in thermoregulation in the human body; however it is also elicited by mental stress. SSNA is the lowest at thermoneutral ambient temperature (approximately 27 degrees C), and is enhanced in the pressence of ambient warm and cool air. The burst amplitude is well-correlated to both skin blood flow reduction rate or sweat rate change. The clinical application of SSNA comprises the following: 1) clarification of sweating phenomenon, 2) clarification and diagnosis of anhidrosis, 3) clarification and diagnosis of hyperhidrosis, 4) clarification of thermoregulatory function and diagnosis of thermoregulatory disorder, 5) clarification of pathophysiology and diagnosis of vascular diseases, e.g., Raynaud and Buerger diseases. 6) clarification of the relation between cognitive function and SSNA and 7) determination of pharmacological effect attributable to change in neuroeffector responses. PMID:19301594

  9. Effects of intranasal cocaine on sympathetic nerve discharge in humans.

    PubMed Central

    Jacobsen, T N; Grayburn, P A; Snyder, R W; Hansen, J; Chavoshan, B; Landau, C; Lange, R A; Hillis, L D; Victor, R G

    1997-01-01

    Cocaine-induced cardiovascular emergencies are mediated by excessive adrenergic stimulation. Animal studies suggest that cocaine not only blocks norepinephrine reuptake peripherally but also inhibits the baroreceptors, thereby reflexively increasing sympathetic nerve discharge. However, the effect of cocaine on sympathetic nerve discharge in humans is unknown. In 12 healthy volunteers, we recorded blood pressure and sympathetic nerve discharge to the skeletal muscle vasculature using intraneural microelectrodes (peroneal nerve) during intranasal cocaine (2 mg/kg, n = 8) or lidocaine (2%, n = 4), an internal local anesthetic control, or intravenous phenylephrine (0.5-2.0 microg/kg, n = 4), an internal sympathomimetic control. Experiments were repeated while minimizing the cocaine-induced rise in blood pressure with intravenous nitroprusside to negate sinoaortic baroreceptor stimulation. After lidocaine, blood pressure and sympathetic nerve discharge were unchanged. After cocaine, blood pressure increased abruptly and remained elevated for 60 min while sympathetic nerve discharge initially was unchanged and then decreased progressively over 60 min to a nadir that was only 2+/-1% of baseline (P < 0.05); however, plasma venous norepinephrine concentrations (n = 5) were unchanged up to 60 min after cocaine. Sympathetic nerve discharge fell more rapidly but to the same nadir when blood pressure was increased similarly with phenylephrine. When the cocaine-induced increase in blood pressure was minimized (nitroprusside), sympathetic nerve discharge did not decrease but rather increased by 2.9 times over baseline (P < 0.05). Baroreflex gain was comparable before and after cocaine. We conclude that in conscious humans the primary effect of intranasal cocaine is to increase sympathetic nerve discharge to the skeletal muscle bed. Furthermore, sinoaortic baroreflexes play a pivotal role in modulating the cocaine-induced sympathetic excitation. The interplay between these

  10. Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure.

    PubMed

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Funakoshi, Hajime; Eckhart, Andrea D; Koch, Walter J

    2007-03-01

    Cardiac overstimulation by the sympathetic nervous system (SNS) is a salient characteristic of heart failure, reflected by elevated circulating levels of catecholamines. The success of beta-adrenergic receptor (betaAR) antagonists in heart failure argues for SNS hyperactivity being pathogenic; however, sympatholytic agents targeting alpha2AR-mediated catecholamine inhibition have been unsuccessful. By investigating adrenal adrenergic receptor signaling in heart failure models, we found molecular mechanisms to explain the failure of sympatholytic agents and discovered a new strategy to lower SNS activity. During heart failure, there is substantial alpha2AR dysregulation in the adrenal gland, triggered by increased expression and activity of G protein-coupled receptor kinase 2 (GRK2). Adrenal gland-specific GRK2 inhibition reversed alpha2AR dysregulation in heart failure, resulting in lowered plasma catecholamine levels, improved cardiac betaAR signaling and function, and increased sympatholytic efficacy of a alpha2AR agonist. This is the first demonstration, to our knowledge, of a molecular mechanism for SNS hyperactivity in heart failure, and our study identifies adrenal GRK2 activity as a new sympatholytic target.

  11. Role of sympathetic nerve activity in the process of fainting

    PubMed Central

    Iwase, Satoshi; Nishimura, Naoki; Mano, Tadaaki

    2014-01-01

    Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression is here described with two types of sympathetic change. Simultaneous recordings of microneurographically-recorded muscle sympathetic nerve activity (MSNA) and continuous and noninvasive blood pressure measurement has disclosed what is going on during the course of syncope progression. For vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. Vasovagal syncope is characterized by sympathoexcitation, followed by vagal overcoming via the Bezold-Jarisch reflex. Orthostatic syncope is caused by response failure or a lack of sympathetic nerve activity to the orthostatic challenge, followed by fluid shift and subsequent low cerebral perfusion. Four causes are considered for the compensatory failure that triggers orthostatic syncope: hypovolemia, increased pooling in the lower body, failure to activate sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions have been described from the perspectives of (1) exaggerated sympathoexcitation and (2) failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control cardiovascular function, and its failure results in syncope; however, responses of the system obtained by microneurographically-recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism. PMID:25309444

  12. Adrenal medullary ganglion neurons project into the splanchnic nerve.

    PubMed

    Dagerlind, A; Pelto-Huikko, M; Diez, M; Hökfelt, T

    1995-12-01

    Retrograde tract-tracing was used to study the projections of adrenal medullary ganglion neurons. The splanchnic nerve was cut close to the suprarenal ganglia and the retrograde tracer FluoroGold was applied at the site of nerve transection. Groups of adrenal medullary ganglion neurons exhibited FlurorGold- or Fast Blue-induced fluorescence restricted to the perikarya. Using immunohistochemistry most retrogradely labelled ganglion neurons showed immunoreactivity for neuropeptide Y. In addition, after splanchnicotomy most ganglion neurons expressed galanin and galanin message-associated peptide immunoreactivities which could not be observed in control adrenals. Taken together, the present results strongly indicate that adrenal medullary ganglion neurons project back into the splanchnic nerve perhaps representing feedback system modulating the preganglionic innervation of the adrenal gland.

  13. Involvement of the orexin system in sympathetic nerve regulation.

    PubMed

    Murakami, Manabu; Ohba, Takayoshi; Kushikata, Testuya; Niwa, Hidetoshi; Kurose, Akira; Imaizumi, Tadaatsu; Watanabe, Hiroyuki; Yanagisawa, Teruyuki; Nakaji, Shigeyuki; Ono, Kyoichi; Hirota, Kazuyoshi

    2015-05-15

    Orexin, also known as hypocretin, is a secreted neuropeptide implicated in the regulation of sleep and food intake. In the present study, we examined the importance of orexin in regulation of the sympathetic nervous system using an orexin/ataxin-3 transgenic (OXTg) rat, which has a minimal number of orexin neurons. RT-PCR analysis identified expression of prepro-orexin and orexin receptor-1 (OX1R) in the superior cervical ganglion (SCG), and expression of another receptor (OX2R) was marginal in the wild-type rat. The orexin/ataxin-3 transgenic rat showed increased expression of OX1R and OX2R, whereas expression of prepro-orexin was undetectable, suggesting a compensatory increase in both receptors. In the ECG recording (R-R interval), orexin/ataxin-3 transgenic rats showed decreased responsiveness to the β-adrenergic blocker propranolol. Furthermore, OXTg rats had deteriorated R-R interval regulation, indicating involvement of the orexin system in sympathetic nerve regulation. This was accompanied by decreased baroreflex and responsiveness to β-adrenergic blocker in blood pressure recording, also suggesting involvement of the orexin system in sympathetic nerve regulation. Histological examination revealed hypotrophic changes in the transgenic heart, suggesting involvement of the orexin system in cardiac development. Taken together, our present results indicate involvement of the orexin system in sympathetic nerve control.

  14. Reflex control of inflammation by sympathetic nerves, not the vagus.

    PubMed

    Martelli, D; Yao, S T; McKinley, M J; McAllen, R M

    2014-04-01

    We investigated a neural reflex that controls the strength of inflammatory responses to immune challenge - the inflammatory reflex. In anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 60 μg kg(-1)), we found strong increases in plasma levels of the key inflammatory mediator tumour necrosis factor α (TNFα) 90 min later. Those levels were unaffected by previous bilateral cervical vagotomy, but were enhanced approximately 5-fold if the greater splanchnic sympathetic nerves had been cut. Sham surgery had no effect, and plasma corticosterone levels were unaffected by nerve sections, so could not explain this result. Electrophysiological recordings demonstrated that efferent neural activity in the splanchnic nerve and its splenic branch was strongly increased by LPS treatment. Splenic nerve activity was dependent on inputs from the splanchnic nerves: vagotomy had no effect on the activity in either nerve. Together, these data demonstrate that immune challenge with this dose of LPS activates a neural reflex that is powerful enough to cause an 80% suppression of the acute systemic inflammatory response. The efferent arm of this reflex is in the splanchnic sympathetic nerves, not the vagi as previously proposed. As with other physiological responses to immune challenge, the afferent pathway is presumptively humoral: the present data show that vagal afferents play no measurable part. Because inflammation sits at the gateway to immune responses, this reflex could play an important role in immune function as well as inflammatory diseases.

  15. Reflex control of inflammation by sympathetic nerves, not the vagus

    PubMed Central

    Martelli, D; Yao, S T; McKinley, M J; McAllen, R M

    2014-01-01

    We investigated a neural reflex that controls the strength of inflammatory responses to immune challenge – the inflammatory reflex. In anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 60 μg kg−1), we found strong increases in plasma levels of the key inflammatory mediator tumour necrosis factor α (TNFα) 90 min later. Those levels were unaffected by previous bilateral cervical vagotomy, but were enhanced approximately 5-fold if the greater splanchnic sympathetic nerves had been cut. Sham surgery had no effect, and plasma corticosterone levels were unaffected by nerve sections, so could not explain this result. Electrophysiological recordings demonstrated that efferent neural activity in the splanchnic nerve and its splenic branch was strongly increased by LPS treatment. Splenic nerve activity was dependent on inputs from the splanchnic nerves: vagotomy had no effect on the activity in either nerve. Together, these data demonstrate that immune challenge with this dose of LPS activates a neural reflex that is powerful enough to cause an 80% suppression of the acute systemic inflammatory response. The efferent arm of this reflex is in the splanchnic sympathetic nerves, not the vagi as previously proposed. As with other physiological responses to immune challenge, the afferent pathway is presumptively humoral: the present data show that vagal afferents play no measurable part. Because inflammation sits at the gateway to immune responses, this reflex could play an important role in immune function as well as inflammatory diseases. PMID:24421357

  16. Regulation of the renal sympathetic nerves in heart failure

    PubMed Central

    Ramchandra, Rohit; Barrett, Carolyn J.

    2015-01-01

    Heart failure (HF) is a serious debilitating condition with poor survival rates and an increasing level of prevalence. HF is associated with an increase in renal norepinephrine (NE) spillover, which is an independent predictor of mortality in HF patients. The excessive sympatho-excitation that is a hallmark of HF has long-term effects that contribute to disease progression. An increase in directly recorded renal sympathetic nerve activity (RSNA) has also been recorded in animal models of HF. This review will focus on the mechanisms controlling sympathetic nerve activity (SNA) to the kidney during normal conditions and alterations in these mechanisms during HF. In particular the roles of afferent reflexes and central mechanisms will be discussed. PMID:26388778

  17. Thoracic sympathetic nerve reconstruction for compensatory hyperhidrosis: the Melbourne technique

    PubMed Central

    Hensman, Chris; Leong, James

    2014-01-01

    Background Compensatory hyperhidrosis (CH) is a potential complication following endoscopic thoracic sympathectomy (ETS) in the management of primary hyperhidrosis. CH is considered a permanent condition with significant psychosocial impacts but with few treatment options. Various reversal surgical techniques, aimed at reconstituting sympathetic pathways, have been developed but results have been inconsistent. Objective We present two case reports of a novel technique of reversal surgery, the Melbourne technique, which was employed to treat severe CH that developed within 3-5 months following ETS. Both patients were followed-up to 8 years. Methods The Melbourne technique employs an endoscopic approach to expose previously sympathectomized or sympathotomized thoracic sympathetic chains. In these two cases it was performed on the right side only. Instead of an interpositional nerve graft, an autogenous vein graft was simultaneously harvested and used as a nerve conduit to bridge the secondary nerve defect after neuroma excision. Long-term outcomes were assessed using the dermatology life quality index (DLQI) and the quality of life (QoL) questionnaires, which are validated for hyperhidrosis. Results In both cases, patients reported postoperative improvements in QoL scores. However, the improvement was more marked in one case compared with the other. There were no significant immediate and long-term postoperative complications. Conclusions The Melbourne technique shows promise as an alternative to interpositional nerve grafts or nerve transfers employed in other endoscopic reversal surgeries for CH. PMID:25333020

  18. Attenuated sympathetic nerve responses after 24 hours of bed rest

    NASA Technical Reports Server (NTRS)

    Khan, Mazhar H.; Kunselman, Allen R.; Leuenberger, Urs A.; Davidson, William R Jr; Ray, Chester A.; Gray, Kristen S.; Hogeman, Cynthia S.; Sinoway, Lawrence I.

    2002-01-01

    Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.

  19. Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension.

    PubMed

    Chen, W; Leo, S; Weng, C; Yang, X; Wu, Y; Tang, X

    2015-04-01

    Excessive renal sympathetic nerve activation may be one of the mechanisms underlying obesity-related hypertension. Impaired baroreflex sensitivity, adipokine disorders-such as leptin, adiponectin, and resistin-activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance, and renal sodium retention present in obesity increase renal sympathetic nerve activity, thus contributing to the development of hypertension. Renal sympathetic denervation reduces both renal sympathetic activity and blood pressure in patients with obesity-related hypertension.

  20. Effects of leptin on sympathetic nerve activity in conscious mice

    PubMed Central

    Morgan, Donald A; Despas, Fabien; Rahmouni, Kamal

    2015-01-01

    The adipocyte-derived hormone, leptin, has emerged as an important regulator of regional sympathetic nerve activity (SNA) with pathophysiological implications in obesity. Genetically engineered mice are useful to understand the molecular pathways underlying the SNA responses evoked by leptin. However, so far the effect of leptin on direct SNA in mice has been studied under general anesthesia. Here, we examined the sympathetic responses evoked by leptin in conscious mice. Mice were instrumented, under ketamine/xylazine anesthesia, with renal or lumbar SNA recordings using a thin (40 gauge) bipolar platinum–iridium wire. The electrodes were exteriorized at the nape of the neck and mice were allowed (5 h) to recover from anesthesia. Interestingly, the reflex increases in renal and lumbar SNA caused by sodium nitroprusside (SNP)-induced hypotension was higher in the conscious phase versus the anesthetized state, whereas the increase in both renal and lumbar SNA evoked by leptin did not differ between anesthetized or conscious mice. Next, we assessed whether isoflurane anesthesia would yield a better outcome. Again, the SNP-induced increase in renal SNA and baroreceptor-renal SNA reflex were significantly elevated in the conscious states relative to isoflurane-anesthetized phase, but the renal SNA response induced by leptin in the conscious states were qualitatively comparable to those evoked above. Thus, despite improvement in sympathetic reflexes in conscious mice the sympathetic responses evoked by leptin mimic those induced during anesthesia. PMID:26381017

  1. Effect of morphine on sympathetic nerve activity in humans

    NASA Technical Reports Server (NTRS)

    Carter, Jason R.; Sauder, Charity L.; Ray, Chester A.

    2002-01-01

    There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.

  2. Effects of leptin on sympathetic nerve activity in conscious mice.

    PubMed

    Morgan, Donald A; Despas, Fabien; Rahmouni, Kamal

    2015-09-01

    The adipocyte-derived hormone, leptin, has emerged as an important regulator of regional sympathetic nerve activity (SNA) with pathophysiological implications in obesity. Genetically engineered mice are useful to understand the molecular pathways underlying the SNA responses evoked by leptin. However, so far the effect of leptin on direct SNA in mice has been studied under general anesthesia. Here, we examined the sympathetic responses evoked by leptin in conscious mice. Mice were instrumented, under ketamine/xylazine anesthesia, with renal or lumbar SNA recordings using a thin (40 gauge) bipolar platinum-iridium wire. The electrodes were exteriorized at the nape of the neck and mice were allowed (5 h) to recover from anesthesia. Interestingly, the reflex increases in renal and lumbar SNA caused by sodium nitroprusside (SNP)-induced hypotension was higher in the conscious phase versus the anesthetized state, whereas the increase in both renal and lumbar SNA evoked by leptin did not differ between anesthetized or conscious mice. Next, we assessed whether isoflurane anesthesia would yield a better outcome. Again, the SNP-induced increase in renal SNA and baroreceptor-renal SNA reflex were significantly elevated in the conscious states relative to isoflurane-anesthetized phase, but the renal SNA response induced by leptin in the conscious states were qualitatively comparable to those evoked above. Thus, despite improvement in sympathetic reflexes in conscious mice the sympathetic responses evoked by leptin mimic those induced during anesthesia.

  3. Sympathetic Nerve Activity and Simulated Diving in Healthy Humans

    PubMed Central

    Shamsuzzaman, Abu; Ackerman, Michael J.; Kuniyoshi, Fatima Sert; Accurso, Valentina; Davison, Diane; Amin, Raouf S.; Somers, Virend K.

    2014-01-01

    The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea and congenital long QT syndrome. PMID:24368150

  4. Sympathetic nerve activity and simulated diving in healthy humans.

    PubMed

    Shamsuzzaman, Abu; Ackerman, Michael J; Kuniyoshi, Fatima Sert; Accurso, Valentina; Davison, Diane; Amin, Raouf S; Somers, Virend K

    2014-04-01

    The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.

  5. Gross anatomical study of the sympathetic cardiac nerves in the house musk shrew (Suncus murinus).

    PubMed

    Tanaka, Ai; Tanaka, Shigenori; Miyamoto, Kensaku; Yi, Shuang-Qin; Nakatani, Toshio

    2007-05-01

    The sympathetic cardiac nerves originating from the cervical and upper thoracic sympathetic ganglia in the house musk shrew (Suncus murinus) were examined using macroscopic and whole-mount immunohistochemical methods. Based on the results, the nerves were macroscopically classified into the following three groups: nerves innervating the cervical sympathetic ganglia mainly to the arterial porta of the heart; nerves supplying the stellate and thoracic sympathetic ganglia at the level of T2-T5 or T6 for both the arterial and venous portae of the heart; and nerves innervating the thoracic sympathetic ganglia at the level of T4-T9 to the esophagus and lung and then the heart via the blood vessels within the mediastinal pleura. These findings in the house musk shrew suggest a possible primitive morphological pattern of the cervical and thoracic sympathetic nervous system that may be related to those in other mammals, including humans. PMID:17393537

  6. Asian women have attenuated sympathetic activation but enhanced renal-adrenal responses during pregnancy compared to Caucasian women.

    PubMed

    Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S; Shibata, Shigeki; Parker, Rosemary S; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2015-03-01

    Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal-adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32-36 weeks) pregnancy, and post-partum (6-10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min(-1) and 16 ± 5 vs. 30 ± 3 bursts min(-1) in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min(-1) at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal-adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy. PMID:25545472

  7. The innervation of the adrenal gland. IV. The source of pre- and postganglionic nerve fibres to the guinea-pig adrenal gland.

    PubMed

    Parker, T L; Mohamed, A A; Coupland, R E

    1990-10-01

    The pre- and postganglionic sympathetic innervation of the guinea-pig adrenal medulla was investigated using the retrograde neuronal tracers Fast Blue and WGA-HRP. Labelled preganglionic cell bodies were located in the intermediolateral horn of spinal segments T3-L2, the majority (73.9%) were found between T6-T12 representing 70.2% of the total number of labelled cells; the segment T10 contained the largest number of labelled neurons. Labelled postganglionic cell bodies were found in the paravertebral ganglia between vertebral levels T3-T12 (representing 22.6% of the total labelled neurons), the maximum number was found at T10. In addition, labelled neurons were found in the suprarenal ganglion (representing 7.2%). No labelled cells were found in the coeliac ganglia. The labelled neurons were found ipsilateral to the site of injection into the left adrenal gland. It is concluded that the guinea-pig adrenal gland receives both a pre- and a significant postganglionic sympathetic innervation. The destination of these nerve fibres within the adrenal gland has yet to be determined.

  8. CO2 asphyxia increases plasma norepinephrine in rats via sympathetic nerves.

    PubMed

    Borovsky, V; Herman, M; Dunphy, G; Caplea, A; Ely, D

    1998-01-01

    The objective of this study was to determine whether the plasma norepinephrine (NE) increase in rats exposed to CO2 asphyxia was due to adrenal gland release or sympathetic nerve ending (SNS) release. Plasma NE was measured by high-performance liquid chromatography in hypertensive and normotensive rats using the following protocol: control session, CO2 exposure, N2 exposure, reserpine + CO2, and adrenalectomy + CO2. Four strains of male and female rats were used: spontaneously hypertensive rats, Wistar-Kyoto rats, and two congenic strains with different Y chromosomes. The same rats were used throughout the experiment (n = 80). Blood pressure measured by aortic telemetry increased approximately 50-60 mmHg in response to CO2 in all strains. CO2 increased NE 6-10x in all strains and both genders. N2 produced a significant increase in NE (73% of CO2 response). Reserpine significantly decreased (67%) plasma NE after CO2. Adrenalectomy did not significantly reduce the NE response to CO2. In conclusion, the increase in plasma NE after CO2 was associated with SNS release and not adrenal medullary release, was mainly due to hypoxia, and was not a specific response to CO2.

  9. Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

    PubMed Central

    Lechin, Fuad; van der Dijs, Bertha; Pardey-Maldonado, Betty; Rivera, Jairo E; Baez, Scarlet; Lechin, Marcel E

    2010-01-01

    Objective The aim of our study was to determine the central and peripheral autonomic nervous system profiles underlying anorexia nervosa (AN) syndrome, given that affected patients present with the opposite clinical profile to that seen in the hyperinsulinism syndrome. Design We measured blood pressure and heart rate, as well as circulating neurotransmitters (noradrenaline, adrenaline, dopamine, plasma serotonin, and platelet serotonin), using high-performance liquid chromatography with electrochemical detection, during supine resting, one minute of orthostasis, and after five minutes of exercise. In total, 22 AN patients (12 binge-eating/purging type and 10 restricting type) and age-, gender-, and race-matched controls (70 ± 10.1% versus 98 ± 3.0% of ideal body weight) were recruited. Results We found that patients with AN had adrenal sympathetic overactivity and neural sympathetic underactivity, demonstrated by a predominance of circulating adrenaline over noradrenaline levels, not only during the supine resting state (52 ± 2 versus 29 ± 1 pg/mL) but also during orthostasis (67 ± 3 versus 32 ± 2 pg/mL, P < 0.05) and after exercise challenge (84 ± 4 versus 30 ± 3 pg/mL, P < 0.01). Conclusion Considering that this peripheral autonomic nervous system disorder depends on the absolute predominance of adrenomedullary C1 adrenergic nuclei over A5 noradrenergic pontine nucleus, let us ratify the abovementioned findings. The AN syndrome depends on the predominance of overwhelming adrenal sympathetic activity over neural sympathetic activity. This combined central and autonomic nervous system profile contrasts with that registered in patients affected by hyperinsulinism, hypoglycemia, and bulimia syndrome which depends on the absolute predominance of neural sympathetic activity. PMID:21437100

  10. Respiratory-related discharge pattern of sympathetic nerve activity in the spontaneously hypertensive rat.

    PubMed Central

    Czyzyk-Krzeska, M F; Trzebski, A

    1990-01-01

    1. Synchronization of spontaneous sympathetic discharge during the respiratory cycle was studied in the cervical and renal nerves of vagotomized, normotensive Wistar-Kyoto rats (WKYs) and age-matched spontaneously hypertensive rats (SHRs). Phrenic nerve discharge was used as an index of central inspiratory activity. 2. In normotensive Wistar-Kyoto rats depression of sympathetic activity appeared at the onset of inspiration reaching a minimum at mid-inspiration. Peak maximal sympathetic discharge corresponded to postinspiratory phase; a second increase sometimes appeared in late expiration. Variations of respiratory frequency over wide range of experimental conditions by hypoxia, hyperoxia, hyper- or hypocapnia and transection of carotid sinus nerves did not affect this pattern. 3. In SHRs the respiratory-phase-related timing of sympathetic discharge was variable. In normoxia, the maximal sympathetic activity occurred in late inspiration, preceded by short depression at early inspiration and followed by postinspiratory depression. A second increase in sympathetic activity was observed in mid-expiration. 4. The pattern of respiratory phase modulated sympathetic activity in SHRs was altered by hypoxic stimulation of the peripheral chemoreceptors. The early inspiratory depression of sympathetic activity was substantially prolonged and the maximal sympathetic discharge was shifted from inspiration to early expiration. This effect was abolished after carotid sinus nerves had been cut. 5. Hypercapnic stimulation of central chemoreceptors in SHRs with carotid sinus nerves cut did not influence the timing of the sympathetic activity in relation to the respiratory phase, though the magnitude of rhythmical sympathetic discharges was increased. 6. We discuss the possibility that altered synchronization between central respiratory drive and sympathetic neuronal system may contribute to the neurogenic mechanisms of arterial hypertension in SHRs. PMID:2231403

  11. Relationship between sympathetic nerve sprouting and repolarization dispersion at peri-infarct zone after myocardial infarction.

    PubMed

    Jiang, Hong; Lu, Zhibing; Yu, Ying; Zhao, Dongdong; Yang, Bo; Huang, Congxin

    2007-07-31

    Sympathetic nerve sprouting is thought to contribute to sudden cardiac death (SCD) in chronic myocardial infarction (MI). However, the mechanisms remain unclear. This study investigated the relationship between sympathetic nerve sprouting and repolarization dispersion at peri-infarct zones after MI. Thirty adult New Zealand White rabbits underwent coronary artery ligation (MI group: n=20) or sham operation (SO group: n=10). Eight weeks after surgery, transmural dispersion of repolarization (TDR) was examined at the peri-infarct zones in MI group and corresponding zones in the SO group at baseline and during sympathetic nerve stimulation. Sympathetic nerve sprouting was detected by immunocytochemical staining using anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. The results demonstrated that TDR was significantly larger at peri-infarct zones in MI group than the corresponding zone in SO group at baseline or during sympathetic nerve stimulation. The densities of both GAP43- and TH-positive nerves were significantly higher at peri-infarct zones in infracted hearts than the corresponding zones in control hearts (both p<0.01). In the MI group, the density of GAP43- or TH-positive nerves at peri-infarct zones had a significantly positive correlation with the TDR or DeltaTDR (change in TDR) at baseline as well as with sympathetic nerve stimulation (p<0.05 for all). These results suggested that sympathetic nerve sprouting is more pronounced and heterogeneous at peri-infarct zones at 8 weeks after MI. The excessive sprouting of sympathetic nerves increases local ventricular TDR, which may be a potential mechanism for SCD in chronic MI.

  12. Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

    NASA Technical Reports Server (NTRS)

    Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

    1996-01-01

    OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular

  13. The proportions of sympathetic postganglionic and unmyelinated afferent axons in normal and regenerated cat sural nerves.

    PubMed

    Lisney, S J

    1988-03-01

    Electrophysiological experiments have been carried out to see if the proportions of sympathetic postganglionic and unmyelinated afferent axons in a cutaneous nerve were changed after injury and regeneration. It seemed possible that an alteration in the relative numbers of the two groups of axons could contribute to the aetiology of reflex sympathetic dystrophy, but the experiments provided no evidence for such a change. There were, however, signs of a decrease in axon numbers in the regenerated nerves. PMID:3379252

  14. Regulation of muscle sympathetic nerve activity after bed rest deconditioning

    NASA Technical Reports Server (NTRS)

    Pawelczyk, J. A.; Zuckerman, J. H.; Blomqvist, C. G.; Levine, B. D.

    2001-01-01

    Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.

  15. A Central Role for Sympathetic Nerves in Herpes Stromal Keratitis in Mice

    PubMed Central

    Yun, Hongmin; Lathrop, Kira L.; Hendricks, Robert L.

    2016-01-01

    Purpose Herpes simplex virus type 1 (HSV-1) is a neurotrophic virus that can cause herpes stromal keratitis (HSK), a severe corneal inflammation that can lead to corneal scarring and blindness. This study identified neurologic changes that occur in HSV-1–infected corneas and related them to HSV-1–induced immunopathology. Methods Corneas of BALB/c and C57BL/6 mice were infected with HSV-1 strains that induce HSK. Changes in sensory nerves were identified by immunofluorescence staining of sensory and sympathetic nerves for substance P (SP) and tyrosine hydroxylase (TH), respectively, and confocal microscopic examination. Some mice received superior cervical ganglionectomy (SCGx) to eliminate sympathetic nerves from the cornea. Results Normal corneas exclusively expressed sensory nerves that entered the stroma as large nerve stalks, branched to form a plexus at the epithelial/stromal interface, and extended termini into the epithelium. These nerves completely retracted from the infected cornea and were replaced by sympathetic nerves that sprouted extensively to hyperinnervate the corneal stroma but failed to form a plexus or extend termini into the epithelium. The hyperinnervating nerves expressed the sympathetic nerve marker TH and their invasion was blocked by performing SCGx. Moreover, the corneal opacity and neovascularization that normally characterizes HSK in this mouse model were largely abrogated by SCGx. Sensory nerves reinnervated infected corneas following SCGx, reformed a nerve plexus, and extended termini into the epithelium resulting in recovery of corneal sensitivity. Conclusions Sympathetic nerves have a central role in HSK in mice, preventing reinnervation by sensory nerves and promoting severe and persistent corneal inflammation. PMID:27070108

  16. Asian women have attenuated sympathetic activation but enhanced renal–adrenal responses during pregnancy compared to Caucasian women

    PubMed Central

    Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S; Shibata, Shigeki; Parker, Rosemary S; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2015-01-01

    Abstract Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal–adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32–36 weeks) pregnancy, and post-partum (6–10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min−1 and 16 ± 5 vs. 30 ± 3 bursts min−1 in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min−1 at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal–adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy. Key points Asian women have a lower prevalence of hypertensive disorders of pregnancy than Caucasian

  17. Expression of ghrelin in human fetal adrenal glands and paraadrenal nerve ganglions.

    PubMed

    Obara-Moszyńska, Monika; Kedzia, Andrzej; Chmielnicka-Kopaczyk, Maria

    2009-01-01

    The aim of this paper was assessment of location, expression and role of ghrelin in the development and maturation of human fetal adrenal glands and paraadrenal nerve ganglions. Immunohistochemistry was used. The strongest expression of ghrelin was detected in the fetal zone of the adrenal glands, in the neuroepithelial cells of the medullar portion of the adrenals and in few nerve ganglion cells. Ghrelin takes part in molecular processes of proliferation and maturation, and does not influence on steroidogenesis.

  18. Studies on the Release of Renin by Direct and Reflex Activation of Renal Sympathetic Nerves.

    ERIC Educational Resources Information Center

    Donald, David E.

    1979-01-01

    Presents data on release of renin during direct and indirect stimulation of renal nerves. Conclusions show that renin release is influenced by change in activity of carotid and cardiopulmonary baroreceptor systems, and excitation of discrete areas of brain and hypothalamus by changes in renal sympathetic nerve. (Author/SA)

  19. Myocardial Infarction Causes Transient Cholinergic Transdifferentiation of Cardiac Sympathetic Nerves via gp130

    PubMed Central

    Olivas, Antoinette; Gardner, Ryan T.; Wang, Lianguo; Ripplinger, Crystal M.; Woodward, William R.

    2016-01-01

    Sympathetic and parasympathetic control of the heart is a classic example of norepinephrine (NE) and acetylcholine (ACh) triggering opposing actions. Sympathetic NE increases heart rate and contractility through activation of β receptors, whereas parasympathetic ACh slows the heart through muscarinic receptors. Sympathetic neurons can undergo a developmental transition from production of NE to ACh and we provide evidence that mouse cardiac sympathetic nerves transiently produce ACh after myocardial infarction (MI). ACh levels increased in viable heart tissue 10–14 d after MI, returning to control levels at 21 d, whereas NE levels were stable. At the same time, the genes required for ACh synthesis increased in stellate ganglia, which contain most of the sympathetic neurons projecting to the heart. Immunohistochemistry 14 d after MI revealed choline acetyltransferase (ChAT) in stellate sympathetic neurons and vesicular ACh transporter immunoreactivity in tyrosine hydroxylase-positive cardiac sympathetic fibers. Finally, selective deletion of the ChAT gene from adult sympathetic neurons prevented the infarction-induced increase in cardiac ACh. Deletion of the gp130 cytokine receptor from sympathetic neurons prevented the induction of cholinergic genes after MI, suggesting that inflammatory cytokines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons. Ex vivo experiments examining the effect of NE and ACh on rabbit cardiac action potential duration revealed that ACh blunted both the NE-stimulated decrease in cardiac action potential duration and increase in myocyte calcium transients. This raises the possibility that sympathetic co-release of ACh and NE may impair adaptation to high heart rates and increase arrhythmia susceptibility. SIGNIFICANCE STATEMENT Sympathetic neurons normally make norepinephrine (NE), which increases heart rate and the contractility of cardiac myocytes. We found that, after myocardial infarction, the

  20. Human sympathetic nerve biology: parallel influences of stress and epigenetics in essential hypertension and panic disorder.

    PubMed

    Esler, Murray; Eikelis, Nina; Schlaich, Markus; Lambert, Gavin; Alvarenga, Marlies; Kaye, David; El-Osta, Assam; Guo, Ling; Barton, David; Pier, Ciaran; Brenchley, Celia; Dawood, Tye; Jennings, Garry; Lambert, Elisabeth

    2008-12-01

    Patients with panic disorder provide a clinical model of stress. On a "good day," free from a panic attack, they show persistent stress-related changes in sympathetic nerve biology, including abnormal sympathetic nerve single-fiber firing ("salvos" of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N-methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress--a disputed proposition--we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single-fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene

  1. Characteristics of sympathetic nerve activity in the rat sciatic nerve in response to microstimulation in a sympathetic fascicle in the contralateral side.

    PubMed

    Sato, Daisuke; Shiwaku, Yutaka; Nakamura, Ryoichi; Koizumi, Shuntaro; Feng, Zhonggang; Kusunoki, Masataka; Nakamura, Takao

    2013-01-01

    Microneurography is used for the monitor of various peripheral nerve activities. We recently reported that the electrical stimulation of peripheral sympathetic nerve fascicle via the microelectrode, i.e., microstimulation, temporarily reduced the blood glucose level in rats in case that the stimulation intensity was set high enough to induce small muscle contraction. However, the nature of microstimulation has little been clarified yet. Therefore, in the present study, we first detected sympathetic nerve signal microneurographically in the bilateral sciatic nerves of rats, and one of the microelectrodes was used for the microstimulation (0.25 ms-width pulse train at a rate of 1 Hz) while sympathetic nerve activity (SNA) was recorded in the contralateral side as a parameter of systemic sympathetic effects. The SNA, expressed as action potential rate, was transiently increased 150 ms after each stimulation pulse in case that the stimulation intensity was set not less than -0.1 V from the contraction threshold (around 0.32 V). To confirm that the increase was not caused by the activation of low threshold, thick fibers such as motor nerves in the vicinity of the microelectrode tip, next, a bipolar hook electrode, instead of the microelectrode, was then used in the stimulation side. As a result, the above-mentioned, transient increase in SNA was not observed any more in the contralateral side. These results suggest that systemic SNA could be enhanced with lower stimulation intensity than that inducing muscle contraction, and that thicker fibers may little affect the increase in the contralateral SNA. PMID:24111188

  2. Resistin, an Adipokine with Non-Generalized Actions on Sympathetic Nerve Activity

    PubMed Central

    Badoer, Emilio; Kosari, Samin; Stebbing, Martin J.

    2015-01-01

    The World Health Organization has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognized as a chronic, low level inflammatory condition, and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well-known adipokine released from fat tissue is leptin. The adipokine, resistin, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other's actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity. PMID:26617526

  3. Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure.

    PubMed

    Kimura, Kensuke; Kanazawa, Hideaki; Ieda, Masaki; Kawaguchi-Manabe, Haruko; Miyake, Yoshiko; Yagi, Takashi; Arai, Takahide; Sano, Motoaki; Fukuda, Keiichi

    2010-08-25

    In severe congestive heart failure (CHF), sympathetic overactivity correlates with the exacerbation of cardiac performance. To test the hypothesis that the cardiac sympathetic nerve density dramatically changes with the acceleration of circulating norepinephrine (NE) concentration, we investigated the temporal association of nerve growth factor (NGF) expression in the heart and cardiac sympathetic nerve density during the development of CHF in the continuous NE-infused rats. The animals were analyzed at 0-, 1-, 3-, 7-, 14-, and 28-day after implantation of osmotic pump at a rate of 0.05 mg/kg/hr. The cardiac performance was temporally facilitated in NE-exposed rats at 3-day in accordance with the sympathetic hyper-innervation induced by the augmentation of NGF mRNA expression in the heart. In NE-treated rats, left ventricular end-diastolic pressure was significantly increased after 7-day and marked left ventricular hypertrophy and systemic fluid retention were observed at 28-day. CHF-induced sympathetic overactivity further increased plasma NE concentration in NE-treated rats and finally reached to 16.1+/-5.6 ng/ml at 28-day (control level was 0.39+/-0.1 ng/ml, p<0.01). In the decompensated CHF rats at 28-day, the NGF mRNA expression was conspicuously reduced concomitant with the obvious nerve fiber loss confirmed by the immunostaining of nerve axonal marker, PGP9.5 and sympathetic neuron marker, tyrosine hydroxylase. This resulted in the attenuated tissue NE contents and the exacerbating cardiac performance. The cardiac sympathetic fiber loss was also confirmed in NE-exposed DBH (dopamine beta-hydroxylase)-Cre/Floxed-EGFP (enhanced green fluorescent protein) mice with severe CHF, in which sympathetic nerve could be traced by EGFP. Our results suggest that the cardiac sympathetic nerve density is strictly regulated by the NGF expression in the heart and long-exposure of high plasma NE concentration caused myocardial NGF reduction, following sympathetic fiber loss

  4. Sympathetic modulation of sensory nerve activity with age: human and rodent skin models.

    PubMed

    Khalil, Z; LeVasseur, S; Merhi, M; Helme, R D

    1997-11-01

    1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing. 2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses. 3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model. 4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model. 5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low-frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency of stimulation.

  5. What can we learn about neural control of the cardiovascular system by studying rhythms in sympathetic nerve activity?

    PubMed

    Barman, Susan M

    2016-05-01

    Since the first recordings of sympathetic nerve activity in the 1930s, it was very clear that the activity was organized into bursts synchronized to the respiratory and cardiac cycles. Since the early studies, evidence has accumulated showing that sympathetic neural networks are quite complex and generate a variety of periodicities that range between ~0.04 and 10Hz, depending on the physiological state, type of nerve being analyzed, age of the subject, and the species. Despite the ubiquity of sympathetic rhythms, many investigators have failed to consider this oscillatory characteristic of sympathetic nerve activity and instead rely on simply quantifying changes in the level of activity to make decisions about the role of the sympathetic nervous system in mediating certain behaviors. This review highlights work that shows the importance of including an assessment of the frequency characteristics of sympathetic nerve activity. PMID:25681532

  6. Baroreflex modulation of muscle sympathetic nerve activity at rest does not differ between morning and afternoon

    PubMed Central

    Hissen, Sarah L.; Macefield, Vaughan G.; Brown, Rachael; Witter, Trevor; Taylor, Chloe E.

    2015-01-01

    The incidence of cardiovascular events is significantly higher in the morning than other times of day. This has previously been associated with poor blood pressure control via the cardiac baroreflex. However, it is not known whether diurnal variation exists in vascular sympathetic baroreflex function, in which blood pressure is regulated via muscle sympathetic nerve activity (MSNA). The aim of this study was to compare vascular sympathetic baroreflex sensitivity (BRS) in the same participants between the morning and afternoon. In 10 participants (mean age 22 ± 2.9 years), continuous measurements of blood pressure, heart rate and MSNA were made during 10 min of rest in the morning (between 0900 and 1000 h) and afternoon (between 1400 and 1500 h). Spontaneous vascular sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (vascular sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (vascular sympathetic BRStotal). Significant vascular sympathetic BRSinc and vascular sympathetic BRStotal slopes were obtained for 10 participants at both times of day. There was no significant difference in vascular sympathetic BRSinc between morning (−2.2 ± 0.6% bursts/mmHg) and afternoon (−2.5 ± 0.2% bursts/mmHg; P = 0.68) sessions. Similarly, vascular sympathetic BRStotal did not differ significantly between the morning (−3.0±0.5 AU/beat/mmHg) and afternoon (−2.9 ± 0.4 AU/beat/mmHg; P = 0.89). It is concluded that in healthy, young individuals baroreflex modulation of MSNA at rest does not differ between the morning and afternoon. The results indicate that recording MSNA at different times of the day is a valid means of assessing sympathetic function. PMID:26388723

  7. Baroreflex modulation of muscle sympathetic nerve activity at rest does not differ between morning and afternoon.

    PubMed

    Hissen, Sarah L; Macefield, Vaughan G; Brown, Rachael; Witter, Trevor; Taylor, Chloe E

    2015-01-01

    The incidence of cardiovascular events is significantly higher in the morning than other times of day. This has previously been associated with poor blood pressure control via the cardiac baroreflex. However, it is not known whether diurnal variation exists in vascular sympathetic baroreflex function, in which blood pressure is regulated via muscle sympathetic nerve activity (MSNA). The aim of this study was to compare vascular sympathetic baroreflex sensitivity (BRS) in the same participants between the morning and afternoon. In 10 participants (mean age 22 ± 2.9 years), continuous measurements of blood pressure, heart rate and MSNA were made during 10 min of rest in the morning (between 0900 and 1000 h) and afternoon (between 1400 and 1500 h). Spontaneous vascular sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (vascular sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (vascular sympathetic BRStotal). Significant vascular sympathetic BRSinc and vascular sympathetic BRStotal slopes were obtained for 10 participants at both times of day. There was no significant difference in vascular sympathetic BRSinc between morning (-2.2 ± 0.6% bursts/mmHg) and afternoon (-2.5 ± 0.2% bursts/mmHg; P = 0.68) sessions. Similarly, vascular sympathetic BRStotal did not differ significantly between the morning (-3.0±0.5 AU/beat/mmHg) and afternoon (-2.9 ± 0.4 AU/beat/mmHg; P = 0.89). It is concluded that in healthy, young individuals baroreflex modulation of MSNA at rest does not differ between the morning and afternoon. The results indicate that recording MSNA at different times of the day is a valid means of assessing sympathetic function. PMID:26388723

  8. [Changes in the activity of sympathetic-adrenal medullary system and hypothalamic-pituitary-adrenal system in humans exposed to psychogenic stressors and their effects on immunoreactivity].

    PubMed

    Simić, Natasa

    2010-10-01

    This paper gives an account of the functioning of the two systems in different stress induced situations. The activation of the sympathetic-adrenal medullary system is accompanied by the release of catecholamines, while the increased activity of the hypothalamic-pituitary-adrenal system results in the increased release of corticosteroids, especially cortisol. The role of the sympathetic-adrenal medullary system was investigated in immunologic changes induced by laboratory stressors. In the real, as in laboratory conditions, the effects of different stressors on the level of cortisol were studied, as it is the final product of the hypothalamic-pituitary-adrenal system activity. Additional (negative) effects on the functioning of these systems could induce some variables, as an increased consumption of alcohol, smoking, and sleeping disorder. Furthermore, the methodological shortcomings and the selection of subjects in previous studies are discussed. Previous results are also discussed, such as the immunosuppressive effects of cortisol, as well as the mediator and moderator variables in relation to stress and immunoreactivity.

  9. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries

    PubMed Central

    Nausch, Lydia W. M.; Bonev, Adrian D.; Heppner, Thomas J.; Tallini, Yvonne; Kotlikoff, Michael I.

    2012-01-01

    It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction. PMID:22140050

  10. Spike rate of multi-unit muscle sympathetic nerve fibers following catheter-based renal nerve ablation

    PubMed Central

    Tank, Jens; Heusser, Karsten; Brinkmann, Julia; Schmidt, Bernhard M.; Menne, Jan; Bauersachs, Johann; Haller, Hermann; Diedrich, André; Jordan, Jens

    2016-01-01

    Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates following renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition following renal denervation. We studied patients with difficult to control arterial hypertension (age 45–74 years) before, 6 (n=11), and 12 months (n=8) following renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA raw MSNA signal were analyzed. We detected MSNA action potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: −2±3 bpm; ΔSBP: 2±9 mmHg) or at 12 months (ΔHR: −1±3 mmHg, ΔSBP: −1±9 mmHg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34±3 bursts per minute and 8±1 spikes per sec. Both measurements did not change at 6 months (−1.4±3.6 bursts/minute; −0.6±1.4 spikes per sec) or at 12 months (−2.5±4.0 bursts/minute; −2.0±1.6 spikes per sec) following renal nerve ablation. After renal nerve ablation, BP decreased in 3 out of 11 patients. BP and MSNA spike frequency changes were not correlated (slope=−0.06; p=0.369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding following renal nerve ablation. PMID:26324745

  11. Spike rate of multi-unit muscle sympathetic nerve fibers after catheter-based renal nerve ablation.

    PubMed

    Tank, Jens; Heusser, Karsten; Brinkmann, Julia; Schmidt, Bernhard M; Menne, Jan; Bauersachs, Johann; Haller, Hermann; Diedrich, André; Jordan, Jens

    2015-10-01

    Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates after renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition after renal denervation. We studied patients with difficult-to-control arterial hypertension (age 45-74 years) before, 6 (n = 11), and 12 months (n = 8) after renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA and raw MSNA signals were analyzed. We detected MSNA action-potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: -2 ± 3 bpm; ΔSBP: 2 ± 9 mm Hg) or at 12 months (ΔHR: -1 ± 3 mm Hg, ΔSBP: -1 ± 9 mm Hg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34 ± 3 bursts per minute and 8 ± 1 spikes per second. Both measurements did not change at 6 months (-1.4 ± 3.6 bursts/minute; -0.6 ± 1.4 spikes/second) or at 12 months (-2.5 ± 4.0 bursts/minute; -2.0 ± 1.6 spikes/second) after renal nerve ablation. After renal nerve ablation, BP decreased in 3 of 11 patients. BP and MSNA spike frequency changes were not correlated (slope = -0.06; P = .369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding after renal nerve ablation. PMID:26324745

  12. Aged adrenal medullary tissue survives intraocular grafting, forms nerve fibers and responds to nerve growth factor.

    PubMed

    Strömberg, I; Ebendal, T

    1989-06-01

    Adrenal medullary tissue from aged (24 months old) and young adult (2 months old) rats was grafted to the anterior chamber of the eye of previously sympathectomized animals. Nerve growth factor (NGF) was administered by weekly bilateral intraocular injections. Five weeks postgrafting, irides were prepared as whole mounts and processed for Falck-Hillarp histochemistry for visualization of catecholamines. NGF appeared to partially prevent the reduction in volume that both old and young grafts underwent. In the presence of NGF, an extensive, dense fiber network, closely resembling the normal adrenergic innervation, was formed in the host irides by grafts from aged donors. The area of outgrowth from aged transplants without NGF treatment was as large as with NGF treatment but less dense. The reinnervation of irides by NGF-treated young adult grafts occupied a similar area as that seen with aged grafts, but the pattern of innervation was irregular, particularly close to the transplants. Transplants from young adult donors without NGF treatment generated a sparse, limited network of nerves in the irides. All grafts were tyrosine hydroxylase-, adrenaline-, and dopamine-beta-hydroxylase-immunoreactive in about the same proportion of cells, but the grafts from the young donors were smaller in size. We concluded that the ability of chromaffin cells to transform toward a neuronal phenotype, produce nerve fibers, and respond to exogenous NGF is maintained in aged adrenals. PMID:2754763

  13. Wavelet methods for spike detection in mouse renal sympathetic nerve activity.

    PubMed

    Brychta, Robert J; Tuntrakool, Sunti; Appalsamy, Martin; Keller, Nancy R; Robertson, David; Shiavi, Richard G; Diedrich, André

    2007-01-01

    Abnormal autonomic nerve traffic has been associated with a number of peripheral neuropathies and cardiovascular disorders prompting the development of genetically altered mice to study the genetic and molecular components of these diseases. Autonomic function in mice can be assessed by directly recording sympathetic nerve activity. However, murine sympathetic spikes are typically detected using a manually adjusted voltage threshold and no unsupervised detection methods have been developed for the mouse. Therefore, we tested the performance of several unsupervised spike detection algorithms on simulated murine renal sympathetic nerve recordings, including an automated amplitude discriminator and wavelet-based detection methods which used both the discrete wavelet transform (DWT) and the stationary wavelet transform (SWT) and several wavelet threshold rules. The parameters of the wavelet methods were optimized by comparing basal sympathetic activity to postmortem recordings and recordings made during pharmacological suppression and enhancement of sympathetic activity. In general, SWT methods were found to outperform amplitude discriminators and DWT methods with similar wavelet coefficient thresholding algorithms when presented with simulations with varied mean spike rates and signal-to-noise ratios. A SWT method which estimates the noise level using a "noise-only" wavelet scale and then selectively thresholds scales containing the physiologically important signal information was found to have the most robust spike detection. The proposed noise-level estimation method was also successfully validated during pharmacological interventions.

  14. Wavelet Methods for Spike Detection in Mouse Renal Sympathetic Nerve Activity

    PubMed Central

    Brychta, Robert J.; Tuntrakool, Sunti; Appalsamy, Martin; Keller, Nancy R.; Robertson, David; Shiavi, Richard G.; Diedrich, André

    2007-01-01

    Abnormal autonomic nerve traffic has been associated with a number of peripheral neuropathies and cardiovascular disorders prompting the development of genetically altered mice to study the genetic and molecular components of these diseases. Autonomic function in mice can be assessed by directly recording sympathetic nerve activity. However, murine sympathetic spikes are typically detected using a manually adjusted voltage threshold and no unsupervised detection methods have been developed for the mouse. Therefore, we tested the performance of several unsupervised spike detection algorithms on simulated murine renal sympathetic nerve recordings, including an automated amplitude discriminator and wavelet-based detection methods which used both the discrete wavelet transform (DWT) and the stationary wavelet transform (SWT) and several wavelet threshold rules. The parameters of the wavelet methods were optimized by comparing basal sympathetic activity to postmortem recordings and recordings made during pharmacological suppression and enhancement of sympathetic activity. In general, SWT methods were found to outperform amplitude discriminators and DWT methods with similar wavelet coefficient thresholding algorithms when presented with simulations with varied mean spike rates and signal-to-noise ratios. A SWT method which estimates the noise level using a “noise-only” wavelet scale and then selectively thresholds scales containing the physiologically important signal information was found to have the most robust spike detection. The proposed noise-level estimation method was also successfully validated during pharmacological interventions. PMID:17260859

  15. Adenosine triphosphate attenuates renal sympathetic nerve activity through left ventricular chemosensitive receptors.

    PubMed

    Taneyama, C; Benson, K T; Hild, P G; Goto, H

    1997-02-01

    We previously reported that ATP, but not adenosine, administered i.v. attenuates the baroreflex-mediated increase in sympathetic nerve activity in response to arterial hypotension by a vagal afferent mechanism. It was not elucidated in that study which vagal afferent endings are involved. Mongrel dogs were anesthetized with alpha-chloralose, thoracotomy was performed and a 27-gauge hypodermic needle was inserted into the left circumflex coronary artery. The left renal sympathetic nerves were isolated and placed on a bipolar silver electrode for measurement of renal sympathetic nerve activity (RSNA). Dose-response effects of intracoronary or i.v. infusion of ATP (100, 200 or 400 microg/kg/min) on RSNA and mean arterial pressure were studied in neuraxis-intact and cervically vagotomized dogs. RSNA was increased dose-dependently with decreasing mean arterial pressure during the i.v. ATP infusion. Elevation of RSNA was attenuated by higher intracoronary ATP infusion rates, despite the fact that mean arterial pressure was decreased dose-dependently. Left ventricular end-diastolic pressure, however, remained unchanged. This suppression of RSNA by the intracoronary ATP infusion was completely abolished by bilateral cervical vagotomy. Our data suggest that ATP attenuates reflex increases in sympathetic nerve activity by possibly stimulating ventricular chemoreceptors with cardiac vagal afferents. PMID:9023265

  16. Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure

    PubMed Central

    Barnes, Maria J.; McDougal, David H.

    2014-01-01

    Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb). Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3 μg; 40 nL) into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP) and renal sympathetic nerve activity (RSNA). When the 3 μg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1 ng), it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin's actions within the RVLM may influence blood pressure and renal sympathetic nerve activity. PMID:25152707

  17. Afferent vagal nerve stimulation resets baroreflex neural arc and inhibits sympathetic nerve activity

    PubMed Central

    Saku, Keita; Kishi, Takuya; Sakamoto, Kazuo; Hosokawa, Kazuya; Sakamoto, Takafumi; Murayama, Yoshinori; Kakino, Takamori; Ikeda, Masataka; Ide, Tomomi; Sunagawa, Kenji

    2014-01-01

    Abstract It has been established that vagal nerve stimulation (VNS) benefits patients and/or animals with heart failure. However, the impact of VNS on sympathetic nerve activity (SNA) remains unknown. In this study, we investigated how vagal afferent stimulation (AVNS) impacts baroreflex control of SNA. In 12 anesthetized Sprague–Dawley rats, we controlled the pressure in isolated bilateral carotid sinuses (CSP), and measured splanchnic SNA and arterial pressure (AP). Under a constant CSP, increasing the voltage of AVNS dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA was ‐28.0 ± 10.3%. To evaluate the dynamic impacts of AVNS on SNA, we performed random AVNS using binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer functions of the native baroreflex from CSP to SNA (neural arc) and from SNA to AP (peripheral arc). The transfer function from AVNS to SNA strikingly resembled the baroreflex neural arc and the transfer functions of SNA to AP were indistinguishable whether we perturbed ANVS or CSP, indicating that they likely share common central and peripheral neural mechanisms. To examine the impact of AVNS on baroreflex, we changed CSP stepwise and measured SNA and AP responses with or without AVNS. AVNS resets the sigmoidal neural arc downward, but did not affect the linear peripheral arc. In conclusion, AVNS resets the baroreflex neural arc and induces sympathoinhibition in the same manner as the control of SNA and AP by the native baroreflex. PMID:25194023

  18. Modelling the vascular response to sympathetic postganglionic nerve activity

    PubMed Central

    Briant, Linford J.B.; Paton, Julian F.R.; Pickering, Anthony E.; Champneys, Alan R.

    2015-01-01

    This paper explores the influence of burst properties of the sympathetic nervous system on arterial contractility. Specifically, a mathematical model is constructed of the pathway from action potential generation in a sympathetic postganglionic neurone to contraction of an arterial smooth muscle cell. The differential equation model is a synthesis of models of the individual physiological processes, and is shown to be consistent with physiological data. The model is found to be unresponsive to tonic (regular) stimulation at typical frequencies recorded in sympathetic efferents. However, when stimulated at the same average frequency, but with repetitive respiratory-modulated burst patterns, it produces marked contractions. Moreover, the contractile force produced is found to be highly dependent on the number of spikes in each burst. In particular, when the model is driven by preganglionic spike trains recorded from wild-type and spontaneously hypertensive rats (which have increased spiking during each burst) the contractile force was found to be 10-fold greater in the hypertensive case. An explanation is provided in terms of the summative increased release of noradrenaline. Furthermore, the results suggest the marked effect that hypertensive spike trains had on smooth muscle cell tone can provide a significant contribution to the pathology of hypertension. PMID:25698230

  19. Lineage and stage specific requirement for Dicer1 in sympathetic ganglia and adrenal medulla formation and maintenance.

    PubMed

    Stubbusch, Jutta; Narasimhan, Priyanka; Hennchen, Melanie; Huber, Katrin; Unsicker, Klaus; Ernsberger, Uwe; Rohrer, Hermann

    2015-04-15

    The development of sympathetic neurons and chromaffin cells is differentially controlled at distinct stages by various extrinsic and intrinsic signals. Here we use conditional deletion of Dicer1 in neural crest cells and noradrenergic neuroblasts to identify stage specific functions in sympathoadrenal lineages. Conditional Dicer1 knockout in neural crest cells of Dicer1(Wnt1Cre) mice results in a rapid reduction in the size of developing sympathetic ganglia and adrenal medulla. In contrast, Dicer1 elimination in noradrenergic neuroblasts of Dicer1(DbhiCre) animals affects sympathetic neuron survival starting at late embryonic stages and chromaffin cells persist at least until postnatal week 1. A differential function of Dicer1 signaling for the development of embryonic noradrenergic and cholinergic sympathetic neurons is demonstrated by the selective increase in the expression of Tlx3 and the cholinergic marker genes VAChT and ChAT at E16.5. The number of Dbh, Th and TrkA expressing noradrenergic neurons is strongly decreased in Dicer1-deficient sympathetic ganglia at birth, whereas Tlx3(+)/ Ret(+) cholinergic neurons cells are spared from cell death. The postnatal death of chromaffin cells is preceded by the loss of Ascl1, mir-375 and Pnmt and an increase in the markers Ret and NF-M, which suggests that Dicer1 is required for the maintenance of chromaffin cell differentiation and survival. Taken together, these findings demonstrate distinct stage and lineage specific functions of Dicer1 signaling in differentiation and survival of sympathetic neurons and adrenal chromaffin cells. PMID:25661788

  20. Neuroplasticity of Sensory and Sympathetic Nerve Fibers in the Painful Arthritic Joint

    PubMed Central

    Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Coughlin, Kathleen; Kaczmarska, Magdalena J.; Castaneda-Corral, Gabriela; Bloom, Aaron P.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2012-01-01

    Objective Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization. Methods A painful arthritic knee joint was produced by injection of complete Freund’s adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages). Results In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, CGRP+, NF200+, GAP43+, and TH+ nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages. Conclusions Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain. PMID:22246649

  1. Effect of percutaneous renal sympathetic nerve radiofrequency ablation in patients with severe heart failure.

    PubMed

    Dai, Qiming; Lu, Jing; Wang, Benwen; Ma, Genshan

    2015-01-01

    This study aimed to investigate the clinical feasibility and effects of percutaneous renal sympathetic nerve radiofrequency ablation in patients with heart failure. A total of 20 patients with heart failure were enrolled, aged from 47 to 75 years (63±10 years). They were divided into the standard therapy (n = 10), and renal nerve radiofrequency ablation groups (n = 10). There were 15 males and 5 female patients, including 8 ischemic cardiomyopathy, 8 dilated cardiomyopathy, and 8 hypertensive cardiopathy. All of the patients met the criteria of New York Heart Association classes III-IV cardiac function. Patients with diabetes and renal failure were excluded. Percutaneous renal sympathetic nerve radiofrequency ablation was performed on the renal artery wall under X-ray guidance. Serum electrolytes, neurohormones, and 24 h urine volume were recorded 24 h before and after the operation. Echocardiograms were performed to obtain left ventricular ejection fraction at baseline and 6 months. Heart rate, blood pressure, symptoms of dyspnea and edema were also monitored. After renal nerve ablation, 24 h urine volume was increased, while neurohormone levels were decreased compared with those of pre-operation and standard therapy. No obvious change in heart rate or blood pressure was recorded. Symptoms of heart failure were improved in patients after the operation. No complications were recorded in the study. Percutaneous renal sympathetic nerve radiofrequency ablation may be a feasible, safe, and effective treatment for the patients with severe congestive heart failure.

  2. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction.

    PubMed

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  3. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction

    PubMed Central

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  4. Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors

    PubMed Central

    Richeri, Analía; Bianchimano, Paola; Mármol, Nelson M; Viettro, Lorena; Cowen, Timothy; Brauer, M Mónica

    2005-01-01

    Uterine sympathetic innervation undergoes profound remodelling in response to physiological and experimental changes in the circulating levels of sex hormones. It is not known, however, whether this plasticity results from changes in the innervating neurons, the neuritogenic properties of the target tissue or both. Using densitometric immunohistochemistry, we analysed the effects of prepubertal chronic oestrogen treatment (three subcutaneous injections of 20 µg of β-oestradiol 17-cypionate on days 25, 27 and 29 after birth), natural peripubertal transition and late pregnancy (19–20 days post coitum) on the levels of TrkA and p75 nerve growth factor receptors in uterine-projecting sympathetic neurons of the thoraco-lumbar paravertebral sympathetic chain (T7–L2) identified using the retrograde tracer Fluorogold. For comparative purposes, levels of TrkA and p75 were assessed in the superior cervical ganglion (SCG) following prepubertal chronic oestrogen treatment. These studies showed that the vast majority of uterine-projecting neurons expressed both TrkA and p75. Both prepubertal chronic oestrogen treatment and the peripubertal transition increased the ratio p75 to TrkA in uterine-projecting neurons, whereas pregnancy elicited the opposite effect. Prepubertal chronic oestrogen treatment had no effects on levels of TrkA or p75 in sympathetic neurons of the SCG. Taken together, our data suggest that neurotrophin receptor-mediated events may contribute to regulate sex hormone-induced plasticity in uterine sympathetic nerves, and are in line with the idea that, in vivo, plasticity in uterine nerves involves changes in both the target and the innervating neurons. PMID:16050899

  5. Spike detection in human muscle sympathetic nerve activity using the kurtosis of stationary wavelet transform coefficients

    PubMed Central

    Brychta, Robert J.; Shiavi, Richard; Robertson, David; Diedrich, André

    2007-01-01

    The accurate assessment of autonomic sympathetic function is important in the diagnosis and study of various autonomic and cardiovascular disorders. Sympathetic function in humans can be assessed by recording the muscle sympathetic nerve activity, which is characterized by synchronous neuronal discharges separated by periods of neural silence dominated by colored Gaussian noise. The raw nerve activity is generally rectified, integrated, and quantified using the integrated burst rate or area. We propose an alternative quantification involving spike detection using a two-stage stationary wavelet transform (SWT) de-noising method. The SWT coefficients are first separated into noise-related and burst-related coefficients on the basis of their local kurtosis. The noise-related coefficients are then used to establish a threshold to identify spikes within the bursts. This method demonstrated better detection performance than an unsupervised amplitude discriminator and similar wavelet-based methods when confronted with simulated data of varying burst rate and signal to noise ratio. Additional validation on data acquired during a graded head-up tilt protocol revealed a strong correlation between the mean spike rate and the mean integrate burst rate (r = 0.85) and burst area rate (r = 0.91). In conclusion, the kurtosis-based wavelet de-noising technique is a potentially useful method of studying sympathetic nerve activity in humans. PMID:17083982

  6. Spike detection in human muscle sympathetic nerve activity using the kurtosis of stationary wavelet transform coefficients.

    PubMed

    Brychta, Robert J; Shiavi, Richard; Robertson, David; Diedrich, André

    2007-03-15

    The accurate assessment of autonomic sympathetic function is important in the diagnosis and study of various autonomic and cardiovascular disorders. Sympathetic function in humans can be assessed by recording the muscle sympathetic nerve activity, which is characterized by synchronous neuronal discharges separated by periods of neural silence dominated by colored Gaussian noise. The raw nerve activity is generally rectified, integrated, and quantified using the integrated burst rate or area. We propose an alternative quantification involving spike detection using a two-stage stationary wavelet transform (SWT) de-noising method. The SWT coefficients are first separated into noise-related and burst-related coefficients on the basis of their local kurtosis. The noise-related coefficients are then used to establish a threshold to identify spikes within the bursts. This method demonstrated better detection performance than an unsupervised amplitude discriminator and similar wavelet-based methods when confronted with simulated data of varying burst rate and signal to noise ratio. Additional validation on data acquired during a graded head-up tilt protocol revealed a strong correlation between the mean spike rate and the mean integrate burst rate (r=0.85) and burst area rate (r=0.91). In conclusion, the kurtosis-based wavelet de-noising technique is a potentially useful method of studying sympathetic nerve activity in humans.

  7. Relation between QT interval variability and muscle sympathetic nerve activity in normal subjects.

    PubMed

    El-Hamad, Fatima; Lambert, Elisabeth; Abbott, Derek; Baumert, Mathias

    2015-10-01

    Beat-to-beat variability of the QT interval (QTV) is sought to provide an indirect noninvasive measure of sympathetic nerve activity, but a formal quantification of this relationship has not been provided. In this study we used power contribution analysis to study the relationship between QTV and muscle sympathetic nerve activity (MSNA). ECG and MSNA were recorded in 10 healthy subjects in the supine position and after 40° head-up tilt. Power spectrum analysis was performed using a linear autoregressive model with two external inputs: heart period (RR interval) variability (RRV) and MSNA. Total and low-frequency power of QTV was decomposed into contributions by RRV, MSNA, and sources independent of RRV and MSNA. Results show that the percentage of MSNA power contribution to QT is very small and does not change with tilt. RRV power contribution to QT power is notable and decreases with tilt, while the greatest percentage of QTV is independent of RRV and MSNA in the supine position and after 40° head-up tilt. In conclusion, beat-to-beat QTV in normal subjects does not appear to be significantly affected by the rhythmic modulations in MSNA following low to moderate orthostatic stimulation. Therefore, MSNA oscillations may not represent a useful surrogate for cardiac sympathetic nerve activity at moderate levels of activation, or, alternatively, sympathetic influences on QTV are complex and not quantifiable with linear shift-invariant autoregressive models. PMID:26276814

  8. A clinician's perspective of the role of renal sympathetic nerves in hypertension

    PubMed Central

    Briasoulis, Alexandros; Bakris, George L.

    2015-01-01

    The renal sympathetic nerves have significant contribution to the control of different aspects of kidney function. Early animal studies of renal denervation in a large number of different models of hypertension showed that that RDN improved BP control. Recently, data from prospective cohorts and randomized studies showed that renal denervation therapy (RDN) is a safe procedure but is associated with only modest reduction of ambulatory blood pressure (BP) in patients on intensive medical therapy. The main goal of this article is to review the results of preclinical and clinical studies on the contribution of the renal sympathetic nervous system to hypertension and the therapeutic applications of catheter-based renal denervation. PMID:25859218

  9. Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans.

    PubMed

    White, Daniel W; Shoemaker, J Kevin; Raven, Peter B

    2015-12-01

    The technique of microneurography and the assessment of muscle sympathetic nerve activity (MSNA) are used in laboratories throughout the world. The variables used to describe MSNA, and the criteria by which these variables are quantified from the integrated neurogram, vary among studies and laboratories and, therefore, can become confusing to those starting to learn the technique. Therefore, the purpose of this educational review is to discuss guidelines and standards for the assessment of sympathetic nervous activity through the collection and analysis of MSNA. This review will reiterate common practices in the collection of MSNA, but will also introduce considerations for the evaluation and physiological inference using MSNA.

  10. Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans.

    PubMed

    White, Daniel W; Shoemaker, J Kevin; Raven, Peter B

    2015-12-01

    The technique of microneurography and the assessment of muscle sympathetic nerve activity (MSNA) are used in laboratories throughout the world. The variables used to describe MSNA, and the criteria by which these variables are quantified from the integrated neurogram, vary among studies and laboratories and, therefore, can become confusing to those starting to learn the technique. Therefore, the purpose of this educational review is to discuss guidelines and standards for the assessment of sympathetic nervous activity through the collection and analysis of MSNA. This review will reiterate common practices in the collection of MSNA, but will also introduce considerations for the evaluation and physiological inference using MSNA. PMID:26299824

  11. Decreased receptivity of pathway connective tissue to sympathetic nerve ingrowth in the developing rat.

    PubMed

    Hiebert, J M; Fan, Q; Smith, P G

    1997-05-20

    Sympathetic axons can form atypical pathways to denervated orbital targets in neonatal rats but not in rats aged 30 or more days. The objective of this study was to determine if connective tissue pathways that carry sympathetic nerves lose their ability to sustain axonal sprouting during the early postnatal period. Regions of periorbital sheath known to contain large numbers of sympathetic axons that travel to distal orbital targets were excised from rats (sympathectomized 3 days previously) on postnatal days 6-7, 14-15, 30-31, and 48-49 and placed in anterior chambers of adult host rats. Tissues were removed 3, 6, or 10 days post-transplant and sympathetic ingrowth was analyzed by catecholamine histofluorescence in whole-mount or cryosectioned specimens. Connective tissue transplants from 6-15-day-old donors showed significant fiber ingrowth by 3 days in oculo, and innervation was maximal by 6 days. In contrast, sprouting into 30-49-day-old tissue was significantly slower, with most transplants lacking fibers at 3 days, and with small numbers of short fibers present at 6 days. We conclude that maturational changes occur in periorbital connective tissue pathways in the early postnatal period which make them less receptive to ingrowth by sympathetic nerves. The findings that connective tissue pathways are better substrates for sympathetic sprouting in the neonatal rat supports the view that developmental changes in these tissues are likely to contribute to the impaired reinnervation of orbital targets by contralateral neurons in juvenile and adult rats. PMID:9174244

  12. Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats

    NASA Technical Reports Server (NTRS)

    Moffitt, J. A.; Foley, C. M.; Schadt, J. C.; Laughlin, M. H.; Hasser, E. M.

    1998-01-01

    The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/- 11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6 vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs. 453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13 +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

  13. The chelonian spinal nerve ganglia are a conglomerate of the spinal nerve ganglia proper and the sympathetic ganglia.

    PubMed

    Kadota, Tetsuo; Nakano, Masato; Atobe, Yoshitoshi; Goris, Richard C; Funakoshi, Kengo

    2009-01-01

    A tyrosine hydroxylase-immunoreactive cell mass is found in the caudal portion of the dorsal nerve ganglion of the red-eared slider, Trachemys scripta elegans. The ganglion appears as a flat oval structure in the horizontal plane, where the major axis runs latero-medially, and the minor axis rostro-caudally in the ventral view. A communicating branch to the sympathetic chain diverges from the top of each tubercle which lies on the caudo-lateral side of the ganglion. A tyrosine hydroxylase- immunoreactive cell mass is located in this tubercle. This cell mass exists in both sexes. Tyrosine hydroxylase-immunoreactive cells, that contain Nissl bodies in cytoplasm and are enveloped by the satellite cells, are multipolar and their neural processes are distributed in a distal direction into the spinal nerve. The range of distribution of the synapsin I-immunoreactive structures is limited to the tyrosine hydroxylase-immunoreactive cell mass. The chelonian dorsal spinal nerve ganglia are a conglomerate of the spinal nerve ganglion proper and the sympathetic ganglion.

  14. Thoracic origin of a sympathetic supply to the upper limb: the ‘nerve of Kuntz’ revisited

    PubMed Central

    RAMSAROOP, L.; PARTAB, P.; SINGH, B.; SATYAPAL, K. S.

    2001-01-01

    An understanding of the origin of the sympathetic innervation of the upper limb is important in surgical sympathectomy procedures. An inconstant intrathoracic ramus which joined the 2nd intercostal nerve to the ventral ramus of the 1st thoracic nerve, proximal to the point where the latter gave a large branch to the brachial plexus, has become known as the ‘nerve of Kuntz’ (Kuntz, 1927). Subsequently a variety of sympathetic interneuronal connections down to the 5th intercostal space were reported and also described as the nerve of Kuntz. The aim of this study was to determine: (1) the incidence, location and course of the nerve of Kuntz; (2) the relationship of the nerve of Kuntz to the 2nd thoracic ganglion; (3) the variations of the nerve of Kuntz in the absence of a stellate ganglion; (4) to compare the original intrathoracic ramus with sympathetic variations at other intercostal levels; and (5) to devise an appropriate anatomical classification of the nerves of Kuntz. Bilateral microdissection of the sympathetic chain and somatic nerves of the upper 5 intercostal spaces was undertaken in 32 fetuses (gestational age, 18 wk to full term) and 18 adult cadavers. The total sample size comprised 99 sides. Sympathetic contributions to the first thoracic nerve were found in 60 of 99 sides (left 32, right 28). Of these, 46 were confined to the 1st intercostal space only. The nerve of Kuntz (the original intrathoracic ramus) of the 1st intercostal space had a demonstrable sympathetic connection in 34 cases, and an absence of macroscopic sympathetic connections in 12. In the remaining intercostal spaces, intrathoracic rami uniting intercostal nerves were not observed. Additional sympathetic contributions (exclusive of rami communicantes) were noted between ganglia, interganglionic segments and intercostal nerves as additional rami communicantes. The eponym nerve of Kuntz should be restricted to descriptions of the intrathoracic ramus of the 1st intercostal space. Any

  15. Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space

    NASA Technical Reports Server (NTRS)

    Ertl, Andrew C.; Diedrich, Andre; Biaggioni, Italo; Levine, Benjamin D.; Robertson, Rose Marie; Cox, James F.; Zuckerman, Julie H.; Pawelczyk, James A.; Ray, Chester A.; Buckey, Jay C Jr; Lane, Lynda D.; Shiavi, Richard; Gaffney, F. Andrew; Costa, Fernando; Holt, Carol; Blomqvist, C. Gunnar; Eckberg, Dwain L.; Baisch, Friedhelm J.; Robertson, David

    2002-01-01

    Astronauts returning from space have reduced red blood cell masses, hypovolaemia and orthostatic intolerance, marked by greater cardio-acceleration during standing than before spaceflight, and in some, orthostatic hypotension and presyncope. Adaptation of the sympathetic nervous system occurring during spaceflight may be responsible for these postflight alterations. We tested the hypotheses that exposure to microgravity reduces sympathetic neural outflow and impairs sympathetic neural responses to orthostatic stress. We measured heart rate, photoplethysmographic finger arterial pressure, peroneal nerve muscle sympathetic activity and plasma noradrenaline spillover and clearance, in male astronauts before, during (flight day 12 or 13) and after the 16 day Neurolab space shuttle mission. Measurements were made during supine rest and orthostatic stress, as simulated on Earth and in space by 7 min periods of 15 and 30 mmHg lower body suction. Mean (+/- S.E.M.) heart rates before lower body suction were similar pre-flight and in flight. Heart rate responses to -30 mmHg were greater in flight (from 56 +/- 4 to 72 +/- 4 beats min(-1)) than pre-flight (from 56 +/- 4 at rest to 62 +/- 4 beats min(-1), P < 0.05). Noradrenaline spillover and clearance were increased from pre-flight levels during baseline periods and during lower body suction, both in flight (n = 3) and on post-flight days 1 or 2 (n = 5, P < 0.05). In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33 %) in the same three subjects in whom noradrenaline spillover and clearance were increased. The sympathetic response to 30 mmHg lower body suction was at pre-flight levels or higher in each subject (35 pre-flight vs. 40 bursts min(-1) in flight). No astronaut experienced presyncope during lower body suction in space (or during upright tilt following the Neurolab mission). We conclude that in space, baseline sympathetic neural outflow is increased moderately and sympathetic

  16. Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus.

    PubMed

    Carter, Stephen J; Hodges, Gary J

    2011-11-01

    We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42 °C or rapidly to 44 °C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42 °C; (2) EMLA 42 °C; (3) control 44°C; and (4) EMLA 44 °C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42 °C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44 °C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42 °C; (2) BT 42 °C; (3) control 44 °C; and (4) BT 44 °C. Treatment with BT at the 42 °C sites resulted in a marked reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44 °C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus.

  17. A study of the sympathetic skin response and sensory nerve action potential after median and ulnar nerve repair.

    PubMed

    Jazayeri, M; Ghavanini, M R; Rahimi, H R; Raissi, G R

    2003-01-01

    The purpose of this study was to compare SSR with sensory nerve action potential (SNAP) responses in regeneration of injured peripheral nerves after nerve repair. We studied 10 male patients with a mean age of 26.7 years. All the patients had complete laceration of median or ulnar nerves. The patients were followed up at least for six months. SSR and SNAP assessment were performed every one to two months. Normal hands were used as controls. SSR was positive after 15.8 +/- 9.4 weeks (mean +/- 2 SD) and SNAP after 27.8 +/- 12.9 weeks (mean +/- 2 SD). The difference was statistically significant (P value < 0.001). This can be due to more rapid growth of sympathetic unmyelinated fibers relative to sensory myelinated fibers. This study also shows that recovery of the sudomotor activity following nerve repair is satisfactory in general and SSR can be used as a useful and sensitive method in the evaluation of sudomotor nerve regeneration.

  18. Differential distribution of muscle and skin sympathetic nerve activity in patients with end-stage renal disease

    PubMed Central

    Park, Jeanie; Campese, Vito M.; Nobakht, Niloofar; Middlekauff, Holly R.

    2008-01-01

    End-stage renal disease (ESRD) is characterized by resting sympathetic overactivity. Baseline muscle sympathetic nerve activity (MSNA), which is governed by baroreflexes and chemoreflexes, is elevated in ESRD. Whether resting skin sympathetic nerve activity (SSNA), which is independent from baroreflex and chemoreflex control, is also elevated has never been reported in renal failure. The purpose of this study was to determine whether sympathetic overactivity of ESRD is generalized to include the skin distribution. We measured sympathetic nerve activity to both muscle and skin using microneurography in eight ESRD patients and eight controls. MSNA was significantly (P = 0.025) greater in ESRD (37.3 ± 3.6 bursts/min) when compared with controls (23.1 ± 4.4 bursts/min). However, SSNA was not elevated in ESRD (ESRD vs. controls, 17.6 ± 2.2 vs. 16.1 ± 1.7 bustst/min, P = 0.61). Similar results were obtained when MSNA was quantified as bursts per 100 heartbeats. We report the novel finding that although sympathetic activity directed to muscle is significantly elevated, activity directed to skin is not elevated in ESRD. The differential distribution of sympathetic outflow to the muscle vs. skin in ESRD is similar to the pattern seen in other disease states characterized by sympathetic overactivity such as heart failure and obesity. PMID:18845779

  19. Differential distribution of muscle and skin sympathetic nerve activity in patients with end-stage renal disease.

    PubMed

    Park, Jeanie; Campese, Vito M; Nobakht, Niloofar; Middlekauff, Holly R

    2008-12-01

    End-stage renal disease (ESRD) is characterized by resting sympathetic overactivity. Baseline muscle sympathetic nerve activity (MSNA), which is governed by baroreflexes and chemoreflexes, is elevated in ESRD. Whether resting skin sympathetic nerve activity (SSNA), which is independent from baroreflex and chemoreflex control, is also elevated has never been reported in renal failure. The purpose of this study was to determine whether sympathetic overactivity of ESRD is generalized to include the skin distribution. We measured sympathetic nerve activity to both muscle and skin using microneurography in eight ESRD patients and eight controls. MSNA was significantly (P = 0.025) greater in ESRD (37.3 +/- 3.6 bursts/min) when compared with controls (23.1 +/- 4.4 bursts/min). However, SSNA was not elevated in ESRD (ESRD vs. controls, 17.6 +/- 2.2 vs. 16.1 +/- 1.7 bustst/min, P = 0.61). Similar results were obtained when MSNA was quantified as bursts per 100 heartbeats. We report the novel finding that although sympathetic activity directed to muscle is significantly elevated, activity directed to skin is not elevated in ESRD. The differential distribution of sympathetic outflow to the muscle vs. skin in ESRD is similar to the pattern seen in other disease states characterized by sympathetic overactivity such as heart failure and obesity.

  20. Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium

    PubMed Central

    Weidler, C; Holzer, C; Harbuz, M; Hofbauer, R; Angele, P; Scholmerich, J; Straub, R

    2005-01-01

    Objective: To investigate the correlation between density of nerve fibres and the presence of BDNF+ cells. Methods: Densities of nerve fibres and BDNF+ cells were detected by quantitative immunohistochemistry in fresh synovial tissue from 52 patients with RA, 59 with OA, and 26 controls (Co). BDNF was also detected by in situ hybridisation. Results: Sympathetic nerve fibre density was similar in Co and OA but markedly reduced in RA (p = 0.002), whereas density of substance P positive (SP+) sensory nerve fibres was lower in OA than in Co and RA (p = 0.002). The ratio of sympathetic/SP+ sensory nerve fibre density was highest in OA and Co, followed by RA. The correlation between density of sympathetic nerve fibres and SP+ sensory nerve fibres in OA (R = 0.425, p = 0.001) was strongly positive, had a positive trend in Co (R = 0.243, NS), but was negative in RA (R = –0.292, p = 0.040). In RA and OA tissue the density of BDNF+ cells was high in sublining areas but markedly lower in Co (p = 0.001). BDNF+ cell density correlated positively with the ratio of sympathetic/SP+ sensory nerve fibre density in Co (R = 0.433, p = 0.045) and in OA (R = 0.613, p = 0.015), but not in RA (R = 0.101, NS). Immunohistochemical double staining demonstrated that some macrophages and fibroblasts were positive for BDNF. Conclusions: The correlation of density of SP+ sensory with sympathetic nerve fibres was positive in Co and OA but negative in RA. BDNF may have a stimulatory role on growth of sympathetic in relation to SP+ sensory nerve fibres in Co and OA, but not in RA. PMID:15608299

  1. Infarction-induced cytokines cause local depletion of tyrosine hydroxylase in cardiac sympathetic nerves

    PubMed Central

    Parrish, Diana C.; Alston, Eric N.; Rohrer, Hermann; Nkadi, Paul; Woodward, William R.; Schütz, Günther; Habecker, Beth A.

    2010-01-01

    Myocardial infarction causes heterogeneity of noradrenergic transmission that contributes to the development of ventricular arrhythmias and sudden cardiac death. Ischemia-induced alterations in sympathetic transmission include regional variations in cardiac norepinephrine (NE) and in tyrosine hydroxylase, the rate-limiting enzyme in NE synthesis. Inflammatory cytokines that act through gp130 are elevated in the heart after myocardial infarction. These cytokines decrease expression of tyrosine hydroxylase in sympathetic neurons, and indirect evidence suggests they contribute to the local depletion of tyrosine hydroxylase in the damaged left ventricle. However, gp130 cytokines are also important for the survival of cardiac myocytes following damage to the heart. To examine the effect of cytokines on tyrosine hydroxylase and NE content in cardiac nerves we used gp130DBH-Cre/lox mice, which have a deletion of the gp130 receptor in neurons expressing dopamine beta hydroxylase. The absence of neuronal gp130 prevented the loss of tyrosine hydroxylase in cardiac sympathetic nerves innervating the left ventricle one week after ischemia-reperfusion. Surprisingly, restoring tyrosine hydroxylase in the damaged ventricle did not return neuronal NE content to normal levels. NE uptake into cardiac nerves was significantly lower in gp130 KO mice, contributing to the lack of neuronal NE stores. There were no significant differences in left ventricular peak systolic pressure, dP/dtMAX, or dP/dtMIN between the two genotypes after myocardial infarction, but ganglionic blockade revealed differences in autonomic tone between the genotypes. Stimulating the heart with dobutamine or releasing endogenous NE with tyramine generated similar responses in both genotypes. Thus, the removal of gp130 from sympathetic neurons prevents the post-infarct depletion of TH in the left ventricle, but does not alter NE content or cardiac function. PMID:19880537

  2. Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

    PubMed

    Thaung, H P Aye; Baldi, J Chris; Wang, Heng-Yu; Hughes, Gillian; Cook, Rosalind F; Bussey, Carol T; Sheard, Phil W; Bahn, Andrew; Jones, Peter P; Schwenke, Daryl O; Lamberts, Regis R

    2015-08-01

    Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart.

  3. Skin Sympathetic Nerve Activity is Modulated during Slow Sinusoidal Linear Displacements in Supine Humans

    PubMed Central

    Bolton, Philip S.; Hammam, Elie; Kwok, Kenny; Macefield, Vaughan G.

    2016-01-01

    Low-frequency sinusoidal linear acceleration (0.08 Hz, ±4 mG) modulates skin sympathetic nerve activity (SSNA) in seated subjects (head vertical), suggesting that activation of the utricle in the peripheral vestibular labyrinth modulates SSNA. The aim of the current study was to determine whether SSNA is also modulated by input from the saccule. Tungsten microelectrodes were inserted into the common peroneal nerve to record oligounitary SSNA in 8 subjects laying supine on a motorized platform with the head aligned with the longitudinal axis of the body. Slow sinusoidal (0.08 Hz, 100 cycles) linear acceleration-decelerations (peak ±4 mG) were applied rostrocaudally to predominately activate the saccules, or mediolaterally to predominately activate the utricles. Cross-correlation histograms were constructed between the negative-going sympathetic spikes and the positive peaks of the sinusoidal stimuli. Sinusoidal linear acceleration along the rostrocaudal axis or mediolateral axis both resulted in sinusoidal modulation of SSNA (Median, IQR 27.0, 22–33% and 24.8, 17–39%, respectively). This suggests that both otolith organs act on sympathetic outflow to skin and muscle in a similar manner during supine displacements. PMID:26909019

  4. On the secretory activity of single varicosities in the sympathetic nerves innervating the rat tail artery.

    PubMed

    Astrand, P; Stjärne, L

    1989-02-01

    1. Nerve terminal impulses (NTIs) and spontaneous or stimulus-evoked excitatory junction currents (SEJCs or EJCs), reflecting secretion of transmitter quanta from release sites in the sympathetic nerves of rat tail artery, were recorded by extracellular electrodes. 2. The release of transmitter quanta from single varicosities was analysed on a pulse-by-pulse basis. 3. Since the SEJCs were tetrodotoxin-resistant, and hence probably caused by single quanta, they were employed to analyse the quantal content of EJCs. 4. In the majority of recordings, EJCs were large compared to SEJCs from the same attachment, and preceded by prominent NTIs. This type of activity appeared to reflect simultaneous activation of several nerve fibres and numerous varicosities. 5. By focal stimulation, it was usually possible to improve the resolution by examining spots in which a large proportion of the suprathreshold stimuli failed to cause EJCs. Here, averaged NTIs preceding large EJCs were indistinguishable from averaged NTIs not followed by EJCs. Thus, failure of invasion by the nerve impulse was not a cause of the frequent secretory failure. 6. In these attachments the amplitude distribution of nerve stimulus-evoked EJCs was similar to that of the SEJCs and many individual EJCs could be matched in amplitude and time course by SEJCs. Thus, transmitter secretion from these sympathetic nerve varicosities seems to be basically monoquantal. 7. Under conditions when all EJCs were smaller than or equal to the largest SEJCs some characteristic EJC profiles appeared only a few times in response to several hundred suprathreshold stimuli at low frequency (0.5-1 Hz). Using tentatively these EJCs as 'fingerprints' of single quanta from particular release sites, the probability for activation of individual release sites ranges from 0.002 to 0.02.

  5. 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.

  6. [The state of sympathetic-adrenal system in patients with chronic cardiac insufficiency].

    PubMed

    Nigmatullin, R R; Kirillova, V V; Dzhordzhikiia, R K; Kudrin, V S; Klodt, P M

    2009-01-01

    Activation of sympato-adrenal system plays an important role in the development of chronic cardiac failure (CCF). However, its relation to morpho-functional state of myocardium in CCF patients is virtually unknown. HPLC with electrochemical detection was used to determine plasma noradrenalin, adrenalin, and their precursors, 3,4-dioxyphenylalanine (DOPA) and dopamine, in patients with different morpho-functional changes in myocardium. The study demonstrated enhanced activity of sympato-adrenal system in patients with CCF. It showed for the first time that activity of sympato-adrenal system in CCF patients depends on the morpho-functional status of myocardium.

  7. Topohistology of sympathetic and parasympathetic nerve fibers in branches of the pelvic plexus: an immunohistochemical study using donated elderly cadavers

    PubMed Central

    Hieda, Keisuke; Sasaki, Hiromasa; Murakami, Gen; Abe, Shinichi; Matsubara, Akio; Miyake, Hideaki; Fujisawa, Masato

    2014-01-01

    Although the pelvic autonomic plexus may be considered a mixture of sympathetic and parasympathetic nerves, little information on its composite fibers is available. Using 10 donated elderly cadavers, we investigated in detail the topohistology of nerve fibers in the posterior part of the periprostatic region in males and the infero-anterior part of the paracolpium in females. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were used as parasympathetic nerve markers, and tyrosine hydroxylase (TH) was used as a marker of sympathetic nerves. In the region examined, nNOS-positive nerves (containing nNOS-positive fibers) were consistently predominant numerically. All fibers positive for these markers appeared to be thin, unmyelinated fibers. Accordingly, the pelvic plexus branches were classified into 5 types: triple-positive mixed nerves (nNOS+, VIP+, TH+, thick myelinated fibers + or -); double-positive mixed nerves (nNOS+, VIP-, TH+, thick myelinated fibers + or -); nerves in arterial walls (nNOS-, VIP+, TH+, thick myelinated fibers-); non-parasympathetic nerves (nNOS-, VIP-, TH+, thick myelinated fibers + or -); (although rare) pure sensory nerve candidates (nNOS-, VIP-, TH-, thick myelinated fibers+). Triple-positive nerves were 5-6 times more numerous in the paracolpium than in the periprostatic region. Usually, the parasympathetic nerve fibers did not occupy a specific site in a nerve, and were intermingled with sympathetic fibers. This morphology might be the result of an "incidentally" adopted nerve fiber route, rather than a target-specific pathway. PMID:24693483

  8. Sympathetic preganglionic efferent and afferent neurons mediated by the greater splanchnic nerve in rabbit

    NASA Technical Reports Server (NTRS)

    Torigoe, Yasuhiro; Cernucan, Roxana D.; Nishimoto, Jo Ann S.; Blanks, Robert H. I.

    1985-01-01

    As a part of the study of the vestibular-autonomic pathways involved in motion sickness, the location and the morphology of preganglionic sympathetic neurons (PSNs) projecting via the greater splanchnic nerve were examined. Retrograde labeling of neurons was obtained by application of horseradish peroxidase to the cut end of the greater splanchnic nerve. Labeled PSNs were found, ipsilaterally, within the T1 to T11 spinal cord segments, with the highest density of neurons in T6. Most PSNs were located within the intermediolateral column, but a significant portion also occurred within the lateral funiculus, the intercalated region, and the central autonomic area; the proportion of labeling between the four regions depended on the spinal cord segment.

  9. Performance analysis of stationary and discrete wavelet transform for action potential detection from sympathetic nerve recordings in humans.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Shoemaker, J Kevin

    2008-01-01

    Accurate investigation of the sympathetic nervous system is important in the diagnosis and study of various autonomic and cardiovascular control and disorders. Sympathetic function associated with blood pressure regulation in humans can be evaluated by recording muscle sympathetic nerve activity (MSNA), which is characterised by synchronous neuronal discharges separated by periods of neural silence dominated by colored gaussian noise. In this paper two common methods for detecting filtered action potential in MSNA recordings is compared. These methods are based on stationary wavelet transform (SWT) and discrete wavelet transform (DWT). The performance analysis are evaluated using simulated MSNA using templates extracted from real MSNA recorded from three healthy subjects.

  10. The importance of the selection of appropriate reference genes for gene expression profiling in adrenal medulla or sympathetic ganglia of spontaneously hypertensive rat.

    PubMed

    Vavřínová, A; Behuliak, M; Zicha, J

    2016-07-18

    Catecholaminergic system plays an important role in hypertension development. The available results on mRNA expression of catecholaminergic system genes in spontaneously hypertensive rats (SHR) are often contradictory. One of the possible causes might be the use of various reference genes as internal controls. In the present study, we searched for suitable reference genes in adrenal medulla or sympathetic ganglia of SHR and Wistar-Kyoto (WKY) rats, which would enable reliable comparison of mRNA expression between these two strains. The mRNA expression was measured by quantitative real-time PCR in adrenal medulla and superior cervical ganglia of 4-week-old or 24-week-old SHR and WKY rats. We evaluated 12 reference genes by three software tools (Normfinder, BestKeeper, geNorm) and compared them for the standardization of mRNA expression. Combination of reference genes Hprt1 and Ywhaz in adrenal medulla and Gapdh and 18S in sympathetic ganglia were chosen as the best ones. 18S was found as applicable reference gene in both tissues. We found many alterations in expression of catecholaminergic system genes in adrenal medulla and sympathetic ganglia of SHR. The usage of the most or the least stable reference gene as internal control changed results moderately in sympathetic ganglia but seriously in adrenal medulla. For example, tyrosine hydroxylase (Th) gene was underexpressed in adrenal medulla of adult SHR using the appropriate reference gene but unchanged after the standardization to the least stable reference gene. Our results indicate the importance of appropriate internal control. The suitability of reference genes should be checked again in the case of change in experimental conditions.

  11. Effect of facial cooling and cold air inhalation on sympathetic nerve activity in men.

    PubMed

    Heindl, Silke; Struck, Jan; Wellhöner, Peter; Sayk, Friedhelm; Dodt, Christoph

    2004-08-20

    In nine healthy subjects, cold stimuli were administered to the forehead and hand, to the oral and nasal cavities via ice cubes and to the bronchial system via inhalation of cold air (-25 degrees C). Blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) from the peroneal nerve were recorded. MSNA expressed as total activity increased during cold air inhalation, cooling of the forehead (P < 0.001, ANOVA), hand and mouth (P < or = 0.05), paralleled by a rise in blood pressure during cold air inhalation and cooling of the forehead and hand (P < 0.01). Cooling of the forehead provoked a faster increase of MSNA expressed as total activity (P < 0.05) and higher levels of diastolic blood pressure (P = 0.05) compared with cooling of the hand. Bradycardia was observed only during cooling of the nasal cavity (P < 0.001) and the forehead (P < 0.05). It is concluded that cooling of the skin and mucous membranes of the tracheobronchial tract elicits sympathetically mediated hemodynamic adaptations, probably via stimulation of cold-sensitive afferents. PMID:15351305

  12. Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension

    PubMed Central

    Grassi, Guido; Seravalle, Gino; Trevano, Fosca Quarti; Spaziani, Domenico; Scalise, Filippo; Auguadro, Carla; Pizzini, Patrizia; Tripepi, Giovanni; D’Arrigo, Graziella; Mallamaci, Francesca; Mancia, Giuseppe; Zoccali, Carmine

    2015-01-01

    Background and objectives The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown. Design, setting, participants, & measurements In this longitudinal study (follow-up: 2 weeks–6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment. Results Time-integrated changes in MSNAC after renal denervation ranged from –40.6% to 10% (average, –15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up. Conclusions In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition. PMID:26138262

  13. Comparison of sympathetic nerve responses to neck and forearm isometric exercise

    NASA Technical Reports Server (NTRS)

    Steele, S. L. Jr; Ray, C. A.

    2000-01-01

    PURPOSE: Although the autonomic and cardiovascular responses to arm and leg exercise have been studied, the sympathetic adjustments to exercise of the neck have not. The purpose of the present study was twofold: 1) to determine sympathetic and cardiovascular responses to isometric contractions of the neck extensors and 2) to compare sympathetic and cardiovascular responses to isometric exercise of the neck and forearm. METHODS: Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate were measured in nine healthy subjects while performing isometric neck extension (INE) and isometric handgrip (IHG) in the prone position. After a 3-min baseline period, subjects performed three intensities of INE for 2.5 min each: 1) unloaded (supporting head alone), 2) 10% maximal voluntary contraction (MVC), and 3) 30% MVC, then subjects performed two intensities (10% and 30% MVC) of IHG for 2.5 min. RESULTS: Supporting the head by itself did not significantly change any of the variables. During [NE, MAP significantly increased by 10 +/- 2 and 31 +/- 4 mm Hg and MSNA increased by 67 +/- 46 and 168 +/- 36 units/30 s for 10% and 30% MVC, respectively. IHG and INE evoked similar responses at 10% MVC, but IHG elicited higher peak MAP and MSNA at 30% MVC (37 +/- 7 mm Hg (P < 0.05) and 300 +/- 48 units/30 s (P < 0.01) for IHG, respectively). CONCLUSIONS: The data indicate that INE can elicit marked increases in MSNA and cardiovascular responses but that it evokes lower peak responses as compared to IHG. We speculate that possible differences in muscle fiber type composition, muscle mass, and/or muscle architecture of the neck and forearm are responsible for these differences in peak responses.

  14. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen.

    PubMed

    Shi, Zhigang; Brooks, Virginia L

    2015-04-01

    Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR in ovariectomized rats, but its effects were normalized with 4 days of oestrogen treatment. Bilateral nanoinjection of SHU9119 into the paraventricular nucleus of the hypothalamus (PVN), to block α-melanocyte-stimulating hormone (α-MSH) type 3 and 4 receptors, decreased LSNA in leptin-treated pro-oestrus but not dioestrus rats. Unlike leptin, i.c.v. insulin infusion increased basal and baroreflex control of LSNA and HR similarly in pro-oestrus and dioestrus rats; these responses did not differ from those in male rats. We conclude that, in female rats, leptin's stimulatory effects on SNA are differentially enhanced by oestrogen, at least in part via an increase in α-MSH activity in the PVN. These data further suggest that the actions of leptin and insulin to increase the activity of various sympathetic nerves occur via different neuronal pathways or cellular mechanisms. These results may explain the poor correlation in females of SNA with adiposity, or of MAP with leptin. PMID:25398524

  15. Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice

    PubMed Central

    2012-01-01

    Introduction Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sprouting; however, neuroplasticity is generally thought to be greater in young versus old nerves. Here we explore whether sensory and sympathetic nerve fibers can undergo a significant ectopic nerve remodeling in the painful arthritic knee joint of geriatric mice. Methods Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic nerve fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), and growth-associated protein 43 (GAP43; nerve fibers undergoing sprouting). Results At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ nerve fibers in the synovium and periosteum. Conclusions Sensory and sympathetic nerve fibers that innervate the aged knee joint clearly maintain the capacity for robust

  16. The Involvement of Parasympathetic and Sympathetic Nerve in the Inflammatory Reflex.

    PubMed

    Pereira, Mariana Rodrigues; Leite, Paulo Emílio Corrêa

    2016-09-01

    Production of inflammatory cytokines plays important roles in the response against tissue injury and in host defense. Alterations in the production of inflammatory cytokines may cause local or systemic inflammatory imbalance, culminating in organ failure or lethal systemic inflammation. The cholinergic anti-inflammatory pathway has been implicated as an important mechanism to regulate inflammation of targeted tissue. In this review, we discuss important advances, conflicting and controversial findings regarding the involvement of parasympathetic vagus and sympathetic splenic nerve through acetylcholine (ACh) release and α7 nicotinic acetylcholine receptor (nAChRα7) activation in the spleen. In addition, we address the involvement of cholinergic control of inflammation in other organs innerved by the vagus nerve such as gut, liver, kidney and lung, and independent of parasympathetic innervations such as skin and skeletal muscle. Then, other structures and mechanisms independent of vagus or splenic nerve may be involved in this process, such as local cells and motor neurons producing ACh. Altogether, the convergence of these findings may contribute to current anti-inflammatory strategies involving selective drug-targeting and electrical nerve stimulation. J. Cell. Physiol. 231: 1862-1869, 2016. © 2016 Wiley Periodicals, Inc.

  17. Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction.

    PubMed

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Gao, Erhe; Ebert, Steven N; Dorn, Gerald W; Koch, Walter J

    2010-05-21

    Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells of the adrenal gland, we crossed PNMTCre mice, expressing Cre recombinase under the chromaffin cell-specific phenylethanolamine N-methyltransferase (PNMT) gene promoter, with floxedGRK2 mice. After confirming a significant ( approximately 50%) reduction of adrenal GRK2 mRNA and protein levels, the PNMT-driven GRK2 knock-out (KO) offspring underwent myocardial infarction (MI) to induce HF. At 4 weeks post-MI, plasma levels of both norepinephrine and epinephrine were reduced in PNMT-driven GRK2 KO, compared with control mice, suggesting markedly reduced post-MI sympathetic activation. This translated in PNMT-driven GRK2 KO mice into improved cardiac function and dimensions as well as amelioration of abnormal cardiac beta-adrenergic receptor signaling at 4 weeks post-MI. Thus, adrenal-targeted GRK2 gene KO decreases circulating CAs, leading to improved cardiac function and beta-adrenergic reserve in post-MI HF. GRK2 inhibition in the adrenal gland might represent a novel sympatholytic strategy that can aid in blocking HF progression.

  18. [Adrenalitis].

    PubMed

    Saeger, W

    2016-05-01

    Inflammation of the adrenal glands is caused by autoimmunopathies or infections and can induce adrenal insufficiency. Autoimmune lymphocytic adrenalitis is often combined with other autoimmune diseases and the most frequent cause of Addison's disease; however, it only becomes clinically apparent when more than 90 % of the adrenal cortex has been destroyed. Histological features are characterized by lymphoplasmacytic inflammation leading to an increased destruction of adrenocortical tissue but less severe courses can also occur. The second most frequent form of adrenalitis is adrenal tuberculosis, showing typical granulomatous findings that are nearly always caused by spreading from a tuberculous pulmonary focus. Other bacterial as well as viral infections, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and others, generally affect the adrenal glands only in patients with immunodeficiency disorders. In these infections, the adrenal cortex and medulla are frequently involved to roughly the same extent. Although surgical specimens from inflammatory adrenal lesions are extremely rare, the various forms of adrenalitis play an important role in the post-mortem examination of the adrenal glands for clarification of unclear causes of death (e.g. death during an Addisonian crisis). PMID:27099224

  19. Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans.

    PubMed Central

    Vollenweider, P; Tappy, L; Randin, D; Schneiter, P; Jéquier, E; Nicod, P; Scherrer, U

    1993-01-01

    Euglycemic hyperinsulinemia evokes both sympathetic activation and vasodilation in skeletal muscle, but the mechanism remains unknown. To determine whether insulin per se or insulin-induced stimulation of carbohydrate metabolism is the main excitatory stimulus, we performed, in six healthy lean subjects, simultaneous microneurographic recordings of muscle sympathetic nerve activity, plethysmographic measurements of calf blood flow, and calorimetric determinations of carbohydrate oxidation rate. Measurements were made during 2 h of: (a) insulin/glucose infusion (hyperinsulinemic [6 pmol/kg per min] euglycemic clamp), (b) exogenous glucose infusion at a rate matched to that attained during protocol a, and (c) exogenous fructose infusion at the same rate as for glucose infusion in protocol b. For a comparable rise in carbohydrate oxidation, insulin/glucose infusion that resulted in twofold greater increases in plasma insulin concentrations than did glucose infusion alone, evoked twofold greater increases in both muscle sympathetic nerve activity and calf blood flow. Fructose infusion, which increased carbohydrate oxidation comparably, but had only a minor effect on insulinemia, did not stimulate either muscle sympathetic nerve activity or calf blood flow. These observations suggest that in humans hyperinsulinemia per se, rather than insulin-induced stimulation of carbohydrate metabolism, is the main mechanism that triggers both sympathetic activation and vasodilation in skeletal muscle. PMID:8325979

  20. Sympathetic sprouting near sensory neurons after nerve injury occurs preferentially on spontaneously active cells and is reduced by early nerve block

    PubMed Central

    Xie, Wenrui; Strong, Judith Ann; Li, Huiqing; Zhang, Jun-Ming

    2006-01-01

    Some chronic pain conditions are maintained or enhanced by sympathetic activity. In animal models of pathological pain, abnormal sprouting of sympathetic fibers around large- and medium-size sensory neurons is observed in dorsal root ganglia (DRG). Large and medium size cells are also more likely to be spontaneously active, suggesting that sprouting may be related to neuron activity. We previously showed that sprouting could be reduced by systemic or locally applied lidocaine. In the complete sciatic nerve transection model in rats, spontaneous activity initially originates in the injury site; later, the DRG become the major source of spontaneous activity. In this study, spontaneous activity reaching the DRG soma was reduced by early nerve blockade (local perfusion of the transected nerve with TTX for the first 7 days after injury). This significantly reduced sympathetic sprouting. Conversely, increasing spontaneous activity by local nerve perfusion with K+ channel blockers increased sprouting. The hyperexcitability and spontaneous activity of DRG neurons observed in this model were also significantly reduced by early nerve blockade. These effects of early nerve blockade on sprouting, excitability, and spontaneous activity were all observed 4 to 5 weeks after the end of early nerve blockade, indicating that the early period of spontaneous activity in the injured nerve is critical for establishing the more long-lasting pathologies observed in the DRG. Individual spontaneously active neurons, labeled with fluorescent dye, were 5–6 times more likely than quiescent cells to be co-localized with sympathetic fibers, suggesting a highly localized correlation of activity and sprouting. PMID:17065247

  1. Sympathetic nerve fibers sprout into rat odontoblast layer, but not into dentinal tubules, in response to cavity preparation.

    PubMed

    Shimeno, Yoichi; Sugawara, Yumiko; Iikubo, Masahiro; Shoji, Noriaki; Sasano, Takashi

    2008-04-11

    This study was designed to determine if sympathetic nerve fibers exist in dentinal tubules in rat normal dental pulp, and if they sprout into the dentinal tubules in response to artificial cavity preparation in dentin. Sympathetic nerve fibers in rat molar dental pulp were labeled using an anterograde axonal transport technique involving injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the superior cervical ganglion (SCG). They were then observed using light and electron microscopes. In normal dental pulp (control), scattered WGA-HRP reaction products were observed in unmyelinated nerve endings in the odontoblast layer and subodontoblastic region. In injured pulp 3 weeks after cavity preparation, reaction products were about 1.8-times more plentiful in the above areas (versus control pulp). However, no labeled nerve fibers were observed in the dentinal tubules in either control or injured dental pulp. These results indicate that although sympathetic nerve fibers do indeed sprout in rat dental pulp in response to cavity preparation, they do not penetrate into the dentinal tubules in which postganglionic nerve endings derived from the SCG were not originally present.

  2. L-Ornithine intake affects sympathetic nerve outflows and reduces body weight and food intake in rats.

    PubMed

    Konishi, Yuuki; Koosaka, Yasutaka; Maruyama, Ryuutaro; Imanishi, Kazuki; Kasahara, Kazuaki; Matsuda, Ai; Akiduki, Saori; Hishida, Yukihiro; Kurata, Yasutaka; Shibamoto, Toshishige; Satomi, Jun; Tanida, Mamoru

    2015-02-01

    Ingesting the amino acid l-ornithine effectively improves lipid metabolism in humans, although it is unknown whether it affects the activities of autonomic nerves that supply the peripheral organs related to lipid metabolism, such as adipose tissues. Thus, we investigated the effects of l-ornithine ingestion on autonomic nerves that innervate adipose tissues and the feeding behaviors of rats. Intragastric injection of l-ornithine (2.5%) in urethane-anesthetized rats activated sympathetic nerve activity to white adipose tissue (WAT-SNA), and stimulated sympathetic nerve activity to brown adipose tissue (BAT-SNA). In addition, WAT-SNA responses to l-ornithine were abolished in rats with ablated abdominal vagal nerves. l-ornithine ingestion for 9 weeks also significantly reduced rats' body weight, food intake, and abdominal fat weight. Proopiomelanocortin (POMC) levels in the hypothalamus and uncoupling protein 1 (UCP1) levels in brown adipose tissue were significantly increased in rats that ingested 2.5% l-ornithine for 9 weeks. These results suggested that ingested l-ornithine was taken up in the gastrointestinal organs and stimulated afferent vagal nerves and activated the central nervous system. Subsequently, increased hypothalamic POMC activated sympathetic neurotransmission to adipose tissues and accelerated energy expenditure. PMID:25526897

  3. Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients.

    PubMed

    Metzler-Wilson, Kristen; Toma, Kumika; Sammons, Dawn L; Mann, Sarah; Jurovcik, Andrew J; Demidova, Olga; Wilson, Thad E

    2015-09-01

    Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2-min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50°C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux·100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 ± 0.02 vs. control 0.10 ± 0.01 mg·cm(-2)·min(-1), P < 0.05). HR and MAP changes were not different between groups during sympathoexcitatory stressors or local heating. SSNA during early mental (32 ± 9 and 9 ± 4% increase) and physical (25 ± 4 and 5 ± 1% increase, rosacea and controls, respectively) stress was augmented in rosacea (both P < 0.05). Heat stress induced more rapid sweating and cutaneous vasodilation onset in rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component.

  4. Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients.

    PubMed

    Metzler-Wilson, Kristen; Toma, Kumika; Sammons, Dawn L; Mann, Sarah; Jurovcik, Andrew J; Demidova, Olga; Wilson, Thad E

    2015-09-01

    Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2-min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50°C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux·100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 ± 0.02 vs. control 0.10 ± 0.01 mg·cm(-2)·min(-1), P < 0.05). HR and MAP changes were not different between groups during sympathoexcitatory stressors or local heating. SSNA during early mental (32 ± 9 and 9 ± 4% increase) and physical (25 ± 4 and 5 ± 1% increase, rosacea and controls, respectively) stress was augmented in rosacea (both P < 0.05). Heat stress induced more rapid sweating and cutaneous vasodilation onset in rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component. PMID:26133800

  5. Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients

    PubMed Central

    Metzler-Wilson, Kristen; Toma, Kumika; Sammons, Dawn L.; Mann, Sarah; Jurovcik, Andrew J.; Demidova, Olga

    2015-01-01

    Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2-min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50°C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux·100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 ± 0.02 vs. control 0.10 ± 0.01 mg·cm−2·min−1, P < 0.05). HR and MAP changes were not different between groups during sympathoexcitatory stressors or local heating. SSNA during early mental (32 ± 9 and 9 ± 4% increase) and physical (25 ± 4 and 5 ± 1% increase, rosacea and controls, respectively) stress was augmented in rosacea (both P < 0.05). Heat stress induced more rapid sweating and cutaneous vasodilation onset in rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component. PMID:26133800

  6. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    PubMed Central

    Salman, Ibrahim M.; Sarma Kandukuri, Divya; Harrison, Joanne L.; Hildreth, Cara M.; Phillips, Jacqueline K.

    2015-01-01

    Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n = 16) were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2) and central chemoreflex (hypercapnia: 7% CO2) activation and acute stress (open-field exposure), were measured. As indicators of renal function, urinary protein (UPro) and creatinine (UCr) levels were assessed. LPK rats had higher resting RSNA (1.2 ± 0.1 vs. 0.6 ± 0.1 μV, p < 0.05) and MAP (151 ± 8 vs. 97 ± 2 mmHg, p < 0.05) compared to Lewis. MAP was negatively correlated with UCr (r = −0.80, p = 0.002) and positively correlated with RSNA (r = 0.66, p = 0.014), with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p < 0.05). This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways. PMID:26300784

  7. Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans

    NASA Technical Reports Server (NTRS)

    Doerzbacher, K. J.; Ray, C. A.

    2001-01-01

    Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.

  8. Dissociation of muscle sympathetic nerve activity and leg vascular resistance in humans

    NASA Technical Reports Server (NTRS)

    Shoemaker, J. K.; Herr, M. D.; Sinoway, L. I.

    2000-01-01

    We examined the hypothesis that the increase in inactive leg vascular resistance during forearm metaboreflex activation is dissociated from muscle sympathetic nerve activity (MSNA). MSNA (microneurography), femoral artery mean blood velocity (FAMBV, Doppler), mean arterial pressure (MAP), and heart rate (HR) were assessed during fatiguing static handgrip exercise (SHG, 2 min) followed by posthandgrip ischemia (PHI, 2 min). Whereas both MAP and MSNA increase during SHG, the transition from SHG to PHI is characterized by a transient reduction in MAP but sustained elevation in MSNA, facilitating separation of these factors in vivo. Femoral artery vascular resistance (FAVR) was calculated (MAP/MBV). MSNA increased by 59 +/- 20% above baseline during SHG (P < 0.05) and was 58 +/- 18 and 78 +/- 18% above baseline at 10 and 20 s of PHI, respectively (P < 0.05 vs. baseline). Compared with baseline, FAVR increased 51 +/- 22% during SHG (P < 0.0001) but returned to baseline levels during the first 30 s of PHI, reflecting the changes in MAP (P < 0.005) and not MSNA. It was concluded that control of leg muscle vascular resistance is sensitive to changes in arterial pressure and can be dissociated from sympathetic factors.

  9. Auditory stimulation affects renal sympathetic nerve activity and blood pressure in rats.

    PubMed

    Nakamura, Takuo; Tanida, Mamoru; Niijima, Akira; Hibino, Hiroshi; Shen, Jiao; Nagai, Katsuya

    2007-04-12

    Here, we examined the effects of auditory stimulation at 50 dB with white noise (WN) or music (Traeumerei [TM] by Schumann or Etude by Chopin) on renal sympathetic nerve activity (RSNA) and BP in urethane-anesthetized rats. Auditory stimulation with TM, but not with WN or the Etude, significantly decreased RSNA and BP. Complete bilateral destruction of the cochleae and bilateral lesions of the auditory cortex (AuC) eliminated the effects of TM stimulation on RSNA and BP, but bilateral lesions of primary somatosensory cortex (S1C) had no effect. Bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) or intracerebral administration of thioperamide, a histaminergic H3 receptor antagonist, also abolished TM-induced decreases in RSNA and BP. These findings suggest that exposure to music can decrease RSNA and BP through the auditory pathway, histaminergic neurons, and the SCN.

  10. Detection and classification of raw action potential patterns in human Muscle Sympathetic Nerve Activity.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Shoemaker, J K

    2008-01-01

    The Muscle Sympathetic Nerve Activity (MSNA) consists of synchronous neural discharges separated by periods of neural silence dominated by heavy background noise. During measurement with electrodes, the raw MSNA signal is amplified, band-pass filtered, rectified and integrated. This integration process removes much neurophysiological information. In this paper a method for detecting a raw action potential (before the pre-amplifier) and filtered action potential (after the band-pass filter) is presented. This method is based on stationary wavelet transform (SWT) and a peak detection algorithm. Also, the detected action potentials were clustered using the k-means method and the cluster averages were calculated. The action potential detector and classification algorithm are evaluated using real MSNA recorded from three healthy subjects.

  11. Whole body heat stress attenuates baroreflex control of muscle sympathetic nerve activity during postexercise muscle ischemia

    PubMed Central

    Cui, Jian; Shibasaki, Manabu; Davis, Scott L.; Low, David A.; Keller, David M.; Crandall, Craig G.

    2009-01-01

    Both whole body heat stress and stimulation of muscle metabolic receptors activate muscle sympathetic nerve activity (MSNA) through nonbaroreflex pathways. In addition to stimulating muscle metaboreceptors, exercise has the potential to increase internal temperature. Although we and others report that passive whole body heating does not alter the gain of the arterial baroreflex, it is unknown whether increased body temperature, often accompanying exercise, affects baroreflex function when muscle metaboreceptors are stimulated. This project tested the hypothesis that whole body heating alters the gain of baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate during muscle metaboreceptor stimulation engaged via postexercise muscle ischemia (PEMI). MSNA, blood pressure (BP, Finometer), and heart rate were recorded from 11 healthy volunteers. The volunteers performed isometric handgrip exercise until fatigue, followed by 2.5 min of PEMI. During PEMI, BP was acutely reduced and then raised pharmacologically using the modified Oxford technique. This protocol was repeated two to three times when volunteers were normothermic, and again during heat stress (increase core temperature ∼ 0.7°C) conditions. The slope of the relationship between MSNA and BP during PEMI was less negative (i.e., decreased baroreflex gain) during whole body heating when compared with the normothermic condition (−4.34 ± 0.40 to −3.57 ± 0.31 units·beat−1·mmHg−1, respectively; P = 0.015). The gain of baroreflex control of heart rate during PEMI was also decreased during whole body heating (P < 0.001). These findings indicate that whole body heat stress reduces baroreflex control of MSNA and heart rate during muscle metaboreceptor stimulation. PMID:19213933

  12. Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans.

    PubMed

    Young, Colin N; Deo, Shekhar H; Chaudhary, Kunal; Thyfault, John P; Fadel, Paul J

    2010-09-15

    Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (34 ± 6 uIU ml(1); P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex-MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: 3.29 ± 0.54 baseline vs. 5.64 ± 0.67 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (42 ± 6 μIU ml(1); P < 0.05), while glucose was maintained constant, arterial baroreflex-MSNA gain was similarly enhanced (e.g. burst incidence gain: 2.44 ± 0.29 baseline vs. 4.74 ± 0.71 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex-MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA.

  13. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity.

    PubMed

    Tiradentes, R V; Pires, J G P; Silva, N F; Ramage, A G; Santuzzi, C H; Futuro Neto, H A

    2014-07-01

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33 ± 4.7 and -31 ± 5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35 ± 5.4 and -31 ± 5.5%, respectively, with an increase in blood pressure +26.3 ± 2.5; 3 mg/kg sertraline reduced RSNA by -59.4 ± 8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central. PMID:25003632

  14. Characteristics of renal sympathetic nerve single units in rabbits with angiotensin-induced hypertension.

    PubMed

    Burke, Sandra L; Lukoshkova, Elena V; Head, Geoffrey A

    2016-01-01

    We examined the effect of chronic angiotensin (Ang II)-induced hypertension on activity of postganglionic renal sympathetic units to determine whether altered whole renal nerve activity is due to recruitment or changes in firing frequency. Rabbits were treated with a low (20 ng kg(-1) min(-1), 8 weeks) or high dose (50 ng kg(-1) min(-1), 4 weeks) of Ang II before the experiment under chloralose-urethane anaesthesia. Spontaneously active units were detected from multiunit recordings using an algorithm that separated units by action potential shape using templates that matched spikes within a prescribed standard deviation. Multiunit sympathetic nerve activity was 40% higher in rabbits treated with low-dose Ang II than in sham (P = 0.012) but not different in high-dose Ang II. Resting firing frequency was similar in sham rabbits (1.00 ± 0.09 spikes s(-1), n = 144) and in those treated with high-dose Ang II (1.10 ± 0.08 spikes s(-1), n = 112) but was lower with low-dose Ang II (0.65 ± 0.08 spikes s(-1), n = 149, P < 0.05). Unit firing rhythmicity was linked to the cardiac cycle and was similar in sham and low-dose Ang II groups but 29-32% lower in rabbits treated with high-dose Ang II (P < 0.001). Cardiac linkage followed a similar pattern during hypoxia. All units showed baroreceptor dependency. Baroreflex gain and range were reduced and curves shifted to the right in Ang II groups. Firing frequency during hypoxia increased by +39% in low-dose Ang II and +82% in shams, but the greatest increase was in the high-dose Ang II group (+103%, P(dose) = 0.001). Responses to hypercapnia were similar in all groups. Increases in sympathetic outflow in hypertension caused by low-dose chronic Ang II administration are due to recruitment of neurons, but high-dose Ang II increases firing frequency in response to chemoreceptor stimuli independently of the arterial baroreceptors. PMID:26467849

  15. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen

    PubMed Central

    Shi, Zhigang; Brooks, Virginia L

    2015-01-01

    Key points Leptin increases sympathetic nerve activity (SNA) in males, which contributes to obesity-induced hypertension; however, whether leptin is equally effective in females is unknown. We report that leptin does increase SNA and heart rate in female rats; however, for lumbar and renal SNA, this action is only evident in pro-oestrus and in oestrogen-treated ovariectomized rats, but not in ovariectomized or dioestrus rats. Leptin increases SNA and heart rate similarly in male and pro-oestrus female rats; however, leptin increases arterial pressure only in males. Blockade of MC3/4 receptors in the paraventricular nucleus (PVN) with SHU9119 decreases SNA in leptin-treated pro-oestrus rats, suggesting that leptin increases SNA in part by increasing α-melanocyte-stimulating hormone drive of PVN presympathetic neurons. Our data establish sex differences in leptin's effects to increase SNA and arterial pressure, which emphasizes the need for enhanced recognition and investigation of sex differences in obesity-induced sympathoexcitation and hypertension. Abstract Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR

  16. Contributions of Central Command and Muscle Feedback to Sympathetic Nerve Activity in Contracting Human Skeletal Muscle

    PubMed Central

    Boulton, Daniel; Taylor, Chloe E.; Macefield, Vaughan G.; Green, Simon

    2016-01-01

    During voluntary contractions, muscle sympathetic nerve activity (MSNA) to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-min isometric dorsiflexion contractions (left leg) separated by 2-min rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5–10% of maximum). MSNA was recorded continuously (microneurography) from the left peroneal nerve and quantified from cardiac-synchronized, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34% (P < 0.01) during voluntary contractions but did not change significantly during electrically-evoked contractions (−8 ± 12%, P > 0.05). MSNA analyzed at 15-s intervals revealed that this effect of voluntary contraction appeared 15–30 s after contraction onset (P < 0.01), remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction. PMID:27242537

  17. Vestibular modulation of muscle sympathetic nerve activity during sinusoidal linear acceleration in supine humans

    PubMed Central

    Hammam, Elie; Bolton, Philip S.; Kwok, Kenny; Macefield, Vaughan G.

    2014-01-01

    The utricle and saccular components of the vestibular apparatus preferentially detect linear displacements of the head in the horizontal and vertical planes, respectively. We previously showed that sinusoidal linear acceleration in the horizontal plane of seated humans causes a pronounced modulation of muscle sympathetic nerve activity (MSNA), supporting a significant role for the utricular component of the otolithic organs in the control of blood pressure. Here we tested the hypothesis that the saccule can also play a role in blood pressure regulation by modulating lower limb MSNA. Oligounitary MSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve in 12 subjects, laying supine on a motorized platform with the head aligned with the longitudinal axis of the body. Slow sinusoidal linear accelerations-decelerations (peak acceleration ±4 mG) were applied in the rostrocaudal axis (which predominantly stimulates the saccule) and in the mediolateral axis (which also engages the utricle) at 0.08 Hz. The modulation of MSNA in the rostrocaudal axis (29.4 ± 3.4%) was similar to that in the mediolateral axis (32.0 ± 3.9%), and comparable to that obtained by stimulation of the utricle alone in seated subjects with the head vertical. We conclude that both the saccular and utricular components of the otolithic organs play a role in the control of arterial pressure during postural challenges. PMID:25346657

  18. Contributions of Central Command and Muscle Feedback to Sympathetic Nerve Activity in Contracting Human Skeletal Muscle.

    PubMed

    Boulton, Daniel; Taylor, Chloe E; Macefield, Vaughan G; Green, Simon

    2016-01-01

    During voluntary contractions, muscle sympathetic nerve activity (MSNA) to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-min isometric dorsiflexion contractions (left leg) separated by 2-min rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10% of maximum). MSNA was recorded continuously (microneurography) from the left peroneal nerve and quantified from cardiac-synchronized, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34% (P < 0.01) during voluntary contractions but did not change significantly during electrically-evoked contractions (-8 ± 12%, P > 0.05). MSNA analyzed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01), remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction. PMID:27242537

  19. Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carrasco, D. I.

    2000-01-01

    The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.

  20. Alzheimer caregiver stress: basal natural killer cell activity, pituitary-adrenal cortical function, and sympathetic tone.

    PubMed

    Irwin, M; Hauger, R; Patterson, T L; Semple, S; Ziegler, M; Grant, I

    1997-01-01

    The association between Alzheimer caregiving and natural killer (NK) cell activity and basal plasma levels of adrenocorticotropic hormone (ACTH), cortisol, beta-endorphin, prolactin, epinephrine, norepinephrine, and neuropeptide Y was determined in 100 spousal Alzheimer caregivers and 33 age- and gender-comparable control volunteers upon intake into a study of the psychological and physiologic impact of caregiving. The relationship between these physiologic measures and individual characteristics such as age, gender, medical status, severity of stress, severity of depressive symptoms, and caregiver burden was tested. In addition, the association between NK activity and alterations of the neuroendocrine measures was investigated. As compared to controls, the Alzheimer caregivers had similar levels of NK activity and of basal plasma neuroendocrine hormones and sympathetic measures. While older age and male gender status were associated with increased levels of ACTH, neither medical caseness, severity of life stress, nor severity of depressive symptoms was associated with alterations in any of the multiple physiologic domains. Classification of Alzheimer caregiver burden identified caregivers who were mismatched in terms of the amount of care they were required to provide and the amount of respite time received. The mismatched caregivers had significantly higher basal plasma ACTH but no change in other physiological measures, as compared to non-mismatched caregivers. NK activity was negatively correlated with plasma levels of neuropeptide Y but not with any of the other neuroendocrine measures. Based on this cross-sectional evaluation of NK activity and neuroendocrine and sympathetic measures, we conclude that most Alzheimer caregivers do not show evidence of altered basal physiology.

  1. 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.

  2. Arterial baroreflex control of muscle sympathetic nerve activity under orthostatic stress in humans.

    PubMed

    Ichinose, Masashi; Nishiyasu, Takeshi

    2012-01-01

    The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity's effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate (HR) are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR) and cardiopulmonary stretch receptors (cardiopulmonary baroreflex). In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA) while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure, and HR responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of mean arterial blood pressure (MAP) and greater HR response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.

  3. Effects of lower body positive pressure on muscle sympathetic nerve activity response [correction of respopnse] to head-up tilt.

    PubMed

    Fu, Q; Iwase, S; Niimi, Y; Kamiya, A; Kawanokuchi, J; Cui, J; Mano, T

    2001-07-01

    The benefits of lower body positive pressure (LBPP) are generally accepted for clinical treatment in medical emergencies caused by massive bleeding to maintain the systemic blood pressure. They are also used by NASA post spaceflight for preventing orthostatic hypotension in the astronauts. However, controversy still exists concerning the mechanisms underlying LBPP benefits. The purpose of this study was to test the hypothesis that the baroreflex-mediated enhancement in sympathetic activity would be attenuated by LBPP during an orthostatic challenge in humans. Specifically, we studied 1) the sympathetic activity responses by the microneurographic technique, using direct intraneural measurement of muscle sympathetic nerve activity (MSNA); and 2) the contributions of preload and afterload to the chances in MSNA response during orthostasis on application of LBPP. To accomplish these issues, MSNA was recorded microneurographically along with noninvasive measurement of the cardiovascular variables in all the subjects during exposure to a 70 degrees HUT with 30-mm Hg LBPP.

  4. Increased Muscle Sympathetic Nerve Activity and Impaired Executive Performance Capacity in Obstructive Sleep Apnea

    PubMed Central

    Goya, Thiago T.; Silva, Rosyvaldo F.; Guerra, Renan S.; Lima, Marta F.; Barbosa, Eline R.F.; Cunha, Paulo Jannuzzi; Lobo, Denise M.L.; Buchpiguel, Carlos A.; Busatto-Filho, Geraldo; Negrão, Carlos E.; Lorenzi-Filho, Geraldo; Ueno-Pardi, Linda M.

    2016-01-01

    Study Objectives: To investigate muscle sympathetic nerve activity (MSNA) response and executive performance during mental stress in obstructive sleep apnea (OSA). Methods: Individuals with no other comorbidities (age = 52 ± 1 y, body mass index = 29 ± 0.4, kg/m2) were divided into two groups: (1) control (n = 15) and (2) untreated OSA (n = 20) defined by polysomnography. Mini-Mental State of Examination (MMSE) and Inteligence quocient (IQ) were assessed. Heart rate (HR), blood pressure (BP), and MSNA (microneurography) were measured at baseline and during 3 min of the Stroop Color Word Test (SCWT). Sustained attention and inhibitory control were assessed by the number of correct answers and errors during SCWT. Results: Control and OSA groups (apnea-hypopnea index, AHI = 8 ± 1 and 47 ± 1 events/h, respectively) were similar in age, MMSE, and IQ. Baseline HR and BP were similar and increased similarly during SCWT in control and OSA groups. In contrast, baseline MSNA was higher in OSA compared to controls. Moreover, MSNA significantly increased in the third minute of SCWT in OSA, but remained unchanged in controls (P < 0.05). The number of correct answers was lower and the number of errors was significantly higher during the second and third minutes of SCWT in the OSA group (P < 0.05). There was a significant correlation (P < 0.01) between the number of errors in the third minute of SCWT with AHI (r = 0.59), arousal index (r = 0.55), and minimum O2 saturation (r = −0.57). Conclusions: As compared to controls, MSNA is increased in patients with OSA at rest, and further significant MSNA increments and worse executive performance are seen during mental stress. Clinical Trial Registration: URL: http://www.clinicaltrials.gov, registration number: NCT002289625. Citation: Goya TT, Silva RF, Guerra RS, Lima MF, Barbosa ER, Cunha PJ, Lobo DM, Buchpiguel CA, Busatto-Filho G, Negrão CE, Lorenzi-Filho G, Ueno-Pardi LM. Increased muscle sympathetic nerve activity and

  5. Perfusion of isolated carotid sinus with hydrogen sulfide attenuated the renal sympathetic nerve activity in anesthetized male rats.

    PubMed

    Guo, Q; Wu, Y; Xue, H; Xiao, L; Jin, S; Wang, R

    2016-07-18

    The purpose of the present study was to define the indirect central effect of hydrogen sulfide (H(2)S) on baroreflex control of sympathetic outflow. Perfusing the isolated carotid sinus with sodium hydrosulfide (NaHS), a H(2)S donor, the effect of H(2)S was measured by recording changes of renal sympathetic nerve activity (RSNA) in anesthetized male rats. Perfusion of isolated carotid sinus with NaHS (25, 50, 100 micromol/l) dose and time-dependently inhibited sympathetic outflow. Preconditioning of glibenclamide (20 micromol/l), a ATP-sensitive K(+) channels (K(ATP)) blocker, the above effect of NaHS was removed. With 1, 4-dihydro-2, 6-dimethyl-5-nitro-4-(2-[trifluoromethyl] phenyl) pyridine-3-carboxylic acid methyl ester (Bay K8644, 500 nmol/l) pretreatment, which is an agonist of L-calcium channels, the effect of NaHS was eliminated. Perfusion of cystathionine gamma-lyase (CSE) inhibitor, DL-propargylglycine (PPG, 200 micromol/l), increased sympathetic outflow. The results show that exogenous H(2)S in the carotid sinus inhibits sympathetic outflow. The effect of H(2)S is attributed to opening K(ATP) channels and closing the L-calcium channels.

  6. Effects of chronic oestrogen treatment are not selective for uterine noradrenaline-containing sympathetic nerves: a transplantation study

    PubMed Central

    BRAUER, M. MONICA; CHAVEZ-GENARO, REBECA; LLODRA, JAIME; RICHERI, ANALIA; SCORZA, M. CECILIA

    2000-01-01

    Previous studies have shown that chronic administration of oestrogen during postnatal rat development dramatically reduces the total content of noradrenaline in the uterine horn, abolishes myometrial noradrenergic innervation and reduces noradrenaline-fluorescence intensity of intrauterine perivascular nerve fibres. In the present study we analysed if this response is due to a direct and selective effect of oestrogen on the uterine noradrenaline-containing sympathetic nerves, using the in oculo transplantation method. Small pieces of myometrium from prepubertal rats were transplanted into the anterior eye chamber of adult ovariectomised host rats. The effect of systemic chronic oestrogen treatment on the reinnervation of the transplants by noradrenaline-containing sympathetic fibres from the superior cervical ganglion was analysed on cryostat tissue sections processed by the glyoxylic acid technique. In addition, the innervation of the host iris was assessed histochemically and biochemically. The histology of the transplants and irises was examined in toluidine blue-stained semithin sections. These studies showed that after 5 wk in oculo, the overall size of the oestrogen-treated transplants was substantially larger than controls, and histology showed that this change was related to an increase in the size and number of smooth muscle cells within the transplant. Chronic oestrogen treatment did not provoke trophic changes in the irideal muscle. Histochemistry showed that control transplants had a rich noradrenergic innervation, associated with both myometrium and blood vessels. Conversely, in oestrogen-treated transplants only occasional fibres were recognised, showing a reduced NA fluorescence intensity. No changes in the pattern and density of innervation or in the total content of noradrenaline of the host irises were detected after chronic exposure to oestrogen. We interpreted these results to indicate that the effects of oestrogen on uterine noradrenaline

  7. Muscle pain perception and sympathetic nerve activity to exercise during opioid modulation

    NASA Technical Reports Server (NTRS)

    Cook, D. B.; O'Connor, P. J.; Ray, C. A.

    2000-01-01

    The purpose of this experiment was to examine the effects of the endogenous opioid system on forearm muscle pain and muscle sympathetic nerve activity (MSNA) during dynamic fatiguing exercise. Twelve college-age men (24 +/- 4 yr) performed graded (1-min stages; 30 contractions/min) handgrip to fatigue 1 h after the ingestion of either 60 mg codeine, 50 mg naltrexone, or placebo. Pain (0-10 scale) and exertion (0-10 and 6-20 scales) intensities were measured during the last 15 s of each minute of exercise and every 15 s during recovery. MSNA was measured continuously from the peroneal nerve in the left leg. Pain threshold occurred earlier [1.8 +/- 1, 2. 2 +/- 1, 2.2 +/- 1 J: codeine, naltrexone, and placebo, respectively] and was associated with a lower rating of perceived exertion (RPE) (2.7 +/- 2, 3.6 +/- 2, 3.8 +/- 2: codeine, naltrexone, and placebo, respectively) in the codeine condition compared with either the naltrexone or placebo conditions. There were no main effects (i.e., drugs) or interaction (i.e., drugs x time) for either forearm muscle pain or RPE during exercise [pain: F (2, 22) = 0.69, P = 0.51]. There was no effect of drug on MSNA, heart rate, or blood pressure during baseline, exercise, or recovery. Peak exercise MSNA responses were 21 +/- 1, 21 +/- 2.0, and 21 +/- 2.0 bursts/30 s for codeine, naltrexone, and placebo conditions, respectively. Peak mean arterial pressure responses were 135 +/- 4, 131 +/- 3, and 132 +/- 4 mmHg for codeine, naltrexone, and placebo conditions, respectively. It is concluded that neither 60 mg codeine nor 50 mg naltrexone has an effect on forearm muscle pain, exertion, or MSNA during high- intensity handgrip to fatigue.

  8. The Role of Lumbar Sympathetic Nerves in Regulation of Blood Flow to Skeletal Muscle during Anaphylactic Hypotension in Anesthetized Rats.

    PubMed

    Song, Jie; Tanida, Mamoru; Shibamoto, Toshishige; Zhang, Tao; Wang, Mofei; Kuda, Yuhichi; Kurata, Yasutaka

    2016-01-01

    During hypovolemic shock, skeletal muscle blood flow could be redistributed to vital organs via vasoconstriction in part evoked by activation of the innervating sympathetic nerve activity. However, it is not well known whether this mechanism operates during anaphylactic shock. We determined the femoral artery blood flow (FBF) and lumbar sympathetic nerve activity (LSNA) mainly regulating the hindquater muscle blood flow during anaphylactic hypotension in anesthetized rats. Anesthetized Sprague-Dawley rats were randomly allocated to the following groups (n = 7/group): (1) non-sensitized, (2) anaphylaxis, (3) anaphylaxis-lumbar sympathectomy (LS) and (4) anaphylaxis-sinoaortic denervation (SAD) groups. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen to the sensitized rats. The systemic arterial pressure (SAP), heart rate (HR), central venous pressure (CVP), FBF and LSNA were continuously measured. In the anaphylaxis group, LSNA and HR increased, while SAP and FBF decreased after antigen injection. In the anaphylaxis-SAD group, LSNA did not significantly change during the early phase, but the responses of SAP and FBF were similar to those in the anaphylaxis group. In the anaphylaxis-LS group, both FBF and SAP decreased similarly to the anaphylaxis group during anaphylactic hypotension. These results indicated that LSNA increased via baroreceptor reflex, but this sympathoexcitation or LS did not affect antigen-induced decreases in FBF or SAP. Lumbar sympathetic nerves are not involved in regulation of the blood flow to the hindlimb or systemic blood pressure during anaphylactic hypotension in anesthetized rats. PMID:26998924

  9. Single-Unit Muscle Sympathetic Nerve Activity Reflects Sleep Apnea Severity, Especially in Severe Obstructive Sleep Apnea Patients

    PubMed Central

    Hamaoka, Takuto; Murai, Hisayoshi; Kaneko, Shuichi; Usui, Soichiro; Okabe, Yoshitaka; Tokuhisa, Hideki; Kato, Takeshi; Furusho, Hiroshi; Sugiyama, Yu; Nakatsumi, Yasuto; Takata, Shigeo; Takamura, Masayuki

    2016-01-01

    Obstructive sleep apnea syndrome (OSAS) is associated with augmented sympathetic nerve activity, as assessed by multi-unit muscle sympathetic nerve activity (MSNA). However, it is still unclear whether single-unit MSNA is a better reflection of sleep apnea severity according to the apnea-hypopnea index (AHI). One hundred and two OSAS patients underwent full polysomnography and single- and multi-unit MSNA measurements. Univariate and multivariate regression analysis were performed to determine which parameters correlated with OSAS severity, which was defined by the AHI. Single- and multi-unit MSNA were significantly and positively correlated with AHI severity. The AHI was also significantly correlated with multi-unit MSNA burst frequency (r = 0.437, p < 0.0001) and single-unit MSNA spike frequency (r = 0.632, p < 0.0001). Multivariable analysis revealed that SF was correlated most significantly with AHI (T = 7.27, p < 0.0001). The distributions of multiple single-unit spikes per one cardiac interval did not differ between patients with an AHI of <30 and those with and AHI of 30–55 events/h; however, the pattern of each multiple spike firing were significantly higher in patients with an AHI of >55. These results suggest that sympathetic nerve activity is associated with sleep apnea severity. In addition, single-unit MSNA is a more accurate reflection of sleep apnea severity with alternation of the firing pattern, especially in patients with very severe OSAS. PMID:26973534

  10. Single-Unit Muscle Sympathetic Nerve Activity Reflects Sleep Apnea Severity, Especially in Severe Obstructive Sleep Apnea Patients.

    PubMed

    Hamaoka, Takuto; Murai, Hisayoshi; Kaneko, Shuichi; Usui, Soichiro; Okabe, Yoshitaka; Tokuhisa, Hideki; Kato, Takeshi; Furusho, Hiroshi; Sugiyama, Yu; Nakatsumi, Yasuto; Takata, Shigeo; Takamura, Masayuki

    2016-01-01

    Obstructive sleep apnea syndrome (OSAS) is associated with augmented sympathetic nerve activity, as assessed by multi-unit muscle sympathetic nerve activity (MSNA). However, it is still unclear whether single-unit MSNA is a better reflection of sleep apnea severity according to the apnea-hypopnea index (AHI). One hundred and two OSAS patients underwent full polysomnography and single- and multi-unit MSNA measurements. Univariate and multivariate regression analysis were performed to determine which parameters correlated with OSAS severity, which was defined by the AHI. Single- and multi-unit MSNA were significantly and positively correlated with AHI severity. The AHI was also significantly correlated with multi-unit MSNA burst frequency (r = 0.437, p < 0.0001) and single-unit MSNA spike frequency (r = 0.632, p < 0.0001). Multivariable analysis revealed that SF was correlated most significantly with AHI (T = 7.27, p < 0.0001). The distributions of multiple single-unit spikes per one cardiac interval did not differ between patients with an AHI of <30 and those with and AHI of 30-55 events/h; however, the pattern of each multiple spike firing were significantly higher in patients with an AHI of >55. These results suggest that sympathetic nerve activity is associated with sleep apnea severity. In addition, single-unit MSNA is a more accurate reflection of sleep apnea severity with alternation of the firing pattern, especially in patients with very severe OSAS. PMID:26973534

  11. Effects of sympathetic nerve stimulation on membrane potential, [Ca2+]i and force in the arrested sinus venosus of the toad, Bufo marinus.

    PubMed Central

    Cousins, H M; Bramich, N J

    1997-01-01

    1. The effects of sympathetic nerve stimulation on membrane potential and on the intracellular concentration of calcium ions, [Ca2+]i, were recorded concurrently from the sinus venosus of the toad, Bufo marinus, in preparations where beating had been abolished by adding an organic calcium antagonist to the physiological saline. In a separate set of experiments the effects of sympathetic nerve stimulation on force production were examined. 2. Stimulation of the sympathetic nerves caused a membrane depolarization and a simultaneous increase in [Ca2+]i. Both responses were reduced by dihydroergotamine (20 microM). 3. The membrane depolarization and increase in [Ca2+]i evoked by sympathetic nerve stimulation were abolished by ryanodine (10 microM), or caffeine (3 mM). The effects of caffeine, but not those of ryanodine, were fully reversible. 4. Although the Ca(2+)-ATPase inhibitor thapsigargin (30 microM) itself had little effect on the responses to sympathetic nerve stimulation, in its presence caffeine (3 mM) irreversibly abolished the responses. 5. In the presence of nifedipine (10 microM), sympathetic nerve stimulation caused contractions of the sinus venosus. These responses were abolished by either ryanodine (10 microM) or caffeine (3 mM). 6. The results suggest that neuronally released transmitter activates a complex biochemical pathway which triggers the release of Ca2+ from internal stores. PMID:9423190

  12. 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.

  13. Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans

    NASA Technical Reports Server (NTRS)

    Cui, J.; Wilson, T. E.; Shibasaki, M.; Hodges, N. A.; Crandall, C. G.

    2001-01-01

    To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, 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 < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

  14. 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.

  15. 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.

  16. Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation.

    PubMed

    Cassaglia, Priscila A; Shi, Zhigang; Li, Baoxin; Reis, Wagner L; Clute-Reinig, Nicholas M; Stern, Javier E; Brooks, Virginia L

    2014-04-01

    Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose-anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose-dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch-clamp recordings revealed that both NPY and α-melanocyte-stimulating hormone (α-MSH) inhibit and stimulate, respectively, PVN-RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α-MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy. PMID:24535439

  17. 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. PMID:11356607

  18. Effects of L-carnosine on splenic sympathetic nerve activity and tumor proliferation.

    PubMed

    Horii, Yuko; Shen, Jiao; Fujisaki, Yoshiyuki; Yoshida, Kokichi; Nagai, Katsuya

    2012-02-21

    l-Carnosine (β-alanyl-l-histidine), a dipeptide of the amino acids β-alanine and histidine, is found in mammalian tissues including those in the central nervous system and in skeletal muscles. In the present study, we examined the effects of intraduodenal (ID) injection of l-carnosine on splenic sympathetic nerve activity (splenic-SNA) in urethane-anesthetized rats and found that ID injection of 3.3mg/kg of body weight of l-carnosine significantly suppressed splenic-SNA. Since it has been suggested that splenic-SNA reduction increases natural killer (NK) activity of splenic cells, which in turn elevates tumor immunity, we then investigated the effect of l-carnosine on the proliferation of human colon cancer cells transplanted into athymic nude mice. The findings of this study revealed that 1mg/mL of l-carnosine solution given as the only drinking water inhibited tumor proliferation. These results suggest that l-carnosine suppresses splenic-SNA and inhibits cancer cell proliferation, probably by elevating NK activity. PMID:22240100

  19. Jugular venous overflow of noradrenaline from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans.

    PubMed

    Mitchell, David A; Lambert, Gavin; Secher, Niels H; Raven, Peter B; van Lieshout, Johannes; Esler, Murray D

    2009-06-01

    A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A database was assembled of fifty-six healthy subjects in whom total body noradrenaline spillover (indicative of whole body sympathetic nervous activity), brain noradrenaline spillover and brain lipophlic noradrenaline metabolite (3,4-dihydroxyphenolglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG)) overflow rates were measured. These measurements were also made following ganglion blockade (trimethaphan, n = 6), central sympathetic inhibition (clonidine, n = 4) and neuronal noradrenaline uptake blockade (desipramine, n = 13) and in a group of patients (n = 9) with pure autonomic failure (PAF). The mean brain noradrenline spillover and brain noradrenaline metabolite overflow in healthy subjects were 12.5 +/- 1.8, and 186.4 +/- 25 ng min(-1), respectively, with unilateral jugular venous sampling for both. Total body noradrenaline spillover was 605.8 ng min(-1) +/- 34.4 ng min(-1). As expected, trimethaphan infusion lowered brain noradrenaline spillover (P = 0.03), but perhaps surprisingly increased jugular overflow of brain metabolites (P = 0.01). Suppression of sympathetic nervous outflow with clonidine lowered brain noradrenaline spillover (P = 0.004), without changing brain metabolite overflow (P = 0.3). Neuronal noradrenaline uptake block with desipramine lowered the transcranial plasma extraction of tritiated noradrenaline (P = 0.001). The PAF patients had 77% lower brain noradrenaline spillover than healthy recruits (P = 0.06), indicating that in them sympathetic nerve degeneration extended to the cerebral circulation, but metabolites overflow was similar to healthy subjects (P = 0.3). The invariable discordance between noradrenline spillover and noradrenaline

  20. Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation.

    PubMed

    de Jong, Mark R; Hoogerwaard, Annemiek F; Gal, Pim; Adiyaman, Ahmet; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Ramdat Misier, Anand R; van Hasselt, Boudewijn A A M; Heeg, Jan-Evert; le Polain de Waroux, Jean-Benoit; Lau, Elizabeth O Y; Staessen, Jan A; Persu, Alexandre; Elvan, Arif

    2016-06-01

    Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability.

  1. Tetrahydrobiopterin lowers muscle sympathetic nerve activity and improves augmentation index in patients with chronic kidney disease

    PubMed Central

    Liao, Peizhou; Sher, Salman; Lyles, Robert H.; Deveaux, Don D.; Quyyumi, Arshed A.

    2014-01-01

    Chronic kidney disease (CKD) is characterized by overactivation of the sympathetic nervous system (SNS) that contributes to cardiovascular risk. Decreased nitric oxide (NO) bioavailability is a major factor contributing to SNS overactivity in CKD, since reduced neuronal NO leads to increased central SNS activity. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase that increases NO bioavailability in experimental models of CKD. We conducted a randomized, double-blinded, placebo-controlled trial testing the benefits of oral sapropterin dihydrochloride (6R-BH4, a synthetic form of BH4) in CKD. 36 patients with CKD and hypertension were randomized to 12 wk of 1) 200 mg 6R-BH4 twice daily + 1 mg folic acid once daily; vs. 2) placebo + folic acid. The primary endpoint was a change in resting muscle sympathetic nerve activity (MSNA). Secondary endpoints included arterial stiffness using pulse wave velocity (PWV) and augmentation index (AIx), endothelial function using brachial artery flow-mediated dilation and endothelial progenitor cells, endothelium-independent vasodilatation (EID), microalbuminuria, and blood pressure. We observed a significant reduction in MSNA after 12 wk of 6R-BH4 (−7.5 ± 2.1 bursts/min vs. +3.2 ± 1.3 bursts/min; P = 0.003). We also observed a significant improvement in AIx (by −5.8 ± 2.0% vs. +1.8 ± 1.7 in the placebo group, P = 0.007). EID increased significantly (by +2.0 ± 0.59%; P = 0.004) in the 6R-BH4 group, but there was no change in endothelial function. There was a trend toward a reduction in diastolic blood pressure by −4 ± 3 mmHg at 12 wk with 6R-BH4 (P = 0.055). 6R-BH4 treatment may have beneficial effects on SNS activity and central pulse wave reflections in hypertensive patients with CKD. PMID:25477424

  2. Tetrahydrobiopterin lowers muscle sympathetic nerve activity and improves augmentation index in patients with chronic kidney disease.

    PubMed

    Park, Jeanie; Liao, Peizhou; Sher, Salman; Lyles, Robert H; Deveaux, Don D; Quyyumi, Arshed A

    2015-02-01

    Chronic kidney disease (CKD) is characterized by overactivation of the sympathetic nervous system (SNS) that contributes to cardiovascular risk. Decreased nitric oxide (NO) bioavailability is a major factor contributing to SNS overactivity in CKD, since reduced neuronal NO leads to increased central SNS activity. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase that increases NO bioavailability in experimental models of CKD. We conducted a randomized, double-blinded, placebo-controlled trial testing the benefits of oral sapropterin dihydrochloride (6R-BH4, a synthetic form of BH4) in CKD. 36 patients with CKD and hypertension were randomized to 12 wk of 1) 200 mg 6R-BH4 twice daily + 1 mg folic acid once daily; vs. 2) placebo + folic acid. The primary endpoint was a change in resting muscle sympathetic nerve activity (MSNA). Secondary endpoints included arterial stiffness using pulse wave velocity (PWV) and augmentation index (AIx), endothelial function using brachial artery flow-mediated dilation and endothelial progenitor cells, endothelium-independent vasodilatation (EID), microalbuminuria, and blood pressure. We observed a significant reduction in MSNA after 12 wk of 6R-BH4 (-7.5 ± 2.1 bursts/min vs. +3.2 ± 1.3 bursts/min; P = 0.003). We also observed a significant improvement in AIx (by -5.8 ± 2.0% vs. +1.8 ± 1.7 in the placebo group, P = 0.007). EID increased significantly (by +2.0 ± 0.59%; P = 0.004) in the 6R-BH4 group, but there was no change in endothelial function. There was a trend toward a reduction in diastolic blood pressure by -4 ± 3 mmHg at 12 wk with 6R-BH4 (P = 0.055). 6R-BH4 treatment may have beneficial effects on SNS activity and central pulse wave reflections in hypertensive patients with CKD. PMID:25477424

  3. Mindfulness meditation lowers muscle sympathetic nerve activity and blood pressure in African-American males with chronic kidney disease

    PubMed Central

    Lyles, Robert H.; Bauer-Wu, Susan

    2014-01-01

    Mindfulness meditation (MM) is a stress-reduction technique that may have real biological effects on hemodynamics but has never previously been tested in chronic kidney disease (CKD) patients. In addition, the mechanisms underlying the potential blood pressure (BP)-lowering effects of MM are unknown. We sought to determine whether MM acutely lowers BP in CKD patients, and whether these hemodynamic changes are mediated by a reduction in sympathetic nerve activity. In 15 hypertensive African-American (AA) males with CKD, we conducted a randomized, crossover study in which participants underwent 14 min of MM or 14 min of BP education (control intervention) during two separate random-order study visits. Muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, heart rate (HR), and respiratory rate (RR) were continuously measured at baseline and during each intervention. A subset had a third study visit to undergo controlled breathing (CB) to determine whether a reduction in RR alone was sufficient in exacting hemodynamic changes. We observed a significantly greater reduction in systolic BP, diastolic BP, mean arterial pressure, and HR, as well as a significantly greater reduction in MSNA, during MM compared with the control intervention. Participants had a significantly lower RR during MM; however, in contrast to MM, CB alone did not reduce BP, HR, or MSNA. MM acutely lowers BP and HR in AA males with hypertensive CKD, and these hemodynamic effects may be mediated by a reduction in sympathetic nerve activity. RR is significantly lower during MM, but CB alone without concomitant meditation does not acutely alter hemodynamics or sympathetic activity in CKD. PMID:24829497

  4. Nicotine and sympathetic neurotransmission.

    PubMed

    Haass, M; Kübler, W

    1997-01-01

    Nicotine increases heart rate, myocardial contractility, and blood pressure. These nicotine-induced cardiovascular effects are mainly due to stimulation of sympathetic neurotransmission, as nicotine stimulates catecholamine release by an activation of nicotine acetylcholine receptors localized on peripheral postganglionic sympathetic nerve endings and the adrenal medulla. The nicotinic acetylcholine receptor is a ligand-gated cation channel with a pentameric structure and a central pore with a cation gate, which is essential for ion selectivity and permeability. Binding of nicotine to its extracellular binding site leads to a conformational change of the central pore, which results in the influx of sodium and calcium ions. The resulting depolarization of the sympathetic nerve ending stimulates calcium influx through voltage-dependent N-type calcium channels, which triggers the nicotine-evoked exocytotic catecholamine release. In the isolated perfused guinea-pig heart, cardiac energy depletion sensitizes cardiac sympathetic nerves to the norepinephrine-releasing effect of nicotine, as indicated by a leftward shift of the concentration-response curve, a potentiation of maximum transmitter release, and a delay of the tachyphylaxis of nicotine-evoked catecholamine release. This sensitization was also shown to occur in the human heart under in vitro conditions. Through the intracardiac release of norepinephrine, nicotine induces a beta-adrenoceptor-mediated increase in heart rate and contractility, and an alpha-adrenoceptor-mediated increase in coronary vasomotor tone. The resulting simultaneous increase in oxygen demand and coronary resistance has a detrimental effect on the oxygen balance of the heart, especially in patients with coronary artery disease. Sensitization of the ischemic heart to the norepinephrine-releasing effect of nicotine may be a trigger for acute cardiovascular events in humans, such as acute myocardial infarction and/or life

  5. Influence of age on respiratory modulation of muscle sympathetic nerve activity, blood pressure and baroreflex function in humans

    PubMed Central

    Shantsila, Alena; McIntyre, David B.; Lip, Gregory Y. H.; Fadel, Paul J.; Paton, Julian F. R.; Pickering, Anthony E.

    2015-01-01

    New Findings What is the central question of this study? Does ageing influence the respiratory‐related bursting of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure (Traube–Hering waves) that occur with respiration? What is the main finding and its importance? Despite the age‐related elevation in MSNA, the cyclical inhibition of MSNA during respiration is similar between young and older individuals. Furthermore, central respiratory–sympathetic coupling plays a role in the generation of Traube–Hering waves in both young and older humans. Healthy ageing and alterations in respiratory–sympathetic coupling have been independently linked with heightened sympathetic neural vasoconstrictor activity. We investigated how age influences the respiratory‐related modulation of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure that occur with respiration (Traube–Hering waves; THW). Ten young (22 ± 2 years; mean ± SD) and 10 older healthy men (58 ± 6 years) were studied while resting supine and breathing spontaneously. MSNA, blood pressure and respiration were recorded simultaneously. Resting values were ascertained and respiratory cycle‐triggered averaging of MSNA and blood pressure measurements performed. The MSNA burst incidence was higher in older individuals [22.7 ± 9.2 versus 42.2 ± 13.7 bursts (100 heart beats)−1, P < 0.05], and was reduced to a similar extent in the inspiratory to postinspiratory period in young and older subjects (by ∼25% compared with mid‐ to late expiration). A similar attenuation of MSNA burst frequency (in bursts per minute), amplitude and total activity (burst frequency × mean burst amplitude) was also observed in the inspiratory to postinspiratory period in both groups. A significant positive correlation between respiratory‐related MSNA and the magnitude of

  6. Leptin-receptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic nerve activation in a Caucasian male population.

    PubMed

    Masuo, Kazuko; Straznicky, Nora E; Lambert, Gavin W; Katsuya, Tomohiro; Sugimoto, Ken; Rakugi, Hiromi; Socratous, Florentia; Hastings, Jacqueline; Lambert, Elisabeth A; Ogihara, Toshio; Esler, Murray D

    2008-06-01

    Leptin plays a key role in the regulation of body weight through the sympathetic nervous system; however, the contributions of leptin-receptor polymorphisms to obesity and sympathetic nerve activity have not been fully clarified. In the present study, we examined the relationships between leptin-receptor polymorphisms, plasma leptin and whole-body norepinephrine (NE) spillover as an index of sympathetic nerve activity in a Caucasian male cohort. In 129 young healthy normotensive men with a wide range of body mass index (BMI) (19.4-39.5 kg/m(2)), we measured leptin-receptor polymorphisms (Gln223Arg, Lys656Asn, and Lys109Arg), plasma leptin levels, whole-body NE spillover, whole-body NE clearance, BMI and blood pressure (BP) levels in the supine position after overnight fasting. Overweight-obese (BMI>or=25 kg/m(2)) subjects had significantly greater BMI, BP levels, plasma leptin and whole-body NE spillover compared to lean (BMI<25 kg/m(2)) subjects, but the NE clearance was similar. Overweight-obese subjects had significantly higher frequencies of the Arg223 allele and the Arg223 homozygous allele of Gln223Arg and the Asn656 allele of Lys656Asn compared to lean subjects. Subjects carrying the Arg223 homozygous or the Asn656 allele had higher levels of plasma leptin, BMI, waist circumference, and waist-to-hip ratio, but significantly less whole-body NE spillover, especially when they were also overweight-obese. BP levels and whole-body NE clearance were similar between subjects with and without the Arg223 homozygous or Asn656 allele. No differences were found in the distributions of the Arg109 allele of Lys109Arg polymorphism between nonobese and overweight-obese subjects. In addition, BMI, BP, plasma leptin levels, whole-body NE spillover and whole-body NE clearance were similar between those with and without the Arg109 allele. Together, these findings demonstrate that leptin-receptor polymorphisms were related to the incidence of obesity in a Caucasian male

  7. Cardiopulmonary baroreceptor control of muscle sympathetic nerve activity in heat-stressed humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Etzel, R. A.; Farr, D. B.

    1999-01-01

    Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7-10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 +/- 3 to 39 +/- 3 bursts/min (P < 0. 05). Central blood volume expansion via rapid saline infusion did not significantly decrease MSNA (44 +/- 4 bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 +/- 3 to 93 +/- 4 mmHg (P < 0.05) caused MSNA to decrease from 36 +/- 3 to 15 +/- 4 bursts/min (P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.

  8. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

    PubMed

    Morimoto-Kobayashi, Yumie; Ohara, Kazuaki; Takahashi, Chika; Kitao, Sayoko; Wang, Guanying; Taniguchi, Yoshimasa; Katayama, Mikio; Nagai, Katsuya

    2015-01-01

    Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or

  9. Oral contraceptive use, muscle sympathetic nerve activity, and systemic hemodynamics in young women

    PubMed Central

    Harvey, Ronee E.; Hart, Emma C.; Charkoudian, Nisha; Curry, Timothy B.; Carter, Jason R.; Fu, Qi; Minson, Christopher T.; Joyner, Michael J.; Barnes, Jill N.

    2015-01-01

    Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. While nearly 80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine if women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared to women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (ages 18–35 years old) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53, 25±4 yr) and women with natural menstrual cycles (n=74, 25±4 yr). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure: 89±1 vs. 85±1 mmHg, respectively; p=0.01), although MSNA was similar in both groups (MSNA burst incidence: 16±1 vs. 18±1 bursts/100 heartbeats, respectively, p=0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 vs. 4.7±0.2 L/min, respectively; p=0.47) and total peripheral resistance (19.2±0.8 vs. 20.0±0.9 units, respectively; p=0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use compared to naturally menstruating women in the early follicular phase. PMID:26101348

  10. Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure.

    PubMed

    Abukar, Yonis; May, Clive N; Ramchandra, Rohit

    2016-01-01

    Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg(-1)·h(-1)) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep (n = 6) and sheep with pacing-induced HF (n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (-8 ± 4 mmHg and -4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF.

  11. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity

    PubMed Central

    Morimoto-Kobayashi, Yumie; Ohara, Kazuaki; Takahashi, Chika; Kitao, Sayoko; Wang, Guanying; Taniguchi, Yoshimasa; Katayama, Mikio; Nagai, Katsuya

    2015-01-01

    Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or

  12. Intracarotid hypertonic sodium chloride differentially modulates sympathetic nerve activity to the heart and kidney.

    PubMed

    Frithiof, Robert; Xing, Tao; McKinley, Michael J; May, Clive N; Ramchandra, Rohit

    2014-04-15

    Hypertonic NaCl infused into the carotid arteries increases mean arterial pressure (MAP) and changes sympathetic nerve activity (SNA) via cerebral mechanisms. We hypothesized that elevated sodium levels in the blood supply to the brain would induce differential responses in renal and cardiac SNA via sensors located outside the blood-brain barrier. To investigate this hypothesis, we measured renal and cardiac SNA simultaneously in conscious sheep during intracarotid infusions of NaCl (1.2 M), sorbitol (2.4 M), or urea (2.4 M) at 1 ml/min for 4 min into each carotid. Intracarotid NaCl significantly increased MAP (91 ± 2 to 97 ± 3 mmHg, P < 0.05) without changing heart rate (HR). Intracarotid NaCl was associated with no change in cardiac SNA (11 ± 5.0%), but a significant inhibition of renal SNA (-32.5 ± 6.4%, P < 0.05). Neither intracarotid sorbitol nor urea changed MAP, HR, central venous pressure, cardiac SNA, and renal SNA. The changes in MAP and renal SNA were completely abolished by microinjection of the GABA agonist muscimol (5 mM, 500 nl each side) into the paraventricular nucleus of the hypothalamus (PVN). Infusion of intracarotid NaCl for 20 min stimulated a larger increase in water intake (1,100 ± 75 ml) than intracarotid sorbitol (683 ± 125 ml) or intracarotid urea (0 ml). These results demonstrate that acute increases in blood sodium levels cause a decrease in renal SNA, but no change in cardiac SNA in conscious sheep. These effects are mediated by cerebral sensors located outside the blood-brain barrier that are more responsive to changes in sodium concentration than osmolality. The renal sympathoinhibitory effects of sodium are mediated via a pathway that synapses in the PVN.

  13. Sex comparisons in muscle sympathetic nerve activity and arterial pressure oscillations during progressive central hypovolemia

    PubMed Central

    Carter III, Robert; Hinojosa-Laborde, Carmen; Convertino, Victor A

    2015-01-01

    Increased tolerance to central hypovolemia is generally associated with greater sympathoexcitation, high-frequency oscillatory patterns of mean arterial pressure (MAP), and tachycardia. On average, women are less tolerant to central hypovolemia than men; however, the autonomic mechanisms governing these comparisons are not fully understood. We tested the hypothesis that women with relatively high tolerance (HT) to central hypovolemia would display similar physiological reserve capacity for sympathoexcitation and oscillations in MAP at presyncope compared to HT men. About 10 men and five women were exposed to progressive lower body negative pressure (LBNP) until the presence of presyncopal symptoms. Based on our previous classification system, all subjects were classified as HT because they completed at least −60 mmHg LBNP. Muscle sympathetic serve activity (MSNA) was measured directly from the peroneal nerve via microneurography and arterial pressure (AP) was measured at the finger by photoplethysmography. LBNP time to presyncope was less (P < 0.01) in women (1727 ± 70 sec) than in men (2022 ± 201 sec). At presyncope, average MSNA in men (50 ± 12 bursts/min) and women (51 ± 7 bursts/min) was similar (P = 0.87). Coincident with similar stroke volume (SV) at presyncope, women had similar MAP and heart rates. However, women had less physiological reserve capacity for SV, AP-MSNA coherence, and oscillations in the high-frequency (HF) components of arterial pressure compared to men. Contrary to our hypothesis, lower tolerance to central hypovolemia in women was not associated with sympathoexcitation, but can be explained, in part by lower physiological reserve to elicit oscillatory patterns in AP, maintenance of AP-MSNA coherence and SV when compared to men. PMID:26109186

  14. Sex comparisons in muscle sympathetic nerve activity and arterial pressure oscillations during progressive central hypovolemia.

    PubMed

    Carter, Robert; Hinojosa-Laborde, Carmen; Convertino, Victor A

    2015-06-01

    Increased tolerance to central hypovolemia is generally associated with greater sympathoexcitation, high-frequency oscillatory patterns of mean arterial pressure (MAP), and tachycardia. On average, women are less tolerant to central hypovolemia than men; however, the autonomic mechanisms governing these comparisons are not fully understood. We tested the hypothesis that women with relatively high tolerance (HT) to central hypovolemia would display similar physiological reserve capacity for sympathoexcitation and oscillations in MAP at presyncope compared to HT men. About 10 men and five women were exposed to progressive lower body negative pressure (LBNP) until the presence of presyncopal symptoms. Based on our previous classification system, all subjects were classified as HT because they completed at least -60 mmHg LBNP. Muscle sympathetic serve activity (MSNA) was measured directly from the peroneal nerve via microneurography and arterial pressure (AP) was measured at the finger by photoplethysmography. LBNP time to presyncope was less (P < 0.01) in women (1727 ± 70 sec) than in men (2022 ± 201 sec). At presyncope, average MSNA in men (50 ± 12 bursts/min) and women (51 ± 7 bursts/min) was similar (P = 0.87). Coincident with similar stroke volume (SV) at presyncope, women had similar MAP and heart rates. However, women had less physiological reserve capacity for SV, AP-MSNA coherence, and oscillations in the high-frequency (HF) components of arterial pressure compared to men. Contrary to our hypothesis, lower tolerance to central hypovolemia in women was not associated with sympathoexcitation, but can be explained, in part by lower physiological reserve to elicit oscillatory patterns in AP, maintenance of AP-MSNA coherence and SV when compared to men. PMID:26109186

  15. Oral Contraceptive Use, Muscle Sympathetic Nerve Activity, and Systemic Hemodynamics in Young Women.

    PubMed

    Harvey, Ronee E; Hart, Emma C; Charkoudian, Nisha; Curry, Timothy B; Carter, Jason R; Fu, Qi; Minson, Christopher T; Joyner, Michael J; Barnes, Jill N

    2015-09-01

    Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. Although ≈80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine whether women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared with women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (aged 18-35 years) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53; 25±4 years) and women with natural menstrual cycles (n=74; 25±4 years). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure, 89±1 versus 85±1 mm Hg, respectively; P=0.01), although MSNA was similar in both groups (MSNA burst incidence, 16±1 versus 18±1 bursts/100 heartbeats, respectively; P=0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 versus 4.7±0.2 L/min, respectively; P=0.47) and total peripheral resistance (19.2±0.8 versus 20.0±0.9 U, respectively; P=0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use when compared with naturally menstruating women in the early follicular phase. PMID:26101348

  16. Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure.

    PubMed

    Abukar, Yonis; May, Clive N; Ramchandra, Rohit

    2016-01-01

    Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg(-1)·h(-1)) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep (n = 6) and sheep with pacing-induced HF (n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (-8 ± 4 mmHg and -4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF. PMID:26468257

  17. Low-frequency sinusoidal galvanic stimulation of the left and right vestibular nerves reveals two peaks of modulation in muscle sympathetic nerve activity.

    PubMed

    Hammam, Elie; James, Cheree; Dawood, Tye; Macefield, Vaughan G

    2011-09-01

    Studies previously performed in our laboratory have shown that sinusoidal galvanic vestibular stimulation (sGVS), a means of selectively modulating vestibular input without affecting other inputs, can cause partial entrainment of muscle sympathetic nerve activity (MSNA) at frequencies ranging from 0.2 to 2.0 Hz. Here we test the effect of sGVS on sympathetic outflow when stimulating the vestibular system at lower frequencies. MSNA was recorded via tungsten microelectrodes inserted into the left common peroneal nerve in 12 awake, seated subjects. Bipolar binaural sinusoidal GVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.08, 0.13 and 0.18 Hz. Cross-correlation analysis revealed two bursts of modulation of MSNA for each cycle of stimulation. We believe the primary peak is related to the positive phase of the sinusoid, in which the right vestibular nerve is hyperpolarised and the left vestibular nerve depolarised. Furthermore, we believe the secondary peak is related to the negative phase of the sinusoid (depolarisation of the right vestibular nerve and hyperpolarisation of the left vestibular nerve). This was never observed at higher frequencies of stimulation, presumably because at such frequencies there is insufficient time for a second peak to be expressed. The incidence of double peaks of MSNA was highest at 0.08 Hz and lowest at 0.18 Hz. These observations emphasise the role of the vestibular apparatus in the control of blood pressure, and further suggest convergence of bilateral inputs from vestibular nuclei onto the output nuclei from which MSNA originates, the rostral ventrolateral medulla (RVLM).

  18. Modulation of muscle sympathetic nerve activity by low-frequency physiological activation of the vestibular utricle in awake humans.

    PubMed

    Hammam, Elie; Kwok, Kenny; Macefield, Vaughan G

    2013-09-01

    We recently showed that selective stimulation of one set of otolithic organs-those located in the utricle, sensitive to displacement in the horizontal axis-causes a marked entrainment of skin sympathetic nerve activity (SSNA). Here, we assessed whether muscle sympathetic nerve activity (MSNA) is similarly modulated. MSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in 12 awake subjects, seated (head vertical, eyes closed) on a motorised platform. Slow sinusoidal accelerations-decelerations (±4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at 0.08 Hz. Cross-correlation analysis revealed partial entrainment of MSNA: vestibular modulation was 32 ± 3 % for displacements in the X-axis and 29 ± 3 % in the Y-axis; these were significantly smaller than those evoked in SSNA (97 ± 3 and 91 ± 5 %, respectively). For each sinusoidal cycle, there were two peaks of modulation-one associated with acceleration as the platform moved forward or to the side and one associated with acceleration in the opposite direction. We believe the two peaks reflect inertial displacement of the stereocilia within the utricle during sinusoidal acceleration, which evokes vestibulosympathetic reflexes that are expressed as vestibular modulation of MSNA as well as of SSNA. The smaller vestibular modulation of MSNA can be explained by the dominant modulation of MSNA by the arterial baroreceptors. PMID:23852323

  19. Modulation of muscle sympathetic nerve activity by low-frequency physiological activation of the vestibular utricle in awake humans.

    PubMed

    Hammam, Elie; Kwok, Kenny; Macefield, Vaughan G

    2013-09-01

    We recently showed that selective stimulation of one set of otolithic organs-those located in the utricle, sensitive to displacement in the horizontal axis-causes a marked entrainment of skin sympathetic nerve activity (SSNA). Here, we assessed whether muscle sympathetic nerve activity (MSNA) is similarly modulated. MSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in 12 awake subjects, seated (head vertical, eyes closed) on a motorised platform. Slow sinusoidal accelerations-decelerations (±4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at 0.08 Hz. Cross-correlation analysis revealed partial entrainment of MSNA: vestibular modulation was 32 ± 3 % for displacements in the X-axis and 29 ± 3 % in the Y-axis; these were significantly smaller than those evoked in SSNA (97 ± 3 and 91 ± 5 %, respectively). For each sinusoidal cycle, there were two peaks of modulation-one associated with acceleration as the platform moved forward or to the side and one associated with acceleration in the opposite direction. We believe the two peaks reflect inertial displacement of the stereocilia within the utricle during sinusoidal acceleration, which evokes vestibulosympathetic reflexes that are expressed as vestibular modulation of MSNA as well as of SSNA. The smaller vestibular modulation of MSNA can be explained by the dominant modulation of MSNA by the arterial baroreceptors.

  20. Activation of Medulla-Projecting Perifornical Neurons Modulates the Adrenal Sympathetic Response to Hypoglycemia: Involvement of Orexin Type 2 (OX2-R) Receptors.

    PubMed

    Korim, Willian S; Llewellyn-Smith, Ida J; Verberne, Anthony J M

    2016-02-01

    Iatrogenic hypoglycemia in response to insulin treatment is commonly experienced by patients with type 1 diabetes and can be life threatening. The body releases epinephrine in an attempt to counterregulate hypoglycemia, but the neural mechanisms underlying this phenomenon remain to be elucidated. Orexin neurons in the perifornical hypothalamus (PeH) project to the rostral ventrolateral medulla (RVLM) and are likely to be involved in epinephrine secretion during hypoglycemia. In anesthetized rats, we report that hypoglycemia increases the sympathetic preganglionic discharge to the adrenal gland by activating PeH orexin neurons that project to the RVLM (PeH-RVLM). Electrophysiological characterization shows that the majority of identified PeH-RVLM neurons, including a subpopulation of orexin neurons, are activated in response to hypoglycemia or glucoprivation. Furthermore, the excitatory input from the PeH is mediated by orexin type 2 receptors in the RVLM. These results suggest that activation of orexin PeH-RVLM neurons and orexin type 2 receptors in the RVLM facilitates epinephrine release by increasing sympathetic drive to adrenal chromaffin cells during hypoglycemia.

  1. Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland.

    PubMed

    Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B

    2015-01-01

    Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.

  2. Motion sickness is associated with an increase in vestibular modulation of skin but not muscle sympathetic nerve activity.

    PubMed

    Klingberg, Danielle; Hammam, Elie; Macefield, Vaughan G

    2015-08-01

    We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), delivered bilaterally at frequencies of 0.08-2.00 Hz, causes a pronounced modulation of muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), together with robust frequency-dependent illusions of side-to-side motion. At low frequencies of sGVS (≤0.2 Hz), some subjects report nausea, so we tested the hypothesis that vestibular modulation of MSNA and SSNA is augmented in individuals reporting nausea. MSNA was recorded via tungsten microelectrodes inserted into the left common peroneal nerve in 22 awake, seated subjects; SSNA was recorded in 14 subjects. Bipolar binaural sGVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.08, 0.13, and 0.18 Hz. Nausea was reported by 21 out of 36 subjects (58 %), but across frequencies of sGVS there was no difference in the magnitude of the vestibular modulation of MSNA in subjects who reported nausea (27.1 ± 1.8 %) and those who did not (30.4 ± 2.9 %). This contrasts with the significantly greater vestibular modulation of SSNA with nausea (41.1 ± 2.0 vs. 28.7 ± 3.1 %) and indicates an organ-specific modulation of sympathetic outflow via the vestibular system during motion sickness. PMID:26025612

  3. Vestibular and pulse-related modulation of skin sympathetic nerve activity during sinusoidal galvanic vestibular stimulation in human subjects.

    PubMed

    James, Cheree; Stathis, Alexandra; Macefield, Vaughan G

    2010-04-01

    We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), a means of a selectively modulating vestibular afferent input without affecting other inputs, can cause partial entrainment of muscle sympathetic nerve activity (MSNA). Given that motion sickness causes sweating and pallor, we tested the hypothesis that sGVS also entrains skin sympathetic nerve activity (SSNA), but that the optimal frequencies are closer to those associated with slow postural changes (0.2 Hz). SSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve in 11 awake-seated subjects. Bipolar binaural sinusoidal GVS (+/-2 mA, 200 cycles) was applied to the mastoid processes at frequencies of 0.2, 0.5, 0.8, 1.1, 1.4, 1.7 and 2.0 Hz. All subjects reported strong postural illusions of 'rocking in a boat' or 'swaying in a hammock'. Sinusoidal GVS caused a marked entrainment of SSNA at all frequencies. Measured as the modulation index, vestibular modulation ranged from 81.5 +/- 4.0% at 0.2 Hz to 76.6 +/- 3.6% at 1.7 Hz; it was significantly weaker at 2.0 Hz (63.2 +/- 5.4%). Interestingly, pulse-related modulation of SSNA, which is normally weak, increased significantly during sGVS but was stronger at 0.8 Hz (86.2 +/- 2.0%) than at 0.2 Hz (69.3 +/- 8.3%), the opposite of the pattern seen with vestibular modulation of MSNA. We conclude that vestibular inputs can entrain the firing of cutaneous sympathetic neurones and increase their normally weak pulse-related rhythmicity.

  4. K(ATP)-channel-dependent regulation of catecholaminergic neurons controls BAT sympathetic nerve activity and energy homeostasis.

    PubMed

    Tovar, Sulay; Paeger, Lars; Hess, Simon; Morgan, Donald A; Hausen, A Christine; Brönneke, Hella S; Hampel, Brigitte; Ackermann, P Justus; Evers, Nadine; Büning, Hildegard; Wunderlich, F Thomas; Rahmouni, Kamal; Kloppenburg, Peter; Brüning, Jens C

    2013-09-01

    Brown adipose tissue (BAT) is a critical regulator of glucose, lipid, and energy homeostasis, and its activity is tightly controlled by the sympathetic nervous system. However, the mechanisms underlying CNS-dependent control of BAT sympathetic nerve activity (SNA) are only partly understood. Here, we demonstrate that catecholaminergic neurons in the locus coeruleus (LC) adapt their firing frequency to extracellular glucose concentrations in a K(ATP)-channel-dependent manner. Inhibiting K(ATP)-channel-dependent control of neuronal activity via the expression of a variant K(ATP) channel in tyrosine-hydroxylase-expressing neurons and in neurons of the LC enhances diet-induced obesity in mice. Obesity results from decreased energy expenditure, lower steady-state BAT SNA, and an attenuated ability of centrally applied glucose to activate BAT SNA. This impairs the thermogenic transcriptional program of BAT. Collectively, our data reveal a role of K(ATP)-channel-dependent neuronal excitability in catecholaminergic neurons in maintaining thermogenic BAT sympathetic tone and energy homeostasis.

  5. Diving and exercise: the interaction of trigeminal receptors and muscle metaboreceptors on muscle sympathetic nerve activity in humans.

    PubMed

    Fisher, James P; Fernandes, Igor A; Barbosa, Thales C; Prodel, Eliza; Coote, John H; Nóbrega, Antonio Claudio L; Vianna, Lauro C

    2015-03-01

    Swimming involves muscular activity and submersion, creating a conflict of autonomic reflexes elicited by the trigeminal receptors and skeletal muscle afferents. We sought to determine the autonomic cardiovascular responses to separate and concurrent stimulation of the trigeminal cutaneous receptors and metabolically sensitive skeletal muscle afferents (muscle metaboreflex). In eight healthy men (30 ± 2 yr) muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; Finometer), femoral artery blood flow (duplex Doppler ultrasonography), and femoral vascular conductance (femoral artery blood flow/MAP) were assessed during the following three experimental conditions: 1) facial cooling (trigeminal nerve stimulation), 2) postexercise ischemia (PEI; muscle metaboreflex activation) following isometric handgrip, and 3) trigeminal nerve stimulation with concurrent PEI. Trigeminal nerve stimulation produced significant increases in MSNA total activity (Δ347 ± 167%) and MAP (Δ21 ± 5%) and a reduction in femoral artery vascular conductance (Δ-17 ± 9%). PEI also evoked significant increases in MSNA total activity (Δ234 ± 83%) and MAP (Δ36 ± 4%) and a slight nonsignificant reduction in femoral artery vascular conductance (Δ-9 ± 12%). Trigeminal nerve stimulation with concurrent PEI evoked changes in MSNA total activity (Δ341 ± 96%), MAP (Δ39 ± 4%), and femoral artery vascular conductance (Δ-20 ± 9%) that were similar to those evoked by either separate trigeminal nerve stimulation or separate PEI. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not summate algebraically in eliciting a MSNA and cardiovascular response but rather exhibit synaptic occlusion, suggesting a high degree of convergent inputs on output neurons. PMID:25527781

  6. Diving and exercise: the interaction of trigeminal receptors and muscle metaboreceptors on muscle sympathetic nerve activity in humans.

    PubMed

    Fisher, James P; Fernandes, Igor A; Barbosa, Thales C; Prodel, Eliza; Coote, John H; Nóbrega, Antonio Claudio L; Vianna, Lauro C

    2015-03-01

    Swimming involves muscular activity and submersion, creating a conflict of autonomic reflexes elicited by the trigeminal receptors and skeletal muscle afferents. We sought to determine the autonomic cardiovascular responses to separate and concurrent stimulation of the trigeminal cutaneous receptors and metabolically sensitive skeletal muscle afferents (muscle metaboreflex). In eight healthy men (30 ± 2 yr) muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; Finometer), femoral artery blood flow (duplex Doppler ultrasonography), and femoral vascular conductance (femoral artery blood flow/MAP) were assessed during the following three experimental conditions: 1) facial cooling (trigeminal nerve stimulation), 2) postexercise ischemia (PEI; muscle metaboreflex activation) following isometric handgrip, and 3) trigeminal nerve stimulation with concurrent PEI. Trigeminal nerve stimulation produced significant increases in MSNA total activity (Δ347 ± 167%) and MAP (Δ21 ± 5%) and a reduction in femoral artery vascular conductance (Δ-17 ± 9%). PEI also evoked significant increases in MSNA total activity (Δ234 ± 83%) and MAP (Δ36 ± 4%) and a slight nonsignificant reduction in femoral artery vascular conductance (Δ-9 ± 12%). Trigeminal nerve stimulation with concurrent PEI evoked changes in MSNA total activity (Δ341 ± 96%), MAP (Δ39 ± 4%), and femoral artery vascular conductance (Δ-20 ± 9%) that were similar to those evoked by either separate trigeminal nerve stimulation or separate PEI. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not summate algebraically in eliciting a MSNA and cardiovascular response but rather exhibit synaptic occlusion, suggesting a high degree of convergent inputs on output neurons.

  7. Role of the renal sympathetic nerves in renal sodium/potassium handling and renal damage in spontaneously hypertensive rats

    PubMed Central

    Li, Jianling; He, Qiaoling; Wu, Weifeng; Li, Qingjie; Huang, Rongjie; Pan, Xiaofeng; Lai, Wenying

    2016-01-01

    Renal sympathetic nerve activity has an important role in renal disease-associated hypertension and in the modulation of fluid homeostasis. In the present study, changes in renal function and renal sodium/potassium handling were investigated in groups of 12-week-old male, spontaneously hypertensive rats with renal denervation (RDNX group) or sham denervation (sham group). The RDNX group excreted significantly more sodium than the sham group during the 2-week observation period (P<0.05). Following bilateral renal denervation, the fractional lithium excretion was elevated in the RDNX group compared with the sham group, but no significant effect was observed of renal denervation on the fractional distal reabsorption rate of sodium or the fractional excretion of potassium. Furthermore, the glomerular injury score and the wall-to-lumen ratio of the interlobular artery were significantly lower in the RDNX group than in the sham group (P<0.05). In conclusion, the present study indicates an involvement of the renal sympathetic nerves in the regulation of renal tubular sodium reabsorption in spontaneously hypertensive rats and in the renal damage associated with hypertension. PMID:27698757

  8. Role of the renal sympathetic nerves in renal sodium/potassium handling and renal damage in spontaneously hypertensive rats

    PubMed Central

    Li, Jianling; He, Qiaoling; Wu, Weifeng; Li, Qingjie; Huang, Rongjie; Pan, Xiaofeng; Lai, Wenying

    2016-01-01

    Renal sympathetic nerve activity has an important role in renal disease-associated hypertension and in the modulation of fluid homeostasis. In the present study, changes in renal function and renal sodium/potassium handling were investigated in groups of 12-week-old male, spontaneously hypertensive rats with renal denervation (RDNX group) or sham denervation (sham group). The RDNX group excreted significantly more sodium than the sham group during the 2-week observation period (P<0.05). Following bilateral renal denervation, the fractional lithium excretion was elevated in the RDNX group compared with the sham group, but no significant effect was observed of renal denervation on the fractional distal reabsorption rate of sodium or the fractional excretion of potassium. Furthermore, the glomerular injury score and the wall-to-lumen ratio of the interlobular artery were significantly lower in the RDNX group than in the sham group (P<0.05). In conclusion, the present study indicates an involvement of the renal sympathetic nerves in the regulation of renal tubular sodium reabsorption in spontaneously hypertensive rats and in the renal damage associated with hypertension.

  9. Region-specific changes in sympathetic nerve activity in angiotensin II-salt hypertension in the rat.

    PubMed

    Osborn, John W; Fink, Gregory D

    2010-01-01

    It is now well accepted that many forms of experimental hypertension and human essential hypertension are caused by increased activity of the sympathetic nervous system. However, the role of region-specific changes in sympathetic nerve activity (SNA) in the pathogenesis of hypertension has been difficult to determine because methods for chronic measurement of SNA in conscious animals have not been available. We have recently combined indirect, and continuous and chronic direct, assessment of region-specific SNA to characterize hypertension produced by administration of angiotensin II (Ang II) to rats consuming a high-salt diet (Ang II-salt hypertension). Angiotensin II increases whole-body noradrenaline (NA) spillover and depressor responses to ganglionic blockade in rats consuming a high-salt diet, but not in rats on a normal-salt diet. Despite this evidence for increased 'whole-body SNA' in Ang II-salt hypertensive rats, renal SNA is decreased in this model and renal denervation does not attenuate the steady-state level of arterial pressure. In addition, neither lumbar SNA, which largely targets skeletal muscle, nor hindlimb NA spillover is changed from control levels in Ang II-salt hypertensive rats. However, surgical denervation of the splanchnic vascular bed attenuates/abolishes the increase in arterial pressure and total peripheral resistance, as well as the decrease in vascular capacitance, observed in Ang II-salt hypertensive rats. We hypothesize that the 'sympathetic signature' of Ang II-salt hypertension is characterized by increased splanchnic SNA, no change in skeletal muscle SNA and decreased renal SNA, and this sympathetic signature creates unique haemodynamic changes capable of producing sustained hypertension. PMID:19717492

  10. Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats.

    PubMed

    Molkov, Yaroslav I; Zoccal, Daniel B; Moraes, Davi J A; Paton, Julian F R; Machado, Benedito H; Rybak, Ilya A

    2011-06-01

    Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO(2) evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena, we extended our computational model of the brain stem respiratory network by incorporating a population of presympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments, and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH conditioning increases the CO(2) sensitivity of RTN/pFRG neurons, causing a reduction in both the CO(2) threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparation, we have confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to that in control rats. We conclude that CIH may sensitize central chemoreception and that this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension.

  11. Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings

    PubMed Central

    Silver, Randi B.; Poonwasi, Kumar S.; Seyedi, Nahid; Wilson, Sandy J.; Lovenberg, Timothy W.; Levi, Roberto

    2002-01-01

    Activation of presynatic histamine H3 receptors (H3R) down-regulates norepinephrine exocytosis from cardiac sympathetic nerve terminals, in both normal and ischemic conditions. Analogous to the effects of α2-adrenoceptors, which also act prejunctionally to inhibit norepinephrine release, H3R-mediated antiexocytotic effects could result from a decreased Ca2+ influx into nerve endings. We tested this hypothesis in sympathetic nerve terminals isolated from guinea pig heart (cardiac synaptosomes) and in a model human neuronal cell line (SH-SY5Y), which we stably transfected with human H3R cDNA (SH-SY5Y-H3). We found that reducing Ca2+ influx in response to membrane depolarization by inhibiting N-type Ca2+ channels with ω-conotoxin (ω-CTX) greatly attenuated the exocytosis of [3H]norepinephrine from both SH-SY5Y and SH-SY5Y-H3 cells, as well as the exocytosis of endogenous norepinephrine from cardiac synaptosomes. Similar to ω-CTX, activation of H3R with the selective H3R-agonist imetit also reduced both the rise in intracellular Ca2+ concentration (Cai) and norepinephrine exocytosis in response to membrane depolarization. The selective H3R antagonist thioperamide prevented this effect of imetit. In the parent SH-SY5Y cells lacking H3R, imetit affected neither the rise in Cai nor [3H]norepinephrine exocytosis, demonstrating that the presence of H3R is a prerequisite for a decrease in Cai in response to imetit and that H3R activation modulates norepinephrine exocytosis by limiting the magnitude of the increase in Cai. Inasmuch as excessive norepinephrine exocytosis is a leading cause of cardiac dysfunction and arrhythmias during acute myocardial ischemia, attenuation of norepinephrine release by H3R agonists may offer a novel therapeutic approach to this condition. PMID:11752397

  12. Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents.

    PubMed

    Kanazawa, Hideaki; Ieda, Masaki; Kimura, Kensuke; Arai, Takahide; Kawaguchi-Manabe, Haruko; Matsuhashi, Tomohiro; Endo, Jin; Sano, Motoaki; Kawakami, Takashi; Kimura, Tokuhiro; Monkawa, Toshiaki; Hayashi, Matsuhiko; Iwanami, Akio; Okano, Hideyuki; Okada, Yasunori; Ishibashi-Ueda, Hatsue; Ogawa, Satoshi; Fukuda, Keiichi

    2010-02-01

    Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.

  13. The innervation of the mammalian adrenal gland.

    PubMed Central

    Parker, T L; Kesse, W K; Mohamed, A A; Afework, M

    1993-01-01

    Early conflicting reports and the lack of sensitive anatomical methods have led to an oversimplified view of adrenal gland innervation. It was not until the introduction of nerve fibre tracing techniques in the mid-1970s that the true complexity of adrenal innervation began to emerge. The first part of this article comprises a brief review of these and other relevant reports dealing with both medullary and cortical innervation. In the second part a detailed account is given of the work undertaken in Rex Coupland's Department relating to the innervation of the rodent and primate adrenal medulla using a retrograde fluorescent tracer technique. It was concluded that, in all 3 species studied, the adrenal medulla receives a sympathetic and parasympathetic efferent and an afferent innervation. The possible interrelationship between neural control of cortical and medullar secretions is discussed briefly. Images Fig. 1 Fig. 2 Fig. 5 PMID:8300416

  14. "Real-time" imaging of cortical and subcortical sites of cardiovascular control: concurrent recordings of sympathetic nerve activity and fMRI in awake subjects.

    PubMed

    Macefield, Vaughan G; Henderson, Luke A

    2016-09-01

    We review our approach to functionally identifying cortical and subcortical areas involved in the generation of spontaneous fluctuations in sympathetic outflow to muscle or skin. We record muscle sympathetic nerve activity (MSNA) or skin sympathetic nerve activity (SSNA), via a tungsten microelectrode inserted percutaneously into the common peroneal nerve, at the same time as performing functional magnetic resonance imaging (fMRI) of the brain. By taking advantage of the neurovascular coupling delay associated with BOLD (blood oxygen level dependent) fMRI, and the delay associated with conduction of a burst of sympathetic impulses to the peripheral recording site, we can identify structures in which BOLD signal intensity covaries with MSNA or SSNA. Using this approach, we found MSNA-coupled increases in BOLD signal intensity in the mid-insula and dorsomedial hypothalamus on the left side, and in dorsolateral prefrontal cortex, posterior cingulate cortex, precuneus, ventromedial hypothalamus and rostral ventrolateral medulla on both sides. Conversely, spontaneous bursts of SSNA were positively correlated with BOLD signal intensity in the ventromedial thalamus and posterior insula on the left side, and in the anterior insula, orbitofrontal cortex and frontal cortex on the right side, and in the mid-cingulate cortex and precuneus on both sides. Inverse relationships were observed between MSNA and BOLD signal intensity in the right ventral insula, nucleus tractus solitarius and caudal ventrolateral medulla, and between SSNA and signal intensity in the left orbitofrontal cortex. These results emphasize the contributions of cortical regions of the brain to sympathetic outflow in awake human subjects, and the extensive interactions between cortical and subcortical regions in the ongoing regulation of sympathetic nerve activity to muscle and skin in awake human subjects. PMID:27334958

  15. Longitudinal tracking of muscle sympathetic nerve activity and its relationship with blood pressure in subjects with prehypertension.

    PubMed

    Hering, Dagmara; Kara, Tomas; Kucharska, Wiesława; Somers, Virend K; Narkiewicz, Krzysztof

    2016-06-01

    Prehypertension is associated with increased cardiovascular events. While the "tracking phenomenon" is an important longitudinal characteristic of blood pressure (BP), changes in muscle sympathetic nerve activity (MSNA) over time remain unclear. This study tested the hypothesis that MSNA tracking contributes to BP trends in prehypertension. BP and MSNA were assessed in 13 prehypertensive males at rest, during hand grip and mental stressors at baseline and after 8 years. Baseline office BP averaged 127 ± 2/81 ± 2 mmHg and MSNA 24 ± 4 bursts/min. BP increased by 7 ± 2/5 ± 2 mmHg (P < 0.01) and MSNA by 11 ± 2 bursts/min (P < 0.001) at follow-up. SBP and DBP were interrelated at baseline (r = 0.65, P = 0.02) and at follow-up (r = 0.78, P = 0.002). MSNA tracking (r = 0.82; P < 0.001) was similar to BP. MSNA was strongly related to DBP at baseline (r = 0.73; P < 0.01) and follow-up (r = 0.64; P = 0.01), more so than SBP. BMI increased (P < 0.001) at follow-up but was unrelated to BP or MSNA. Despite comparable pressor and cardiac increases to handgrip and mental stressors, sympathetic responses were blunted, more pronounced to isometric test (P < 0.006) at follow-up. In conclusion, the trend in MSNA corresponds with BP changes over time suggesting that tonic sympathetic activation may contribute to time-related increase in resting BP and the development of sustained hypertension in prehypertension. PMID:26654200

  16. Salivation in the red kangaroo (Macropus rufus) during sympathetic nerve stimulation.

    PubMed

    Beal, A M

    1989-01-01

    1. Continuous electrical stimulation at low frequency (5 Hz) and short pulse duration (500 microseconds) of the cervical sympathetic trunk for periods up to 15 min caused no obvious flow from the parotid or mandibular glands of the red kangaroo. 2. Higher frequencies combined with longer pulse durations caused both glands to secrete. Flow reached maximum in less than 3 min and then declined but, on cessation of stimulation, flow increased again for a short period. This flow response may be caused by the interaction of the secretory response with myoepithelial contraction. 3. The parotid saliva had substantially higher protein, phosphate and hydrogen ion concentrations, and lower sodium concentrations than cholinergic parotid saliva. The low pH indicates bicarbonate concentrations far lower than in other sympathetic salivas. 4. The mandibular saliva had higher protein, urea and potassium, and lower chloride and hydrogen concentrations than cholinergic mandibular saliva.

  17. Salivation in the red kangaroo (Macropus rufus) during sympathetic nerve stimulation.

    PubMed

    Beal, A M

    1989-01-01

    1. Continuous electrical stimulation at low frequency (5 Hz) and short pulse duration (500 microseconds) of the cervical sympathetic trunk for periods up to 15 min caused no obvious flow from the parotid or mandibular glands of the red kangaroo. 2. Higher frequencies combined with longer pulse durations caused both glands to secrete. Flow reached maximum in less than 3 min and then declined but, on cessation of stimulation, flow increased again for a short period. This flow response may be caused by the interaction of the secretory response with myoepithelial contraction. 3. The parotid saliva had substantially higher protein, phosphate and hydrogen ion concentrations, and lower sodium concentrations than cholinergic parotid saliva. The low pH indicates bicarbonate concentrations far lower than in other sympathetic salivas. 4. The mandibular saliva had higher protein, urea and potassium, and lower chloride and hydrogen concentrations than cholinergic mandibular saliva. PMID:2566416

  18. Phrenic and sympathetic nerve responses to glutamergic blockade during normoxia and hypoxia.

    PubMed

    Chae, L O; Melton, J E; Neubauer, J A; Edelman, N H

    1993-04-01

    Because hypoxia increases brain extracellular glutamate levels, we hypothesized that gasping and increased sympathetic activity during severe hypoxia result from glutamergic excitation. To test this hypothesis, we exposed anesthetized paralyzed vagotomized glomectomized cats to hypoxia before and after N-methyl-D-aspartate (NMDA) glutamergic blockade (MK-801, 1 mg/kg iv) or non-NMDA blockade (NBQX, 3 mg/kg iv) while monitoring phrenic neurogram (PN) and inspiratory-synchronous (ISSN) and tonic (TSN) activity in cervical sympathetic neurogram (SN). Before hypoxia, MK-801 caused apneusis and reduced PN and ISSN amplitude by 38 and 84%, respectively, but TSN activity was unaffected. During hypoxia, MK-801 had no effect on PN gasping or TSN activity but reduced ISSN amplitude during gasping. Before hypoxia, NBQX reduced PN and ISSN amplitude by 54 and 60%, respectively but did not affect inspiratory timing or TSN activity. Gasping activity in PN and ISSN and TSN activity during hypoxia were unaffected by NBQX. We conclude that 1) ionotropic glutamergic receptor activation is important for eupneic phrenic patterning but is not involved in genesis of gasping, 2) NMDA receptor activation is involved in integration of respiratory and sympathetic activity, and 3) changes in TSN activity are independent of ionotropic glutamergic receptor activation. PMID:8514717

  19. Acute cyclooxygenase inhibition does not alter muscle sympathetic nerve activity or forearm vasodilator responsiveness in lean and obese adults

    PubMed Central

    Barnes, Jill N.; Charkoudian, Nisha; Matzek, Luke J.; Johnson, Christopher P.; Joyner, Michael J.; Curry, Timothy B.

    2014-01-01

    Abstract Obesity is often characterized by chronic inflammation that may contribute to increased cardiovascular risk via sympathoexcitation and decreased vasodilator responsiveness. We hypothesized that obese individuals would have greater indices of inflammation compared with lean controls, and that cyclooxygenase inhibition using ibuprofen would reduce muscle sympathetic nerve activity (MSNA) and increase forearm blood flow in these subjects. We measured MSNA, inflammatory biomarkers (C‐reactive protein [CRP] and Interleukin‐6 [IL‐6]), and forearm vasodilator responses to brachial artery acetylcholine and sodium nitroprusside in 13 men and women (7 lean; 6 obese) on two separate study days: control (CON) and after 800 mg ibuprofen (IBU). CRP (1.7 ± 0.4 vs. 0.6 ± 0.3 mg/L; P < 0.05) and IL‐6 (4.1 ± 1.5 vs. 1.0 ± 0.1pg/mL; P < 0.05) were higher in the obese group during CON and tended to decrease with IBU (IL‐6: P < 0.05; CRP: P = 0.14). MSNA was not different between groups during CON (26 ± 4 bursts/100 heart beats (lean) versus 26 ± 4 bursts/100 heart beats (obese); P = 0.50) or IBU (25 ± 4 bursts/100 heart beats (lean) versus 30 ± 5 bursts/100 heart beats (obese); P = 0.25), and was not altered by IBU. Forearm vasodilator responses were unaffected by IBU in both groups. In summary, an acute dose of ibuprofen did not alter sympathetic nerve activity or forearm blood flow responses in healthy obese individuals, suggesting that the cyclooxygenase pathway is not a major contributor to these variables in this group. PMID:25347862

  20. Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

    PubMed

    Winston, John H; Sarna, Sushil K

    2016-07-01

    Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats. PMID:27151940

  1. Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients

    PubMed Central

    Groehs, Raphaela V.; Toschi-Dias, Edgar; Antunes-Correa, Ligia M.; Trevizan, Patrícia F.; Rondon, Maria Urbana P. B.; Oliveira, Patrícia; Alves, Maria J. N. N.; Almeida, Dirceu R.; Middlekauff, Holly R.

    2015-01-01

    Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg−1·min−1 were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients. PMID:25747752

  2. Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

    PubMed

    Groehs, Raphaela V; Toschi-Dias, Edgar; Antunes-Correa, Ligia M; Trevizan, Patrícia F; Rondon, Maria Urbana P B; Oliveira, Patrícia; Alves, Maria J N N; Almeida, Dirceu R; Middlekauff, Holly R; Negrão, Carlos E

    2015-05-01

    Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients. PMID:25747752

  3. Macrophage depletion lowers blood pressure and restores sympathetic nerve α2-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats.

    PubMed

    Thang, Loc V; Demel, Stacie L; Crawford, Robert; Kaminski, Norbert E; Swain, Greg M; Van Rooijen, Nico; Galligan, James J

    2015-10-01

    We tested the hypothesis that vascular macrophage infiltration and O2 (-) release impairs sympathetic nerve α2-adrenergic autoreceptor (α2AR) function in mesenteric arteries (MAs) of DOCA-salt hypertensive rats. Male rats were uninephrectomized or sham operated (sham). DOCA pellets were implanted subcutaneously in uninephrectomized rats who were provided high-salt drinking water or high-salt water with apocynin. Sham rats received tap water. Blood pressure was measured using radiotelemetry. Treatment of sham and DOCA-salt rats with liposome-encapsulated clodronate was used to deplete macrophages. After 3-5, 10-13, and 18-21 days of DOCA-salt treatment, MAs and peritoneal fluid were harvested from euthanized rats. Norepinephrine (NE) release from periarterial sympathetic nerves was measured in vitro using amperometry with microelectrodes. Macrophage infiltration into MAs as well as TNF-α and p22(phox) were measured using immunohistochemistry. Peritoneal macrophage activation was measured by flow cytometry. O2 (-) was measured using dihydroethidium staining. Hypertension developed over 28 days, and apocynin reduced blood pressure on days 18-21. O2 (-) and macrophage infiltration were greater in DOCA-salt MAs compared with sham MAs after day 10. Peritoneal macrophage activation occurred after day 10 in DOCA-salt rats. Macrophages expressing TNF-α and p22(phox) were localized near sympathetic nerves. Impaired α2AR function and increased NE release from sympathetic nerves occurred in MAs from DOCA-salt rats after day 18. Macrophage depletion reduced blood pressure and vascular O2 (-) while restoring α2AR function in DOCA-salt rats. Macrophage infiltration into the vascular adventitia contributes to increased blood pressure in DOCA-salt rats by releasing O2 (-), which disrupts α2AR function, causing enhanced NE release from sympathetic nerves.

  4. Coping with chronic social stress in mice: hypothalamic-pituitary-adrenal/ sympathetic-adrenal-medullary axis activity, behavioral changes and effects of antalarmin treatment: implications for the study of stress-related psychopathologies.

    PubMed

    Pérez-Tejada, Joana; Arregi, Amaia; Gómez-Lázaro, Eneritz; Vegas, Oscar; Azpiroz, Arantza; Garmendia, Larraitz

    2013-01-01

    The aim of this study was to analyze the individual differences that lead to the development of psychopathological changes in response to chronic social stress. We also assessed the ability of an antagonist of the corticotrophin-releasing hormone (CRH) receptors to reverse the effects of stress. Male adult mice were exposed to repeated defeat experiences for 21 days using a sensorial contact model. After 18 days of defeat, two groups of subjects were established (active and passive), according to their behaviors during social confrontation. Antalarmin treatment was given for 4 and 6 days. The results corroborated previous data indicating that subjects who adopted a passive coping strategy had higher corticosterone levels after 21 days of defeat and decreased resting levels 3 days later. Moreover, they showed higher resting expression levels of hypothalamic CRH than their active counterparts. On day 24, the experimental animals were subjected to another social defeat to determine whether the stress response remained. The increase in corticosterone and hypothalamic CRH levels was similar for all of the stressed subjects, but the passive subjects also had a greater CRH response in the amygdala. Passive subjects had decreased levels of adrenal dopamine β-hydroxylase, tyrosine hydroxylase and plasma adrenaline compared to the active subjects, and lower plasma noradrenaline levels than manipulated controls. The passive profile of physiological changes in both the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary (SAM) axes has been associated with changes related to mood disorders, such as posttraumatic stress disorder and depression. The active coping profile is characterized by similar corticosterone resting levels to controls and increased SAM activity. Both profiles showed alterations in the novel palatable and forced swimming tests, with the passive profile being the most vulnerable to the effects of stress in this last test. Pharmacological

  5. Sympathetic regulation of estradiol secretion from the ovary.

    PubMed

    Uchida, Sae

    2015-01-01

    It is well known that hormone secretion from endocrine glands is regulated by hierarchical feedback mechanisms. However, although Cannon revealed in the 1920s that sympathoadrenal medullary function increased during emergency situations, no studies on the autonomic nervous regulation of hormone secretion have been undertaken for many years. In the past 40 years, the autonomic nervous regulation of insulin secretion from the pancreas, gastrin secretion from the stomach, glucocorticoid secretion from the adrenal cortex, etc., has been demonstrated. Estradiol secretion from the ovary is strongly controlled by the hypothalamic-pituitary-ovarian axis, and its possible regulation by autonomic nerves has been largely unnoticed. Some histological studies have revealed rich adrenergic sympathetic innervation in the ovary. Recently, it has been demonstrated that the activation of the sympathetic nerves to the ovary directly reduces estradiol secretion from the ovary. This article reviews physiological and morphological studies, primarily in rats, on the sympathetic regulation of estradiol secretion from the ovary.

  6. The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

    PubMed

    Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

    2006-04-01

    Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

  7. Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?

    PubMed

    Crawford, C; Wildman, S S P; Kelly, M C; Kennedy-Lydon, T M; Peppiatt-Wildman, C M

    2013-01-01

    Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important

  8. The role of sympathetic and parasympathetic nerve systems on the smooth muscle of rat seminal vesicles - experimental results and speculation for physiological implication on ejaculation.

    PubMed

    Hsieh, J-T; Kuo, Y-C; Chang, H-C; Liu, S-P; Chen, J-H; Tsai, V F S

    2014-01-01

    Ejaculation is a process involving sympathetic and parasympathetic effects during different stages - emission and ejection. Some conditions of ejaculation dysfunction are associated with autonomic nerves. However, the exact effects of autonomic nerves on ejaculation are not well defined. Autonomic agonists induce different recorded trace patterns of seminal vesicular contraction. The different traces contain different components of phasic and tonic contraction, which may have physiological implications. In this study, we examined isolated rat seminal vesicle (SV) contraction by phenylephrine (PE), acetylcholine, and their respective antagonists and then speculated upon physiological roles of sympathetic and parasympathetic nerves on SV during ejaculation. We found that PE and Ach both achieved good contraction of rat SV. Compared to α1b for sympathetic and M1, M2 for parasympathetic receptors, α1a and M3 are the relatively dominant subtypes on rat SV. Adrenergic and cholinergic agonists cause different trace patterns of SV contraction. We speculated that the sympathetic effect is dominant during emission to squeeze seminal fluid out and that the parasympathetic effect is dominant during ejection to provide an anti-reflux effect on the ejaculatory duct.

  9. Increases in muscle sympathetic nerve activity, heart rate, respiration, and skin blood flow during passive viewing of exercise.

    PubMed

    Brown, Rachael; Kemp, Ursula; Macefield, Vaughan

    2013-01-01

    The cardiovascular and respiratory effects of exercise have been widely studied, as have the autonomic effects of imagined and observed exercise. However, the effects of observed exercise in the first person have not been documented, nor have direct recordings of muscle sympathetic nerve activity (MSNA) been obtained during observed or imagined exercise. The aim of the current study was to measure blood pressure, heart rate, respiration, skin blood flow, sweat release, and MSNA (via microelectrodes inserted into the common peroneal nerve), during observation of exercise from the first person point of view. It was hypothesized that the moving stimuli would produce robust compensatory increases in the above-mentioned parameters as effectively as those generated by mental imagery and-to a lesser extent-actual exercise. Nine subjects watched a first-person running video, allowing them to view the action from the perspective of the runner rather than viewing someone else perform the exercise. On average, statistically significant increases from baseline during the running phase were seen in heart rate, respiratory rate, skin blood flow, and burst amplitude of MSNA. These results suggest that observation of exercise in the first person is a strong enough stimulus to evoke "physiologically appropriate" autonomic responses that have a purely psychogenic origin.

  10. The Role of Hypothalamic mTORC1 Signaling in Insulin Regulation of Food Intake, Body Weight, and Sympathetic Nerve Activity in Male Mice

    PubMed Central

    Muta, Kenjiro; Morgan, Donald A.

    2015-01-01

    Insulin action in the brain particularly the hypothalamus is critically involved in the regulation of several physiological processes, including energy homeostasis and sympathetic nerve activity, but the underlying mechanisms are poorly understood. The mechanistic target of rapamycin complex 1 (mTORC1) is implicated in the control of diverse cellular functions, including sensing nutrients and energy status. Here, we examined the role of hypothalamic mTORC1 in mediating the anorectic, weight-reducing, and sympathetic effects of central insulin action. In a mouse hypothalamic cell line (GT1–7), insulin treatment increased mTORC1 activity in a time-dependent manner. In addition, intracerebroventricular (ICV) administration of insulin to mice activated mTORC1 pathway in the hypothalamic arcuate nucleus, a key site of central action of insulin. Interestingly, inhibition of hypothalamic mTORC1 with rapamycin reversed the food intake- and body weight-lowering effects of ICV insulin. Rapamycin also abolished the ability of ICV insulin to cause lumbar sympathetic nerve activation. In GT1–7 cells, we found that insulin activation of mTORC1 pathway requires phosphatidylinositol 3-kinase (PI3K). Consistent with this, genetic disruption of PI3K in mice abolished insulin stimulation of hypothalamic mTORC1 signaling as well as the lumbar sympathetic nerve activation evoked by insulin. These results demonstrate the importance of mTORC1 pathway in the hypothalamus in mediating the action of insulin to regulate energy homeostasis and sympathetic nerve traffic. Our data also highlight the key role of PI3K as a link between insulin receptor and mTORC1 signaling in the hypothalamus. PMID:25574706

  11. Catheter Ablation of Atrial Fibrillation Raises the Plasma Level of NGF-β Which Is Associated with Sympathetic Nerve Activity

    PubMed Central

    Park, Jae Hyung; Wi, Jin; Lee, Da Lyung; Joung, Boyoung; Lee, Moon Hyoung

    2015-01-01

    Purpose The expression of nerve growth factor-β (NGF-β) is related to cardiac nerve sprouting and sympathetic hyper innervation. We investigated the changes of plasma levels of NGF-β and the relationship to follow-up heart rate variability (HRV) after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Materials and Methods This study included 147 patients with AF (117 men, 55.8±11.5 years, 106 paroxysmal AF) who underwent RFCA. The plasma levels of NGF-β were quantified using double sandwich enzyme linked immunosorbent assay method before (NGF-βpre) and 1 hour after RFCA (NGF-βpost-1hr). HRV at pre-procedure (HRVpre), 3 months (HRVpost-3mo), and 1 year post-procedure (HRVpost-1yr) were analyzed and compared with plasma levels of NGF-β. Results 1) The plasma levels of NGF-β significantly increased after RFCA (20.05±11.09 pg/mL vs. 29.60±19.43 pg/mL, p<0.001). The patients who did not show increased NGF-βpost-1hr were older (p=0.023) and had greater left atrial volume index (p=0.028) than those with increased NGF-βpost-1hr. 2) In patients with NGF-βpre >18 pg/mL, low frequency components (LF)/high-frequency components (HF) (p=0.003) and the number of atrial premature contractions (APCs, p=0.045) in HRVpost-3mo were significantly higher than those with ≤18 pg/mL. 3) The LF/HF at HRVpost-3mo was linearly associated with the NGF-βpre (B=4.240, 95% CI 1.114-7.336, p=0.008) and the NGF-βpost-1hr (B=7.617, 95% CI 2.106-13.127, p=0.007). 4) Both NGF-βpre (OR=1.159, 95% CI 1.045-1.286, p=0.005) and NGF-βpost-1hr (OR=1.098, 95% CI 1.030-1.170, p=0.004) were independent predictors for the increase of LF/HF at HRVpost-3mo. Conclusion AF catheter ablation increases plasma level of NGF-β, and high plasma levels of NGF-βpre was associated with higher sympathetic nerve activity and higher frequency of APCs in HRVpost-3mo. PMID:26446633

  12. Effects of nerve growth factor and heart cell conditioned medium on neurite regeneration of aged sympathetic neurons in culture.

    PubMed

    Uchida, Y; Tomonaga, M

    1985-11-25

    The effects of nerve growth factor (NGF) and heart-cell-conditioned medium (HCM) on the neurite regeneration of aged sympathetic neurons were investigated in culture. Investigation of HCM was carried out by two different methods: one was the use of whole HCM on collagen substratum, which reflected component(s) effective in solution (HCM-S); the other was the use of polyornithine (PORN)-binding component(s) (P-HCM). Superior cervical ganglion neurons prepared from male mice from 6 to 30 months of age were cultured in MEM-10% FCS on collagen or gelatin-PORN substratum for 3 days. The number of neurons with neurites and the length of neurites were quantified as neurite production and elongation, respectively. Neuronal survival was not affected by addition of NGF, HCM-S or P-HCM. Neurite production of early adult neurons was enhanced by NGF, HCM-S or P-HCM. In contrast, neurite production of aged neurons was enhanced by only HCM-S, but not NGF or P-HCM. HCM-S did not promote neurite elongation in neurons at any age. Neurite elongation of early adult neurons was enhanced by NGF or P-HCM. Neurite elongation of aged neurons was enhanced by P-HCM. However, responsiveness of NGF for neurite elongation varied according to substrata. No age-related difference was found in neurite production and elongation in the absence of NGF, HCM-S or P-HCM. These results indicate that responsiveness of aged sympathetic neurons is various in different growth factors.

  13. Usefulness of Cardiac Sympathetic Nerve Imaging Using (123)Iodine-Metaiodobenzylguanidine Scintigraphy for Predicting Sudden Cardiac Death in Patients With Heart Failure.

    PubMed

    Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko

    2016-01-01

    The autonomic nervous system plays an important role in the human heart. Activation of the cardiac sympathetic nervous system is a cardinal pathophysiological abnormality associated with the failing human heart. Myocardial imaging using (123)I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, can be used to investigate the activity of norepinephrine, the predominant neurotransmitter of the sympathetic nervous system. Many clinical trials have demonstrated that (123)I-MIBG scintigraphic parameters predict cardiac adverse events, especially sudden cardiac death, in patients with heart failure. In this review, we summarize results from published studies that have focused on the use of cardiac sympathetic nerve imaging using (123)I-MIBG scintigraphy for risk stratification of sudden cardiac death in patients with heart failure.

  14. Binding, internalization, and retrograde transport of /sup 125/I-nerve growth factor in cultured rat sympathetic neurons

    SciTech Connect

    Claude, P.; Hawrot, E.; Dunis, D.A.; Campenot, R.B.

    1982-01-01

    Sympathetic neurons internalize nerve growth factor (NGF) and transport it retrogradely to their cell bodies where it appears to serve a trophic function in maintaining neuronal survival. We have characterized the binding, internalization, and retrograde transport of /sup 125/I-NGF by cultured rat sympathetic neurons. After 3 to 4 weeks in culture, sympathetic neurons possessed approximately 2 X 10(7) specific, cell surface NGF binding sites per neuron with an apparent affinity constant of 2 to 5 X 10(9) M. The density of binding sites on the plasma membrane of the neurites approximately twice that on the plasma membrane of the cell bodies. Because of the extensive network of neuronal processes, the neurites probably account for more than 99.5% of the total binding in mature cultures. Using electron microscope autoradiography, we localized the distribution of /sup 125/I-NGF in the cell body following a 1-hr exposure to /sup 125/I-NGF. The majority of silver grains were associated with lysosomal organelles, including secondary lysosomes, residual bodies, and multivesicular bodies (MVB). The MVB were the most heavily labeled, with a labeling density (L.D.) of 21, while the lysosomes had a L.D. of 3.1. To study the retrograde transport of /sup 125/I-NGF, neurons were grown in compartmentalized culture dishes and their distal processes were exposed to /sup 125/I-NGF. Radioactive material was transported to the cell bodies at the rate of approximately 3 mm/hr. The transport mechanism was sensitive to colchicine and was saturable with respect to NGF. After 8 hr of transport, when the radioactivity in the cell bodies had reached a steady state, the label again was localized primarily to the MVB (L.D. . 16.8) and the lysosomes (L.D. . 3.8). The nuclei were not labeled significantly and had an overall L.D. of 0.47. We saw no evidence for the accumulation of NGF by the nuclear membrane, the nucleolus, or chromatin.

  15. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    PubMed

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus.

  16. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    PubMed

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus. PMID:26483343

  17. CT-clinical approach to patients with symptoms related to the V, VII, IX-XII cranial nerves and cervical sympathetics

    SciTech Connect

    Kalovidouris, A.; Mancuso, A.A.; Dillon, W.

    1984-06-01

    Forty-three patients who had signs and symptoms possibly related to the extracranial course of cranial nerves V, VII, IX, X-XII, and the cervical sympathetics were examined prospectively using high resolution CT to obtain images of thin sections during rapid drip infusion of contrast material. Anatomic areas in the scan protocols included the posterior fossa, cavernous and paranasal sinuses, skull base, temporal bone, nasopharynx, parotid gland, tongue base, and neck. Nine of the 23 patients with possible fifth nerve deficits had extracranial structural lesions that explained the symptoms; none of these nine, however, had typical trigeminal neuralgia. Of eight patients with peripheral seventh nerve abnormalities, two had positive findings on scans. Of five patients presenting with referred ear pain, three had carcinoma of the upper aerodigestive tract. The authors' experience suggests that patients at high risk for structural lesions responsible for cranial nerve deficits can be selected by clinical criteria. Protocols for each clinical setting are presented.

  18. Vestibular modulation of muscle sympathetic nerve activity by the utricle during sub-perceptual sinusoidal linear acceleration in humans.

    PubMed

    Hammam, Elie; Hau, Chui Luen Vera; Wong, Kwok-Shing; Kwok, Kenny; Macefield, Vaughan G

    2014-04-01

    We assessed the capacity for the vestibular utricle to modulate muscle sympathetic nerve activity (MSNA) during sinusoidal linear acceleration at amplitudes extending from imperceptible to clearly perceptible. Subjects (n = 16) were seated in a sealed room, eliminating visual cues, mounted on a linear motor that could deliver peak sinusoidal accelerations of 30 mG in the antero-posterior direction. Subjects sat on a padded chair with their neck and head supported vertically, thereby minimizing somatosensory cues, facing the direction of motion in the anterior direction. Each block of sinusoidal motion was applied at a time unknown to subjects and in a random order of amplitudes (1.25, 2.5, 5, 10, 20 and 30 mG), at a constant frequency of 0.2 Hz. MSNA was recorded via tungsten microelectrodes inserted into muscle fascicles of the common peroneal nerve. Subjects used a linear potentiometer aligned to the axis of motion to indicate any perceived movement, which was compared with the accelerometer signal of actual room movement. On average, 67% correct detection of movement did not occur until 6.5 mG, with correct knowledge of the direction of movement at ~10 mG. Cross-correlation analysis revealed potent sinusoidal modulation of MSNA even at accelerations subjects could not perceive (1.25-5 mG). The modulation index showed a positive linear increase with acceleration amplitude, such that the modulation was significantly higher (25.3 ± 3.7%) at 30 mG than at 1.25 mG (15.5 ± 1.2%). We conclude that selective activation of the vestibular utricle causes a pronounced modulation of MSNA, even at levels well below perceptual threshold, and provides further evidence in support of the importance of vestibulosympathetic reflexes in human cardiovascular control. PMID:24504198

  19. Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain.

    PubMed

    Chartier, Stephane R; Thompson, Michelle L; Longo, Geraldine; Fealk, Michelle N; Majuta, Lisa A; Mantyh, Patrick W

    2014-11-01

    Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in nonhealed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state.

  20. N-11C-Methyl-Dopamine PET Imaging of Sympathetic Nerve Injury in a Swine Model of Acute Myocardial Ischemia: A Comparison with 13N-Ammonia PET

    PubMed Central

    Zhou, Weina; Wang, Xiangcheng; He, Yulin; Nie, Yongzhen; Zhang, Guojian; Wang, Cheng; Wang, Chunmei; Wang, Xuemei

    2016-01-01

    Objective. Using a swine model of acute myocardial ischemia, we sought to validate N-11C-methyl-dopamine (11C-MDA) as an agent capable of imaging cardiac sympathetic nerve injury. Methods. Acute myocardial ischemia was surgically generated in Chinese minipigs. ECG and serum enzyme levels were used to detect the presence of myocardial ischemia. Paired 11C-MDA PET and 13N-ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after surgery to relate cardiac sympathetic nerve injury to blood perfusion. Results. Seven survived the surgical procedure. The ECG-ST segment was depressed, and levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as the defect volume. Both before and immediately after surgery, the images obtained with 11C-MDA and 13N-ammonia were similar. At 1 to 6 months after surgery, however, 11C-MDA postsurgical left ventricular myocardial defect volume was significantly greater compared to 13N-ammonia. Conclusions. In the Chinese minipig model of acute myocardial ischemia, the extent of the myocardial defect as visualized by 11C-MDA is much greater than would be suggested by blood perfusion images, and the recovery from myocardial sympathetic nerve injury is much slower than the restoration of blood perfusion. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease. PMID:27034950

  1. Impaired increases in skin sympathetic nerve activity contribute to age-related decrements in reflex cutaneous vasoconstriction

    PubMed Central

    Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry; Alexander, Lacy M

    2015-01-01

    Abstract Reflex cutaneous vasoconstriction is impaired in older adults; however, the relative roles of altered skin sympathetic nerve activity (SSNA) and end-organ peripheral vascular responsiveness are unclear. We hypothesized that in older adults whole-body cooling would elicit a blunted SSNA response and cutaneous adrenergic responsiveness would be reduced. Twelve young adults (Y; 24 ± 1 years) and 12 older adults (O; 57 ± 2 years) participated in two protocols. In Protocol 1, SSNA (peroneal microneurography) and red cell flux in the affected dermatome (laser Doppler flowmetry; dorsum of foot) were measured during whole-body cooling (mean skin temperature (Tsk) 30.5°C; water-perfused suit). Mental stress was performed at mean Tsk 34.0°C (thermoneutral) and at 30.5°C. In Protocol 2, an intradermal microdialysis fibre was placed in the skin of the lateral calf for graded infusions of noradrenaline (norepinephrine) (NA; 10−12 to 10−2 m). Cutaneous vascular conductance (CVC = flux/mean arterial pressure) was expressed as a change from baseline (ΔCVCbase). Vasoconstriction was attenuated in O. SSNA increased significantly during cooling in Y (+184 ± 37%; P < 0.05) but not O (+51 ± 12%; P > 0.05). Mental stress at Tsk 30.5°C further increased SSNA in both groups. There was no age-related difference in adrenergic responsiveness to exogenous NA (logEC50: −6.41 ± 0.24 in Y, −6.37 ± 0.25 in O; P > 0.05). While the SSNA response to whole-body cooling is impaired with ageing, SSNA can be further increased by a non-thermoregulatory stimulus. Cutaneous adrenergic sensitivity is not reduced in O. These findings suggest that alterations in afferent signalling or central processing likely contribute to blunted SSNA responses to cooling and subsequent impairments in reflex cutaneous vasoconstriction in ageing. Key points The reduction in skin blood flow during whole-body cooling is impaired in healthy older adults. However, the

  2. Effects of inhaled citronella oil and related compounds on rat body weight and brown adipose tissue sympathetic nerve.

    PubMed

    Batubara, Irmanida; Suparto, Irma H; Sa'diah, Siti; Matsuoka, Ryunosuke; Mitsunaga, Tohru

    2015-03-01

    Citronella oil is one of the most famous Indonesian essential oils, having a distinctive aroma. As with other essential oils, it is crucial to explore the effects of inhalation of this oil. Therefore, the aim of this research was to elucidate the effects of inhalation of citronella oil and its components isolated from Cymbopogon nardus L. (Poaceae), Indonesian local name: "Sereh Wangi" on the body weight, blood lipid profile, and liver function of rats, as well as on the sympathetic nerve activity and temperature of brown adipose tissue. Sprague-Dawley male adult rats fed with high fat diet (HFD) were made to inhale citronella oil, R-(+)-citronellal, and β-citronellol for five weeks, and the observations were compared to those of HFD rats that were not subjected to inhalation treatment. The results showed that inhalation of β-citronellol decreased feed consumption. As a consequence, the percentage of weight gain decreased compared with that in control group and the blood cholesterol level in the β-citronellol group was significantly lowered. Concentration of liver function enzymes were not significantly different among the groups. In conclusion, inhalation of citronella oil, specifically β-citronellol, decreased body weight by decreasing appetite, without any marked changes in liver enzyme concentrations. PMID:25774603

  3. Effects of Inhaled Citronella Oil and Related Compounds on Rat Body Weight and Brown Adipose Tissue Sympathetic Nerve

    PubMed Central

    Batubara, Irmanida; Suparto, Irma H.; Sa’diah, Siti; Matsuoka, Ryunosuke; Mitsunaga, Tohru

    2015-01-01

    Citronella oil is one of the most famous Indonesian essential oils, having a distinctive aroma. As with other essential oils, it is crucial to explore the effects of inhalation of this oil. Therefore, the aim of this research was to elucidate the effects of inhalation of citronella oil and its components isolated from Cymbopogon nardus L. (Poaceae), Indonesian local name: “Sereh Wangi” on the body weight, blood lipid profile, and liver function of rats, as well as on the sympathetic nerve activity and temperature of brown adipose tissue. Sprague-Dawley male adult rats fed with high fat diet (HFD) were made to inhale citronella oil, R-(+)-citronellal, and β-citronellol for five weeks, and the observations were compared to those of HFD rats that were not subjected to inhalation treatment. The results showed that inhalation of β-citronellol decreased feed consumption. As a consequence, the percentage of weight gain decreased compared with that in control group and the blood cholesterol level in the β-citronellol group was significantly lowered. Concentration of liver function enzymes were not significantly different among the groups. In conclusion, inhalation of citronella oil, specifically β-citronellol, decreased body weight by decreasing appetite, without any marked changes in liver enzyme concentrations. PMID:25774603

  4. Effects of inhaled citronella oil and related compounds on rat body weight and brown adipose tissue sympathetic nerve.

    PubMed

    Batubara, Irmanida; Suparto, Irma H; Sa'diah, Siti; Matsuoka, Ryunosuke; Mitsunaga, Tohru

    2015-03-12

    Citronella oil is one of the most famous Indonesian essential oils, having a distinctive aroma. As with other essential oils, it is crucial to explore the effects of inhalation of this oil. Therefore, the aim of this research was to elucidate the effects of inhalation of citronella oil and its components isolated from Cymbopogon nardus L. (Poaceae), Indonesian local name: "Sereh Wangi" on the body weight, blood lipid profile, and liver function of rats, as well as on the sympathetic nerve activity and temperature of brown adipose tissue. Sprague-Dawley male adult rats fed with high fat diet (HFD) were made to inhale citronella oil, R-(+)-citronellal, and β-citronellol for five weeks, and the observations were compared to those of HFD rats that were not subjected to inhalation treatment. The results showed that inhalation of β-citronellol decreased feed consumption. As a consequence, the percentage of weight gain decreased compared with that in control group and the blood cholesterol level in the β-citronellol group was significantly lowered. Concentration of liver function enzymes were not significantly different among the groups. In conclusion, inhalation of citronella oil, specifically β-citronellol, decreased body weight by decreasing appetite, without any marked changes in liver enzyme concentrations.

  5. Effect of exercise-induced activation of sympathetic nerve activity on clearance of 123I-MIBG from the myocardium.

    PubMed

    Sugihara, H; Shiga, K; Terada, K; Kinoshita, N; Taniguchi, Y; Ito, K; Adachi, Y; Ushijima, Y; Nakagawa, M; Maeda, T

    1998-08-01

    The effect of exercise on the cardiac kinetics of 123I-MIBG was investigated in the present study. 123I-MIBG was administered intravenously at rest in 6 healthy male volunteers, and anterior planar and SPECT images were obtained 15 minutes, and 2 and 4 hours after administration (protocol A). After 4 weeks, 123I-MIBG was again administered intravenously at rest, and images were obtained 15 minutes later. After imaging, the subjects ran 10 km in approximately 1 hour, and anterior planar and SPECT images were obtained 2 and 4 hours after administration of 123I-MIBG (protocol B). The heart-to-mediastinum uptake ratio (H/M) was calculated from each anterior planar image, and the mean 123I-MIBG clearance from 15 minutes to 2 hours, and from 2 hours to 4 hours was calculated with a bull's eye display. The H/M was much lower after exercise. The mean clearance rate between 15 minutes and 2 hours in protocol B was significantly higher than that between 2 hours and 4 hours, and that between 15 minutes and 2 hours in protocol A. It was concluded that the clearance rate of 123I-MIBG may be a useful index of cardiac sympathetic nerve activity.

  6. Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis.

    PubMed

    Schneider, Johanna; Lother, Achim; Hein, Lutz; Gilsbach, Ralf

    2011-06-01

    Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine storage. In the medulla, TAC caused an increase in chromaffin cell size but did not result in chromaffin cell proliferation. Ablation of chromaffin α(2C)-adrenoceptors did not affect adrenal weight or epinephrine synthesis. However, unilateral denervation of the adrenal gland completely prevented adrenal hypertrophy and increased catecholamine synthesis. Transcriptome analysis of microdissected adrenal medulla identified 483 up- and 231 downregulated, well-annotated genes after TAC. Among these genes, G protein-coupled receptor kinases 2 (Grk2) and 6 and phenylethanolamine N-methyltransferase (Pnmt) were significantly upregulated by TAC. In vitro, acetylcholine-induced Pnmt and Grk2 expression as well as enhanced epinephrine content was prevented by inhibition of nicotinic acetylcholine receptors and Ca(2+)/calmodulin-dependent signaling. Thus, activation of preganglionic sympathetic nerves innervating the adrenal medulla plays an essential role in inducing adrenal hypertrophy, enhanced catecholamine synthesis and induction of Grk2 expression after cardiac pressure overload.

  7. 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. PMID:21984731

  8. Stimulation of the sympathetic perimesenteric arterial nerves releases neuropeptide Y potentiating the vasomotor activity of noradrenaline: involvement of neuropeptide Y-Y1 receptors.

    PubMed

    Donoso, M V; Brown, N; Carrasco, C; Cortes, V; Fournier, A; Huidobro-Toro, J P

    1997-09-01

    Neuropeptide Y (NPY) appears to be involved in the sympathetic regulation of vascular tone. To assess the putative role of NPY in mesenteric circulation, the release and biological effect of NPY were examined after electrical stimulation of perimesenteric arterial nerves. Nerve stimulation with trains of 2-30 Hz increased the perfusion pressure of the arterially perfused rat mesenteric bed in a frequency- and time-dependent fashion. Trains of 15-30 Hz significantly displaced to the left, approximately threefold, the noradrenaline (NA)-induced pressor concentration-response curve, in addition to increasing significantly its efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical stimulation effect, causing a threefold leftward shift of the NA concentration-response curve and increasing the maximal NA response. These effects were antagonized by 100 nM BIBP 3226, indicating the activity of NPY-Y1 receptors. Electrical stimulation of the perimesenteric nerves released immunoreactive NPY (ir-NPY) in a frequency-dependent fashion; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC. Both the electrically induced pressor response and the calcium-dependent release of NPY were obliterated in preparations perfused with 1 microM guanethidine or in rats pretreated intravenously for 48 h with 6-hydroxydopamine, thus revealing the sympathetic origin of these phenomena. Only a small proportion of the total NPY content in the perimesenteric arterial nerves is released after electrical stimulation. Chromatographic studies of the physiological sources of the ir-NPY support that NPY fragments are generated via peptidase degradation. The present findings demonstrate that NPY is released from the perimesenteric arterial sympathetic nerves and acts, via the activation of NPY-Y1 receptors, as the mediator responsible for the potentiation of NA's effect on perfusion pressure in the isolated rat mesenteric bed.

  9. Some properties of the presynaptic nerve terminals in a mammalian sympathetic ganglion

    PubMed Central

    Dunant, Y.

    1972-01-01

    1. Superior cervical ganglia of adult rats were excised and maintained in vitro in stable conditions. Potentials were recorded with external electrodes. After transmission was blocked by mecamylamine, a small potential change was recorded from the rostral area of the ganglion in response to preganglionic stimulation. 2. This electrical response was identified as the presynaptic action potential recorded from the nerve terminals by a number of criteria based on histological and physiological considerations including the disappearance of the spike in a glucose free solution. As shown by Nicolescu, Dolivo, Rouiller & Foroglou-Kerameus (1966) on the same preparation this condition causes an irreversible and selective lesion of the presynaptic nerve endings. 3. A suitable concentration of mecamylamine permitted the presynaptic response and the excitatory post-synaptic potential (EPSP) to be recorded simultaneously. As the stimulus was increased, the EPSP increased linearly with the amplitude of the presynaptic response. 4. After replacement of potassium ions in the bathing solution by caesium and during the early phase of post-tetanic facilitation there was an increase in the presynaptic response accompanied by a disproportionate increase in the EPSP. 5. No changes in the presynaptic response were found in the presence of the following drugs, all of which depressed the EPSP: acetylcholine, hemicholinium, curare, further doses of ganglion-blocking agents, and high Mg2+ and low Ca2+ concentrations. 6. Ouabain (4·5 × 10-4 M) reversibly decreased the amplitude of the presynaptic response and increased the spontaneous release of transmitter. The EPSP was at first enhanced and then depressed. PMID:4335802

  10. A microcontroller-based telemetry system for sympathetic nerve activity and ECG measurement.

    PubMed

    Harada, E; Yonezawa, Y; Caldwell, W M; Hahn, A W

    1999-01-01

    A telemetry system employing a low power 8-bit microcontroller has been developed for chronic unanesthetized small animal studies. The two-channel system is designed for use with animals in shielded cages. Analog signals from implantable ECG and nerve electrodes are converted to an 8-bit serial digital format. This is accomplished by individual 8 bit A/D converters included in the microcontroller, which also has serial I/O port. The converted serial binary code is applied directly to an antenna wire. Therefore, the system does not need to employ a separate transmitter, such as in FM or infrared optical telemeters. The system is used in a shielded animal cage to reduce interference from external radio signals and 60 Hz power line fields. The code is received by a high input impedance amplifier in the cage and is then demodulated. The telemeter is powered by a small 3 V lithium battery, which provides 100 hours of continuous operation. The circuit is constructed on two 25 x 25 mm. printed circuit boards and encapsulated in epoxy, yielding a total volume of 6.25 cc. The weight is 15 g. PMID:11143393

  11. Central correlation of muscle sympathetic nerve activation during baroreflex unloading - a microneurography-positron emission tomography study.

    PubMed

    Krämer, Heidrun H; Ament, Stephan-Johann; Breimhorst, Markus; Klega, Andre; Schmieg, Katharina; Endres, Corina; Buchholz, Hans-Georg; Elam, Mikael; Schreckenberger, Mathias; Birklein, Frank

    2014-02-01

    The baroreceptor reflex controls spontaneous fluctuations in blood pressure. One major control variable of the baroreflex is the sympathetic vasoconstrictor activity to muscles [MSNA; burst frequency (BF) and burst incidence (BI)], which can be quantitatively assessed by microneurography. We aimed to investigate the central regions involved in baroreflex regulation of MSNA. Healthy men (mean age 25 years) participated in three experimental sessions. (i) Microneurography recordings of MSNA from the left peroneal nerve during rest and baroreflex unloading, induced by lower body negative pressure (LBNP; -40 mmHg). If MSNA could be reliably recorded throughout this procedure (n = 15), the subjects entered the positron emission tomography (PET) experiments. The two PET sessions took place in a randomised order. Cerebral glucose metabolism (18-fluorodeoxyglucose) was analysed after: (ii) baroreflex unloading (LBNP); and (iii) control condition (lying in the LBNP chamber without suction). The PET data were analysed employing SPM8. LBNP elicited a significant increase in MSNA in all successfully recorded subjects (BI: P = 0.001; F = 5.54; BF: P < 0.001; F = 36.59). As compared with the control condition, LBNP was associated with increased PET regional glucose metabolism bilaterally in the orbitofrontal cortex (OFC; BA 11, 47). Related to the rise of BF, there was increased activation of the left OFC (BA 11); related to the rise of BI there was increased activation of the brainstem corresponding to the rostral ventrolateral medulla. Our data support a role for the ventrolateral medulla and the OFC in baroreflex-mediated control of MSNA in humans. PMID:24528135

  12. Circumferential targeted renal sympathetic nerve denervation with preservation of the renal arterial wall using intra-luminal ultrasound

    NASA Astrophysics Data System (ADS)

    Roth, Austin; Coleman, Leslie; Sakakura, Kenichi; Ladich, Elena; Virmani, Renu

    2015-03-01

    An intra-luminal ultrasound catheter system (ReCor Medical's Paradise System) has been developed to provide circumferential denervation of the renal sympathetic nerves, while preserving the renal arterial intimal and medial layers, in order to treat hypertension. The Paradise System features a cylindrical non-focused ultrasound transducer centered within a balloon that circulates cooling fluid and that outputs a uniform circumferential energy pattern designed to ablate tissues located 1-6 mm from the arterial wall and protect tissues within 1 mm. RF power and cooling flow rate are controlled by the Paradise Generator which can energize transducers in the 8.5-9.5 MHz frequency range. Computer simulations and tissue-mimicking phantom models were used to develop the proper power, cooling flow rate and sonication duration settings to provide consistent tissue ablation for renal arteries ranging from 5-8 mm in diameter. The modulation of these three parameters allows for control over the near-field (border of lesion closest to arterial wall) and far-field (border of lesion farthest from arterial wall, consisting of the adventitial and peri-adventitial spaces) depths of the tissue lesion formed by the absorption of ultrasonic energy and conduction of heat. Porcine studies have confirmed the safety (protected intimal and medial layers) and effectiveness (ablation of 1-6 mm region) of the system and provided near-field and far-field depth data to correlate with bench and computer simulation models. The safety and effectiveness of the Paradise System, developed through computer model, bench and in vivo studies, has been demonstrated in human clinical studies.

  13. Changes in muscle sympathetic nerve activity and vascular responses evoked in the spinotrapezius muscle of the rat by systemic hypoxia

    PubMed Central

    Hudson, Steven; Johnson, Christopher D; Marshall, Janice M

    2011-01-01

    Abstract Responses evoked in muscle sympathetic nerve activity (MSNA) by systemic hypoxia have received relatively little attention. Moreover, MSNA is generally identified from firing characteristics in fibres supplying whole limbs: their actual destination is not determined. We aimed to address these limitations by using a novel preparation of spinotrapezius muscle in anaesthetised rats. By using focal recording electrodes, multi-unit and discriminated single unit activity were recorded from the surface of arterial vessels. This had cardiac- and respiratory-related activities expected of MSNA, and was increased by baroreceptor unloading, decreased by baroreceptor stimulation and abolished by autonomic ganglion blockade. Progressive, graded hypoxia (breathing sequentially 12, 10, 8% O2 for 2 min each) evoked graded increases in MSNA. In single units, mean firing frequency increased from 0.2 ± 0.04 in 21% O2 to 0.62 ± 0.14 Hz in 8% O2, while instantaneous frequencies ranged from 0.04–6 Hz in 21% O2 to 0.09–20 Hz in 8% O2. Concomitantly, arterial pressure (ABP), fell and heart rate (HR) and respiratory frequency (RF) increased progressively, while spinotrapezius vascular resistance (SVR) decreased (Spinotrapezius blood flow/ABP), indicating muscle vasodilatation. During 8% O2 for 10 min, the falls in ABP and SVR were maintained, but RF, HR and MSNA waned towards baselines from the second to the tenth minute. Thus, we directly show that MSNA increases during systemic hypoxia to an extent that is mainly determined by the increases in peripheral chemoreceptor stimulation and respiratory drive, but its vasoconstrictor effects on muscle vasculature are largely blunted by local dilator influences, despite high instantaneous frequencies in single fibres. PMID:21486771

  14. Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

    PubMed

    Pinkham, Maximilian I; Whalley, Gillian A; Guild, Sarah-Jane; Malpas, Simon C; Barrett, Carolyn J

    2015-07-15

    There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 ± 6 vs. 84 ± 5% in male sham group) and OVX large MI group (37 ± 3 vs. 75 ± 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI. PMID:25994953

  15. Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

    PubMed

    Pinkham, Maximilian I; Whalley, Gillian A; Guild, Sarah-Jane; Malpas, Simon C; Barrett, Carolyn J

    2015-07-15

    There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 ± 6 vs. 84 ± 5% in male sham group) and OVX large MI group (37 ± 3 vs. 75 ± 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI.

  16. 4-[18F]fluoro-m-hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography

    PubMed Central

    Jang, Keun Sam; Jung, Yong-Woon; Gu, Guie; Koeppe, Robert A.; Sherman, Phillip S.; Quesada, Carole A.; Raffel, David M.

    2013-01-01

    4-[18F]fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG, [18F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [18F]1 was developed in which the intermediate 4-[18F]fluoro-m-tyramine ([18F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [18F]fluorination. In PET imaging studies in rhesus macaque monkeys, [18F]1 demonstrated high quality cardiac images with low uptake in lungs and liver. Compartmental modeling of [18F]1 kinetics provided ‘net uptake rate’ constants Ki (mL/min/g wet) and Patlak graphical analysis of [18F]1 kinetics provided Patlak slopes Kp (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [18F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET. PMID:23965035

  17. Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

    PubMed Central

    Chartier, Stephane R.; Thompson, Michelle L.; Longo, Geraldine; Fealk, Michelle N.; Majuta, Lisa A.; Mantyh, Patrick W.

    2014-01-01

    Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in non-healed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+ days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state. PMID:25196264

  18. Renal glucose release during hypoglycemia is partly controlled by sympathetic nerves – a study in pigs with unilateral surgically denervated kidneys

    PubMed Central

    Bischoff, Sabine J; Schmidt, Martin; Lehmann, Thomas; Schwab, Matthias; Matziolis, Georg; Saemann, Alexander; Schiffner, René

    2015-01-01

    Catecholamines are known to increase renal glucose release during hypoglycemia. The specific extent of the contribution of different sources of catecholamines, endocrine delivery via circulation or release from autonomous sympathetic renal nerves, though, is unknown. We tested the hypothesis that sympathetic renal innervation plays a major role in the regulation of renal gluconeogenesis. For this purpose, instrumented adolescent pigs had one kidney surgically denervated while the other kidney served as a control. A hypoglycemic clamp with arterial blood glucose below 2 mmol/L was maintained for 75 min. Arteriovenous blood glucose difference, inulin clearance, p-aminohippurate clearance, and sodium excretion were measured in intervals of 15 min separately for both kidneys. Blood glucose was lowered to 0.84 ± 0.33 mmol/L for 75 min. The side-dependent renal net glucose release (SGN) decreased significantly after the unilateral ablation of renal nerves. In the linear mixed model, renal denervation had a significant inhibitory effect on renal net glucose release (P = 0.036). The SGN of the ablated kidney decreased by 0.02 mmol/min and was equivalent to 43.3 ± 23.2% of the control (nonablated) kidney in the pigs. This allows the conclusion that renal glucose release is partly controlled by sympathetic nerves. This may be relevant in humans as well, and could explain the increased risk of severe hypoglycemia of patients with diabetes mellitus and autonomous neuropathy. The effects of denervation on renal glucose metabolism should be critically taken into account when considering renal denervation as a therapy in diabetic patients. PMID:26564063

  19. Subcutaneous nerve activity is more accurate than the heart rate variability in estimating cardiac sympathetic tone in ambulatory dogs with myocardial infarction

    PubMed Central

    Chan, Yi-Hsin; Tsai, Wei-Chung; Shen, Changyu; Han, Seongwook; Chen, Lan S.; Lin, Shien-Fong; Chen, Peng-Sheng

    2015-01-01

    Background We recently reported that subcutaneous nerve activity (SCNA) can be used to estimate sympathetic tone. Objectives To test the hypothesis that left thoracic SCNA is more accurate than heart rate variability (HRV) in estimating cardiac sympathetic tone in ambulatory dogs with myocardial infarction (MI). Methods We used an implanted radiotransmitter to study left stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and thoracic SCNA in 9 dogs at baseline and up to 8 weeks after MI. HRV was determined based by time-domain, frequency-domain and non-linear analyses. Results The correlation coefficients between integrated SGNA and SCNA averaged 0.74 (95% confidence interval (CI), 0.41–1.06) at baseline and 0.82 (95% CI, 0.63–1.01) after MI (P<.05 for both). The absolute values of the correlation coefficients were significant larger than that between SGNA and HRV analysis based on time-domain, frequency-domain and non-linear analyses, respectively, at baseline (P<.05 for all) and after MI (P<.05 for all). There was a clear increment of SGNA and SCNA at 2, 4, 6 and 8 weeks after MI, while HRV parameters showed no significant changes. Significant circadian variations were noted in SCNA, SGNA and all HRV parameters at baseline and after MI, respectively. Atrial tachycardia (AT) episodes were invariably preceded by the SCNA and SGNA, which were progressively increased from 120th, 90th, 60th to 30th s before the AT onset. No such changes of HRV parameters were observed before AT onset. Conclusion SCNA is more accurate than HRV in estimating cardiac sympathetic tone in ambulatory dogs with MI. PMID:25778433

  20. Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats

    PubMed Central

    Maranon, Rodrigo; Lima, Roberta; Spradley, Frank T.; do Carmo, Jussara M.; Zhang, Howei; Smith, Andrew D.; Bui, Elizabeth; Thomas, R. Lucas; Moulana, Mohadetheh; Hall, John E.; Granger, Joey P.

    2015-01-01

    Women with polycystic ovary syndrome (PCOS) have hyperandrogenemia and increased prevalence of risk factors for cardiovascular disease, including elevated blood pressure. We recently characterized a hyperandrogenemic female rat (HAF) model of PCOS [chronic dihydrotestosterone (DHT) beginning at 4 wk of age] that exhibits similar characteristics as women with PCOS. In the present studies we tested the hypotheses that the elevated blood pressure in HAF rats is mediated in part by sympathetic activation, renal nerves, and melanocortin-4 receptor (MC4R) activation. Adrenergic blockade with terazosin and propranolol or renal denervation reduced mean arterial pressure (MAP by telemetry) in HAF rats but not controls. Hypothalamic MC4R expression was higher in HAF rats than controls, and central nervous system MC4R antagonism with SHU-9119 (1 nmol/h icv) reduced MAP in HAF rats. Taking a genetic approach, MC4R null and wild-type (WT) female rats were treated with DHT or placebo from 5 to 16 wk of age. MC4R null rats were obese and had higher MAP than WT control rats, and while DHT increased MAP in WT controls, DHT failed to further increase MAP in MC4R null rats. These data suggest that increases in MAP with chronic hyperandrogenemia in female rats are due, in part, to activation of the sympathetic nervous system, renal nerves, and MC4R and may provide novel insights into the mechanisms responsible for hypertension in women with hyperandrogenemia such as PCOS. PMID:25695289

  1. Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.

    PubMed

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2014-02-01

    Previously we have shown that stimulation of inhibitory A1 adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A2a adenosine receptors, which dominate over A1 receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 receptors differentially inhibiting regional sympathetic CCR responses (adrenal>lumbar>renal). In urethane/chloralose anesthetized rats (n=38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (1-8μg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20pmol/50nl, ZM-241385 40pmol/100nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A2a receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension. PMID:24216055

  2. Leptin acts in the forebrain to differentially influence baroreflex control of lumbar, renal, and splanchnic sympathetic nerve activity and heart rate.

    PubMed

    Li, Baoxin; Shi, Zhigang; Cassaglia, Priscila A; Brooks, Virginia L

    2013-04-01

    Although leptin is known to increase sympathetic nerve activity (SNA), we tested the hypothesis that leptin also enhances baroreflex control of SNA and heart rate (HR). Using α-chloralose anesthetized male rats, mean arterial pressure (MAP), HR, lumbar SNA (LSNA), splanchnic SNA (SSNA), and renal SNA (RSNA) were recorded before and for 2 hours after lateral cerebroventricular leptin or artificial cerebrospinal fluid administration. Baroreflex function was assessed using a 4-parameter sigmoidal fit of HR and SNA responses to slow ramp (3-5 minutes) changes in MAP, induced by intravenous infusion of nitroprusside and phenylephrine. Leptin (3 μg) increased (P<0.05) basal LSNA, SSNA, RSNA, HR, and MAP, and the LSNA, SSNA, RSNA, and HR baroreflex maxima. Leptin also increased gain of baroreflex control of LSNA and RSNA, but not of SSNA or HR. The elevations in HR were eliminated by pretreatment with methscopalamine, to block parasympathetic nerve activity; however, after cardiac sympathetic blockade with atenolol, leptin still increased basal HR and MAP and the HR baroreflex maximum and minimum. Leptin (1.5 μg) also increased LSNA and enhanced LSNA baroreflex gain and maximum, but did not alter MAP, HR, or the HR baroreflex. Lateral cerebroventricular artificial cerebrospinal fluid had no effects. Finally, to test whether leptin acts in the brain stem, leptin (3 μg) was infused into the 4th ventricle; however, no significant changes were observed. In conclusion, leptin acts in the forebrain to differentially influence baroreflex control of LSNA, RSNA, SSNA, and HR, with the latter action mediated via suppression of parasympathetic nerve activity. PMID:23424232

  3. Sympathetic nervous system and spaceflight

    NASA Astrophysics Data System (ADS)

    Cooke, William H.; Convertino, Victor A.

    2007-02-01

    Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity. Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability. Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance. Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.

  4. Nerve Growth Factor is Required for Induction of c-Fos Immunoreactivity by Serum, Depolarization, Cyclic AMP or Trauma in Cultured Rat Sympathetic Neurons.

    PubMed

    Buckmaster, A; Nobes, C D; Edwards, S N; Tolkovsky, A M

    1991-01-01

    Nerve growth factor (NGF) induces transient Fos-immunoreactivity (Fos-IR) independently of any other factor, both in newly isolated rat sympathetic neurons and in established cultures after NGF deprivation. The same proportion of neurons that express Fos-IR in response to NGF also survive. In addition to direct stimulation of Fos-IR expression, the presence or recent exposure to NGF is required to obtain Fos-IR expression by other stimuli. In newly isolated neurons no Fos-IR is detected in response to stimulation by serum alone and a response to depolarization or cyclic AMP is obtained only if neurons are stimulated within a short period after ganglion excision. In established cultures none of these stimuli, nor the trauma of cutting neurites or spiking cell bodies with a microinjection needle induce Fos-IR unless NGF is present or had been removed for <8 - 16 h. The lack of response is not due to a general decrease in the rate of protein or RNA synthesis. These findings show that in regenerating sympathetic neurons NGF induces c-Fos and suggest that NGF may activate a master trigger that is required for c-Fos expression to be induced by other stimuli.

  5. [Correlations between the coefficient of variation of RR intervals and sympathetic nerve activity following superior tilting in normotensive subjects and in patients with essential hypertension].

    PubMed

    Shimazaki, M; Kikuchi, K; Yamaji, I; Kobayakawa, H; Yamamoto, M; Kudo, C; Wada, A; Mukai, H; Iimura, O

    1991-01-01

    The relationship between changes in sympathetic nerve activity and those in parasympathetic tone with a change in position was investigated in patients with essential hypertension using the coefficient of variation of RR intervals on electrocardiograms (CVRR). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA) and CVRR were measured in a supine position at rest and 20 min after having the head tilted 60 degrees superiorly in 10 normotensives (NT: 51.9 +/- 3.0 yrs) and 7 essential hypertensive patients (EHT: 51.0 +/- 2.8 yrs). After changing the position, CVRR decreased significantly in the NT, but not in the EHT; whereas, significant increases of both HR and pNA without significant changes in MAP were shown in both groups. A significant negative correlation between percentage changes in CVRR (% delta CVRR) and pNA (% delta pNA) were observed in the NT, but not in the EHT. However, there was no relationship of % delta CVRR to % delta MAP or to % delta HR in either group. It was suggested from the changes in CVRR that suppression of the parasympathetic tone, which occurs in the NT group corresponding to sympathetic augmentation to present a decrease in blood pressure with a change in position, may be impaired in the EHT group.

  6. Inter-Individual Responses to Experimental Muscle Pain: Baseline Physiological Parameters Do Not Determine Whether Muscle Sympathetic Nerve Activity Increases or Decreases During Pain

    PubMed Central

    Kobuch, Sophie; Fazalbhoy, Azharuddin; Brown, Rachael; Macefield, Vaughan G.

    2015-01-01

    We have previously reported that there are inter-individual differences in the cardiovascular responses to experimental muscle pain, which are consistent over time: intramuscular infusion of hypertonic saline, causing pain lasting ~60 min, increases muscle sympathetic nerve activity (MSNA)—as well as blood pressure and heart rate—in certain subjects, but decrease it in others. Here, we tested the hypothesis that baseline physiological parameters (resting MSNA, heart rate, blood pressure, heart rate variability) determine the cardiovascular responses to long-lasting muscle pain. MSNA was recorded from the common peroneal nerve, together with heart rate and blood pressure, during a 45-min intramuscular infusion of hypertonic saline solution into the tibialis anterior of 50 awake human subjects (25 females and 25 males). Twenty-four subjects showed a sustained increase in mean amplitude of MSNA (160.9 ± 7.3%), while 26 showed a sustained decrease (55.1 ± 3.5%). Between the increasing and decreasing groups there were no differences in baseline MSNA (19.0 ± 1.5 vs. 18.9 ± 1.2 bursts/min), mean BP (88.1 ± 5.2 vs. 88.0 ± 3.8 mmHg), HR (74.7 ± 2.0 vs. 72.8 ± 1.8 beats/min) or heart rate variability (LF/HF 1.8 ± 0.2 vs. 2.2 ± 0.3). Furthermore, neither sex nor body mass index had any effect on whether MSNA increased or decreased during tonic muscle pain. We conclude that the measured baseline physiological parameters cannot account for the divergent sympathetic responses during tonic muscle pain. PMID:26733786

  7. Inter-Individual Responses to Experimental Muscle Pain: Baseline Physiological Parameters Do Not Determine Whether Muscle Sympathetic Nerve Activity Increases or Decreases During Pain.

    PubMed

    Kobuch, Sophie; Fazalbhoy, Azharuddin; Brown, Rachael; Macefield, Vaughan G

    2015-01-01

    We have previously reported that there are inter-individual differences in the cardiovascular responses to experimental muscle pain, which are consistent over time: intramuscular infusion of hypertonic saline, causing pain lasting ~60 min, increases muscle sympathetic nerve activity (MSNA)-as well as blood pressure and heart rate-in certain subjects, but decrease it in others. Here, we tested the hypothesis that baseline physiological parameters (resting MSNA, heart rate, blood pressure, heart rate variability) determine the cardiovascular responses to long-lasting muscle pain. MSNA was recorded from the common peroneal nerve, together with heart rate and blood pressure, during a 45-min intramuscular infusion of hypertonic saline solution into the tibialis anterior of 50 awake human subjects (25 females and 25 males). Twenty-four subjects showed a sustained increase in mean amplitude of MSNA (160.9 ± 7.3%), while 26 showed a sustained decrease (55.1 ± 3.5%). Between the increasing and decreasing groups there were no differences in baseline MSNA (19.0 ± 1.5 vs. 18.9 ± 1.2 bursts/min), mean BP (88.1 ± 5.2 vs. 88.0 ± 3.8 mmHg), HR (74.7 ± 2.0 vs. 72.8 ± 1.8 beats/min) or heart rate variability (LF/HF 1.8 ± 0.2 vs. 2.2 ± 0.3). Furthermore, neither sex nor body mass index had any effect on whether MSNA increased or decreased during tonic muscle pain. We conclude that the measured baseline physiological parameters cannot account for the divergent sympathetic responses during tonic muscle pain. PMID:26733786

  8. Inhibitory H3 receptors on sympathetic nerves of the pithed rat: activation by endogenous histamine and operation in spontaneously hypertensive rats.

    PubMed

    Godlewski, G; Malinowska, B; Buczko, W; Schlicker, E

    1997-02-01

    Our previous results demonstrate the occurrence of presynaptic inhibitory histamine H3 receptors on sympathetic neurons innervating resistance vessels of the pithed rat. The present study, in which new H3 receptor ligands with increased potency and selectivity (imetit, clobenpropit) were used, was designed to further explore the role of H3 receptors in the regulation of the rat cardiovascular system. In particular we were interested whether these receptors may be activated by endogenous histamine and whether they are detectable in an experimental model of hypertension. All experiments were performed on pithed and vagotomized rats treated with rauwolscine 1 mumol/kg. In normotensive Wistar rats the electrical (1 Hz, 1 ms, 50 V for 20 s) stimulation of the preganglionic sympathetic nerve fibres increased diastolic blood pressure by about 35 mmHg. Two H3 receptor agonists, R-(-)-alpha-methylhistamine and imetit, inhibited the electrically induced increase in diastolic blood pressure in a dose-dependent manner. The maximal effect (about 25%) was obtained for R-(-)-alpha-methylhistamine at about 10 mumol/kg and for imetit at about 1 mumol/kg. Two H3 receptor antagonists, thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg, attenuated the inhibitory effect of imetit. The neurogenic vasopressor response was increased by about 15% by thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg and decreased by 25% by the histamine methyltransferase inhibitor metoprine 37 mumol/kg. R-(-)-alpha-Methylhistamine, imetit, thioperamide, clobenpropit and metoprine did not affect the vasopressor response to exogenously added noradrenaline 0.01 mumol/kg (which increased diastolic blood pressure by about 40 mmHg). Metoprine had only a very low affinity for H3 binding sites (labelled by 3H-N alpha-methylhistamine; pKi 4.46). In pithed Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats, electrical (1 Hz, 1 ms, 50 V for 10 s) stimulation increased diastolic blood pressure by 28

  9. The role of adenosine A2A and A3 receptors on the differential modulation of norepinephrine and neuropeptide Y release from peripheral sympathetic nerve terminals.

    PubMed

    Donoso, M Verónica; Aedo, Felipe; Huidobro-Toro, J Pablo

    2006-03-01

    The pre-synaptic sympathetic modulator role of adenosine was assessed by studying transmitter release following electrical depolarization of nerve endings from the rat mesenteric artery. Mesentery perfusion with exogenous adenosine exclusively inhibited the release of norepinephrine (NA) but did not affect the overflow of neuropeptide Y (NPY), establishing the basis for a differential pre-synaptic modulator mechanism. Several adenosine structural analogs mimicked adenosine's effect on NA release and their relative order of potency was: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride = 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-d-ribofuranuronamide = 5'-(N-ethylcarboxamido)adenosine > adenosine > N(6)-cyclopentyladenosine. The use of selective receptor subtype antagonists confirmed the involvement of A(2A) and A(3) adenosine receptors. The modulator role of adenosine is probably due to the activation of both receptors; co-application of 1 nM 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride plus 1 nM 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-D-ribofuranuronamide caused additive reductions in NA released. Furthermore, while 1 nM of an A(2A) or A(3) receptor antagonist only partially reduced the inhibitory action of adenosine, the combined co-application of the two antagonists fully blocked the adenosine-induced inhibition. Only the simultaneous blockade of the adenosine A(2A) plus A(3) receptors with selective antagonists elicited a significant increase in NA overflow. H 89 reduced the release of both NA and NPY. We conclude that pre-synaptic A(2A) and A(3) adenosine receptor activation modulates sympathetic co-transmission by exclusively inhibiting the release of NA without affecting immunoreactive (ir)-NPY and we suggest separate mechanisms for vesicular release modulation.

  10. Calibrated variability of muscle sympathetic nerve activity during graded head-up tilt in humans and its link with noradrenaline data and cardiovascular rhythms.

    PubMed

    Marchi, Andrea; Bari, Vlasta; De Maria, Beatrice; Esler, Murray; Lambert, Elisabeth; Baumert, Mathias; Porta, Alberto

    2016-06-01

    Muscle sympathetic nerve activity (MSNA) variability is traditionally computed through a low-pass filtering procedure that requires normalization. We proposed a new beat-to-beat MSNA variability computation that preserves dimensionality typical of an integrated neural discharge (i.e., bursts per unit of time). The calibrated MSNA (cMSNA) variability technique is contrasted with the traditional uncalibrated MSNA (ucMSNA) version. The powers of cMSNA and ucMSNA variabilities in the low-frequency (LF, from 0.04 to 0.15 Hz) band were computed with those of the heart period (HP) of systolic and diastolic arterial pressure (SAP and DAP, respectively) in seven healthy subjects (age, 20-28 years; median, 22 years; 5 women) during a graded head-up tilt. Subjects were sequentially tilted at 0°, 20°, 30°, 40°, and 60° table inclinations. The LF powers of ucMSNA and HP variabilities were expressed in normalized units (LFnu), whereas all remaining spectral markers were expressed in absolute units. We found that 1) the LF power of cMSNA variability was positively correlated with tilt angle, whereas the LFnu power of the ucMSNA series was uncorrelated; 2) the LF power of cMSNA variability was correlated with LF powers of SAP and DAP, LFnu power of HP and noradrenaline concentration, whereas the relationship of the LFnu power of ucMSNA variability to LF powers of SAP and DAP was weaker and that to LFnu power of HP was absent; and 3) the stronger relationship of cMSNA variability to SAP and DAP spectral markers compared with the ucMSNA series was confirmed individually. The cMSNA variability appears to be more suitable in describing sympathetic control in humans than traditional ucMSNA variability. PMID:27009053

  11. Sympathetic nerve activity in normal and cystic follicles from isolated bovine ovary: local effect of beta-adrenergic stimulation on steroid secretion

    PubMed Central

    2011-01-01

    Cystic ovarian disease (COD) is an important cause of abnormal estrous behavior and infertility in dairy cows. COD is mainly observed in high-yielding dairy cows during the first months post-partum, a period of high stress. We have previously reported that, in lower mammals, stress induces a cystic condition similar to the polycystic ovary syndrome in humans and that stress is a definitive component in the human pathology. To know if COD in cows is also associated with high sympathetic activity, we studied isolated small antral (5mm), preovulatory (10mm) and cystic follicles (25mm). Cystic follicles which present an area 600 fold greater compared with preovulatory follicles has only 10 times less concentration of NE as compared with small antral and preovulatory follicles but they had 10 times more NE in follicular fluid, suggesting a high efflux of neurotransmitter from the cyst wall. This suggestion was reinforced by the high basal release of recently taken-up 3H-NE found in cystic follicles. While lower levels of beta-adrenergic receptor were found in cystic follicles, there was a heightened response to the beta-adrenergic agonist isoproterenol and to hCG, as measured by testosterone secretion. There was however an unexpected capacity of the ovary in vitro to produce cortisol and to secrete it in response to hCG but not to isoproterenol. These data suggest that, during COD, the bovine ovary is under high sympathetic nerve activity that in addition to an increased response to hCG in cortisol secretion could participate in COD development. PMID:21575217

  12. Histamine H3-Receptor Signaling in Cardiac Sympathetic Nerves: Identification of a Novel MAPK-PLA2-COX-PGE2-EP3R Pathway

    PubMed Central

    Levi, Roberto; Seyedi, Nahid; Schaefer, Ulrich; Estephan, Rima; Mackins, Christina J.; Tyler, Eleanor; Silver, Randi B.

    2007-01-01

    We tested the hypothesis that the histamine H3-receptor (H3R)-mediated attenuation of norepinephrine (NE) exocytosis from cardiac sympathetic nerves results not only from a Gαi-mediated inhibition of the adenylyl cyclase-cAMP-PKA pathway, but also from a Gβγi-mediated activation of the MAPK-PLA2 cascade, culminating in formation of an arachidonate metabolite with anti-exocytotic characteristics (e.g., PGE2). We report in Langendorff-perfused guinea-pig hearts and isolated sympathetic nerve endings (cardiac synaptosomes), H3R-mediated attenuation of K+-induced NE exocytosis was prevented by MAPK and PLA2 inhibitors, and by cyclooxygenase and EP3-receptor (EP3R) antagonists. Moreover, H3R activation resulted in MAPK phosphorylation in H3R-transfected SH-SY5Y neuroblastoma cells, and in PLA2 activation and PGE2 production in cardiac synaptosomes; H3R-induced MAPK phosphorylation was prevented by an anti-βγ peptide. Synergism between H3R and EP3R agonists (i.e., imetit and sulprostone, respectively) suggested PGE2 may be a downstream effector of the anti-exocytotic effect of H3R activation. Furthermore, the anti-exocytotic effect of imetit and sulprostone was potentiated by the N-type Ca2+-channel antagonist ω-conotoxin GVIA, and prevented by an anti-Gβγ peptide. Our findings suggest an EP3R Gβγi-induced decrease in Ca2+ influx through N-type Ca2+-channels is involved in PGE2/EP3R-mediated attenuation of NE exocytosis elicited by H3R activation. Conceivably, activation of the Gβγi subunit of H3R and EP3R may also inhibit Ca2+ entry directly, independent of MAPK intervention. As heart failure, myocardial ischemia and arrhythmic dysfunction are associated with excessive local NE release, attenuation of NE release by H3R activation is cardioprotective. Thus, the uncovering of a novel H3R signaling pathway may ultimately bear therapeutic significance in hyper-adrenergic states. PMID:17266940

  13. Clinical Benefits of Systemic Chemotherapy for Patients with Metastatic Pheochromocytomas or Sympathetic Extra-Adrenal Paragangliomas: Insights from the Largest Single Institutional Experience

    PubMed Central

    Ayala-Ramirez, Montserrat; Feng, Lei; Habra, Mouhammed A.; Rich, Thereasa; Dickson, Paxton V.; Perrier, Nancy; Phan, Alexandria; Waguespack, Steven; Patel, Shreyaskumar; Jimenez, Camilo

    2013-01-01

    Background The purpose of this study was to evaluate the clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic paragangliomas by assessing reduction in tumor size, blood pressure, and improvement in overall survival. Methods We retrospectively reviewed the medical records of patients with metastatic pheochromocytomas-sympathetic paragangliomas who had received chemotherapy at The University of Texas MD Anderson Cancer Center Results Clinical benefit and overall survival (OS) were assessed. Of fifty-four patients treated with chemotherapy, fifty-two were evaluable for response. Seventeen (33%) experienced a response, defined as decreased or normalized blood pressure/decreased number and dosage of antihypertensive medications and/or reduced tumor size after the first chemotherapy regimen. The median OS time was 6.4 years (95 confidence interval (CI): 5.2–16.4) for responders and 3.7 (95% CI: 3.0–7.5) years for non-responders. Of patients who had synchronous metastatic disease, a positive response at 1 year after the start of chemotherapy was associated with a trend toward a longer overall survival (log-rank test, P-value =0.095). In a multivariate Cox proportional hazards model, the effect of response to chemotherapy on overall survival was significant (hazard ratio=0.22, 95% confidence interval: 0.05–1.0; P-value = 0.05). All responders had been treated with dacarbazine and cyclophosphamide. Vincristine was included for 14 responders and doxorubicin was included for 12 responders. We could not identify clinical factors that predicted response to chemotherapy. Conclusion Chemotherapy may decrease tumor size and facilitate blood pressure control in about 33% of patients with metastatic pheochromocytoma-sympathetic paraganglioma. These patients exhibit a longer survival. PMID:22006217

  14. Intragastric injection of Lactobacillus casei strain Shirota suppressed spleen sympathetic activation by central corticotrophin-releasing factor or peripheral 2-deoxy-d-glucose in anesthetized rats.

    PubMed

    Tanida, Mamoru; Takada, Mai; Kato-Kataoka, Akito; Kawai, Mitsuhisa; Miyazaki, Kouji; Shibamoto, Toshishige

    2016-04-21

    Intragastric (IG) administration of probiotic strain Lactobacillus casei Shirota (LcS) decreases the sympathetic nerve outflow of anesthetized rats in a tissue-specific manner. In the present study, we examined the effects of IG administration of LcS on sympathetic activation induced by an intracerebroventricular (ICV) injection of corticotrophin-releasing factor (CRF) and an intravenous (IV) injection of 2-deoxy-d-glucose (2DG) or interleukin (IL)-1β in urethane-anesthetized rats. The IG administration of LcS differently affected the stimulatory responses of sympathetic nerve outflow to CRF. LcS suppressed the increase in splenic sympathetic nerve activity (Spleen-SNA), induced by central CRF, in a dose-dependent manner; however, it did not alter adrenal sympathetic nervous activity (ASNA). In contrast, LcS did not affect spleen-SNA and ASNA following an IV injection of IL-1β. On the other hand, IG administration of LcS suppressed the activation of ASNA following an IV injection of 2DG. These findings suggest that the suppression of central CRF-induced sympathetic activation by LcS is tissue-specific. Moreover, it can suppress the 2DG-induced sympathetic activation. Furthermore, we found that stomach-specific vagotomy attenuates the suppressive effect of LcS on CRF-mediated spleen-SNA activation. Thus, the present study suggests that LcS administered to the stomach may act on the afferent vagal nerve and send afferent signals to the brain to regulate efferent SNA induced by sympathetic stimulators. PMID:26971699

  15. Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide Y inputs into the paraventricular nucleus in female rats.

    PubMed

    Cassaglia, Priscila A; Shi, Zhigang; Brooks, Virginia L

    2016-07-01

    Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α-MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R. PMID:27122366

  16. Differential effects of enalapril-felodipine versus enalapril-lercanidipine combination drug treatment on sympathetic nerve traffic and metabolic profile in obesity-related hypertension.

    PubMed

    Seravalle, Gino; Brambilla, Gianmaria; Pizzalla, Daniela Prata; Casati, Anna; Riva, Marta; Cuspidi, Cesare; Bombelli, Michele; Mancia, Giuseppe; Grassi, Guido

    2016-03-01

    Scanty information is available on the effects of combination drug treatment based on an ACE inhibitor and a calcium channel blocker on the neurometabolic alterations characterizing obesity-related hypertension (OHT). After 2-week run-in with enalapril (20 mg), 36 OHTs were randomized according to a double-blind crossover design to a combination therapy with either lercanidipine 10 mg (L) or felodipine extended release 5 mg (F), each lasting 8 weeks. Measurements included clinic and ambulatory blood pressure (BP) and heart rate, homeostasis model assessment index, plasma norepinephrine, and muscle sympathetic nerve activity. Patients with uncontrolled BP were then uptitrated to 20 mg/d (L) and 10 mg/d (F) combined with enalapril 20 mg, respectively, for further 8 weeks. For similar BP reductions, enalapril-lercanidipine (EL) caused norepinephrine and MSNA increases significantly less pronounced than those seen with enalapril-felodipine, the lesser sympathoexcitation observed with EL being coupled with a significant improvement in homeostasis model assessment index. This was the case also when L and F were uptitrated in the combination. In OHT, at variance from enalapril-felodipine, EL combination is almost entirely devoid of any major sympathoexcitatory effect and is associated with an improvement in insulin sensitivity. PMID:26831124

  17. Adrenal Insufficiency

    MedlinePlus

    ... What is adrenal insufficiency? Did you know? The adrenal glands, located on top of the kidneys, make hormones ... body functions. The outer layer (cortex) of the adrenal glands makes three types of steroid hormones. In adrenal ...

  18. [An experimental study of the effect of an artichoke preparation on the activity of the sympathetic-adrenal system in carbon disulfide exposure].

    PubMed

    Khalkova, Zh; Vangelova, K; Zaĭkov, Kh

    1995-01-01

    Artichoke, a new Bulgarian preparation based on the plant Cynara scolymus, was tested for influence on sympatho-adrenal system (SAS) activity in experimental inhalation exposure to carbon disulfide. This chronic (six-month) inhalation experiment was done on Wistar albino rats of either sex. Activity of SAS was assessed through excretion of noradrenalin and adrenalin. Findings indicated a phasic SAS response depending on concentration and duration of carbon disulfide exposure. With exposure to 30 mg.m3, SAS activity was observed to decrease in the second month, followed by increase in the fourth and sixth months. With exposure to 300 mg.m3, SAS activity was elevated over the whole period of study. Under the influence of the preparation artichoke at dosage 200 mg.kg-1, catecholamines, increased by carbon disulfide exposure, returned to normal. This trend was more marked for noradrenalin.

  19. Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat.

    PubMed Central

    Baker, D G; Coleridge, H M; Coleridge, J C; Nerdrum, T

    1980-01-01

    1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain. 2. In anaesthetized cats, we recorded afferent impulses from 'single-fibre' slips of the left 2nd--5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 . 1--1 . 0 microgram/ml.) locally to the site of the ending; we also injected bradykinin (0 . 3--1 . 0 microgram/kg) into the left atrium. 3. Afferent endings excited by bradykinin (159 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with A delta of C fibres (mean conduction velocity, 7 . 5 +/- 0 . 6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume. 4. Bradykinin increased mechanoreceptor firing from 0 . 7 +/- to 5 . 0 +/- 0 . 3 (mean +/- S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle. 5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A delta fibres (mean conduction velocity, 2 . 3 +/- 0 . 7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0 . 6 to 15 . 6 +/- 1 . 3 impulses/sec and

  20. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin.

    PubMed

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-11-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  1. Endogenous nitric oxide derived from NOS I or II in thoracic spinal cord exerts opposing tonic modulation on sympathetic vasomotor tone via disparate mechanisms in anesthetized rats.

    PubMed

    Poon, Yan-Yuen; Tsai, Ching-Yi; Cheng, Chung-Dar; Chang, Alice Y W; Chan, Samuel H H

    2016-09-01

    The sympathetic preganglionic neurons (SPN) in the thoracic spinal cord regulate vasomotor tone via norepinephrine released from sympathetic terminals and adrenal medulla. We assessed the hypothesis that nitric oxide synthase I (NOS I)- and NOS II-derived nitric oxide (NO) in the thoracic spinal cord differentially modulate sympathetic outflow and that the adrenal medulla may be involved in those modulatory actions. In Sprague-Dawley rats, NOS I immunoreactivity was distributed primarily in the perikaryon, proximal dendrites, or axons of SPN, and small clusters of NOS II immunoreactivity impinged mainly on the circumference of SPN. Intrathecal administration of 7-nitroindazole (7-NI), a specific NOS I antagonist, into the thoracic spinal cord significantly reduced arterial pressure, heart rate, and basal or baroreflex-mediated sympathetic vasomotor tone. On the other hand, intrathecal application of S-methylisothiourea (SMT), a specific NOS II antagonist, elevated arterial pressure with a transient reduction of heart rate, induced a surge of plasma norepinephrine, and reduced baroreflex-mediated but not basal sympathetic vasomotor tone. Bilateral adrenalectomy significantly exacerbated the cardiovascular responses to 7-NI but antagonized those to SMT. We conclude that both NOS I and NOS II are present in the thoracic spinal cord and are tonically active under physiological conditions. Furthermore, the endogenous NO generated by NOS I-containing SPN exerts a tonic excitatory action on vasomotor tone mediated by norepinephrine released from the adrenal medulla and sympathetic nerve terminals. On the other hand, NO derived from NOS II exerts a tonic inhibitory action on sympathetic outflow from the SPN that targets primarily the blood vessels. PMID:27371683

  2. [Correlation between sympathetic nervous activity of the skin and local temperature of skin projections of the spinal nerves in the course of rehabilitation of the patients presenting with dorsopathies].

    PubMed

    Boĭtsov, I V

    2014-01-01

    We undertook the correlation analysis of the parameters characterizing the intensity of the skin sympathetic reactions and local temperature of skin projections of the spinal nerves in three groups of patients presenting with dorsopathies and differing in terms of sympathetic regulation of the microvasculature. It was shown that the patients of group 1 exhibited positive correlation between the above parameters (preserved vegetative regulation of microcirculation despite the tendency toward its atonic-stagnant disturbances). The patients of group 2 showed negative correlation between these parameters (preserved vegetative regulation of microcirculation despite the tendency toward its spastic-stagnant disturbances). Neither one nor the other type of correlation was documented in the patients of group 3 which suggests the absence of vegetative regulation of the microcirculatory bed.

  3. GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens.

    PubMed

    Lymperopoulos, Anastasios; Brill, Ava; McCrink, Katie A

    2016-08-01

    The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as "presynaptic autoreceptors" in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the α2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and β-arrestins in these processes and particular points of focus for future research will be highlighted, as well.

  4. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    PubMed

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists.

  5. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    PubMed

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists. PMID:25063794

  6. Genetics of adrenal tumors.

    PubMed

    Opocher, G; Schiavi, F; Cicala, M V; Patalano, A; Mariniello, B; Boaretto, F; Zovato, S; Pignataro, V; Macino, B; Negro, I; Mantero, F

    2009-06-01

    The impact of genetics and genomics on clinical medicine is becoming more and more important. Endocrinology pioneered the development of molecular medicine, but also the study of adrenal tumors had a great impact in this field. Particularly important was the detection of genetics of tumors derived from the adrenal medulla, as well as that of those derived from the sympathetic and parasympathetic paraganglia. The identification of mutations in one of the several pheochromocytoma/paraganglioma susceptibility genes may indicate a specific clinical management drive. Less well understood is the genetics of adrenal cortex tumors, in particular adrenocortical carcinoma, a rare and particularly aggressive disease. There are only a few examples of hereditary transmission of adrenocortical carcinoma, but the analysis of low penetrance genes by genome wide association study may enable us to discover new genetic mechanisms responsible for adrenocortical-derived tumors. PMID:19471236

  7. Spatial and activity-dependent catecholamine release in rat adrenal medulla under native neuronal stimulation.

    PubMed

    Wolf, Kyle; Zarkua, Georgy; Chan, Shyue-An; Sridhar, Arun; Smith, Corey

    2016-09-01

    Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions of the sympathetic splanchnic nerve. Upon synaptic stimulation, the adrenal medulla releases the catecholamines, epinephrine, and norepinephrine into the suprarenal vein for circulation throughout the body. Under sympathetic tone, catecholamine release is modest. However, upon activation of the sympathoadrenal stress reflex, and increased splanchnic firing, adrenal catecholamine output increases dramatically. Moreover, specific stressors can preferentially increase release of either epinephrine (i.e., hypoglycemia) or norepinephrine (i.e., cold stress). The mechanism for this stressor-dependent segregated release of catecholamine species is not yet fully understood. We tested the hypothesis that stimulation of either division of the splanchnic selects for epinephrine over norepinephrine release. We introduce an ex vivo rat preparation that maintains native splanchnic innervation of the adrenal gland and we document experimental advantages and limitations of this preparation. We utilize fast scanning cyclic voltammetry to detect release of both epinephrine and norepinephrine from the adrenal medulla, and report that epinephrine and norepinephrine release are regulated spatially and in a frequency-dependent manner. We provide data to show that epinephrine is secreted preferentially from the periphery of the medulla and exhibits a higher threshold and steeper stimulus-secretion function than norepinephrine. Elevated stimulation of the whole nerve specifically enhances epinephrine release from the peripheral medulla. Our data further show that elimination of either division from stimulation greatly attenuated epinephrine release under elevated stimulation, while either division alone can largely support norepinephrine release. PMID:27597763

  8. Comparative effects of long-acting and short-acting loop diuretics on cardiac sympathetic nerve activity in patients with chronic heart failure

    PubMed Central

    Matsuo, Yae; Kasama, Shu; Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Ichikawa, Shuichi; Suzuki, Yasuyuki; Matsumoto, Naoya; Sato, Yuichi; Kurabayashi, Masahiko

    2016-01-01

    Objective Short-acting loop diuretics are known to enhance cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF). The effects of two loop diuretics—long-acting azosemide and short-acting furosemide—on CSNA were evaluated using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with CHF. Methods The present study was a subanalysis of our previously published study, which had reported that serial 123I-MIBG studies were the most useful prognostic indicator in patients with CHF. Patients with CHF (n=208, left ventricular ejection fraction <45%) but no history of cardiac events for at least 5 months prior to the study were identified according to their histories of acute decompensated heart failure requiring hospitalisation. Patients underwent 123I-MIBG scintigraphy immediately before hospital discharge and at a 6-month follow-up. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio and washout rate (WR) were determined using 123I-MIBG scintigraphy. A total of 108 patients were selected, and propensity score matching was used to compare patients treated with either oral azosemide (n=54) or furosemide (n=54). Results After treatment, 123I-MIBG scintigraphic parameters improved in both groups. However, the degree of change in % denervation was −13.8±10.5 in the azosemide group and −5.7±12.7 in the furosemide group (p<0.01), the change in H/M ratio was 0.20±0.16 in the azosemide group and 0.06±0.19 in the furosemide group (p<0.01), and the change in WR was −11.3±9.2% in the azosemide group and −3.0±12.7% in the furosemide group (p<0.01). Moreover, multivariate analysis showed an independent and significant positive relationship between furosemide and δ-WR from hospital discharge to 6 months after treatment in patients with CHF (p=0.001). Conclusions These findings indicate that azosemide suppresses CSNA compared with furosemide in patients with CHF. Trial registration number UMIN000000626

  9. Adrenal glands

    MedlinePlus

    ... disorders , infections, tumors, and bleeding. Related topics: Addison disease Adrenal insufficiency Congenital adrenal hyperplasia Cushing syndrome Diabetes mellitus - secondary Glucocorticoid medications Hirsutism Hump ...

  10. Localized sympathetic overactivity: an uncommon complication of lung cancer.

    PubMed

    Walsh, J C; Low, P A; Allsop, J L

    1976-01-01

    Direct nerve infiltration by tumour tissue usually produces pain, and loss of motor, sensory, and autonomic function. Two patients are reported in whom a major symptom of nerve infiltration was sympathetic overactivity manifested by excessive spontaneous sweating. PMID:1255218

  11. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  12. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  13. Sympathetic innervation of human muscle spindles

    PubMed Central

    Radovanovic, Dina; Peikert, Kevin; Lindström, Mona; Domellöf, Fatima Pedrosa

    2015-01-01

    The aim of the present study was to investigate the presence of sympathetic innervation in human muscle spindles, using antibodies against neuropeptide Y (NPY), NPY receptors and tyrosine hydroxylase (TH). A total of 232 muscle spindles were immunohistochemically examined. NPY and NPY receptors were found on the intrafusal fibers, on the blood vessels supplying muscle spindles and on free nerve endings in the periaxial space. TH-immunoreactivity was present mainly in the spindle nerve and vessel. This is, to our knowledge, the first morphological study concerning the sympathetic innervation of the human muscle spindles. The results provide anatomical evidence for direct sympathetic innervation of the intrafusal fibers and show that sympathetic innervation is not restricted to the blood vessels supplying spindles. Knowledge about direct sympathetic innervation of the muscle spindle might expand our understanding of motor and proprioceptive dysfunction under stress conditions, for example, chronic muscle pain syndromes. PMID:25994126

  14. Sympathetic orchidopathia.

    PubMed Central

    Williamson, R. C.; Thomas, W. E.

    1984-01-01

    Subfertility has recently been shown to follow unilateral torsion of the spermatic cord in more than half the patients studied. Since the anatomical anomaly that predisposes to torsion (a high investment of the tunica vaginalis) is commonly bilateral, there could be an associated congenital defect in spermatogenesis on each side. Alternatively, autoantigens escaping from the ischaemic or 'exciting' testis could trigger an immunological response which damages the contralateral or 'sympathising' testis. Demonstration of an autoallergic (sympathetic) orchidopathia, analogous to sympathetic ophthalmia, would fundamentally alter the management of testicular torsion. PMID:6742739

  15. Adrenal insufficiency.

    PubMed

    Li-Ng, Melissa; Kennedy, Laurence

    2012-10-01

    Adrenocortical insufficiency may arise through primary failure of the adrenal glands or due to lack of ACTH stimulation as a result of pituitary or hypothalamic dysfunction. Prolonged administration of exogenous steroids will suppress the hypothalamic-pituitary-adrenal axis, and hence cortisol secretion. We review briefly the causes, investigation, and treatment of adrenal insufficiency, and highlight aspects of particular relevance to patients with adrenal tumors.

  16. Atropine-resistant effects of the muscarinic agonists McN-A-343 and AHR 602 on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart

    PubMed Central

    Fozard, J.R.; Muscholl, E.

    1974-01-01

    1 The effects of 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) and N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) on cardiac performance and noradrenaline release from terminal sympathetic fibres were measured in isolated perfused hearts of rabbits. 2 In the presence of sufficient atropine to block muscarinic receptors, high concentrations of McN-A-343 and AHR 602 caused no cardiac stimulation and there was no increase in the resting output of noradrenaline into the perfusates. 3 McN-A-343 and AHR 602 increased both the mechanical responses and the transmitter overflow evoked by electrical stimulation of the sympathetic nerves (SNS) but inhibited both parameters during perfusion with 1,1-dimethyl-4-phenylpiperazinium (DMPP). The effects were atropine-resistant and qualitatively similar to those seen with cocaine. Hexamethonium inhibited DMPP, but affected neither SNS per se nor the facilitatory effects of McN-A-343 and AHR 602 on SNS. 4 McN-A-343, cocaine and desipramine (but not AHR 602 or hexamethonium) blocked the net cardiac noradrenaline uptake and increased the positive chronotropic effect of noradrenaline. 5 Prior perfusion with concentrations of cocaine and desipramine sufficient to block uptake reduced or abolished the facilitatory effects of both McN-A-343 and AHR 602 on SNS. 6 Cocaine, McN-A-343 and AHR 602 displayed local anaesthetic properties on the guinea-pig wheal and frog nerve plexus tests, and their relative potencies in this respect were similar to those for inhibition of DMPP-evoked transmitter overflow. Hexamethonium did not produce local anaesthesia. 7 The results indicate that the facilitated release of noradrenaline after SNS and the inhibition of release after DMPP produced by McN-A-343 and AHR 602 are the result of their combined local anaesthetic action and inhibition of amine uptake. PMID:4447857

  17. NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

    PubMed

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2015-07-01

    Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism.

  18. NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

    PubMed

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2015-07-01

    Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism. PMID:25910812

  19. Netrin-1 controls sympathetic arterial innervation

    PubMed Central

    Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J.C.; Kennedy, Timothy E.; Zhuang, Zhen; Simons, Michael; Levy, Bernard I.; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

    2014-01-01

    Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type–specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs. PMID:24937433

  20. Isolation of neural crest derived chromaffin progenitors from adult adrenal medulla.

    PubMed

    Chung, Kuei-Fang; Sicard, Flavie; Vukicevic, Vladimir; Hermann, Andreas; Storch, Alexander; Huttner, Wieland B; Bornstein, Stefan R; Ehrhart-Bornstein, Monika

    2009-10-01

    Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Unlike the closely-related sympathetic neurons, a subpopulation of proliferation-competent cells exists even in the adult. Here, we describe the isolation, expansion, and in vitro characterization of proliferation-competent progenitor cells from the bovine adrenal medulla. Similar to neurospheres, these cells, when prevented from adherence to the culture dish, grew in spheres, which we named chromospheres. These chromospheres were devoid of mRNA specific for smooth muscle cells (MYH11) or endothelial cells (PECAM1). During sphere formation, markers for differentiated chromaffin cells, such as phenylethanolamine-N-methyl transferase, were downregulated while neural progenitor markers nestin, vimentin, musashi 1, and nerve growth factor receptor, as well as markers of neural crest progenitor cells such as Sox1 and Sox9, were upregulated. Clonal analysis and bromo-2'-deoxyuridine-incorporation analysis demonstrated the self-renewing capacity of chromosphere cells. Differentiation protocols using NGF and BMP4 or dexamethasone induced neuronal or endocrine differentiation, respectively. Electrophysiological analyses of neural cells derived from chromospheres revealed functional properties of mature nerve cells, such as tetrodotoxin-sensitive sodium channels and action potentials. Our study provides evidence that proliferation and differentiation competent chromaffin progenitor cells can be isolated from adult adrenal medulla and that these cells might harbor the potential for the treatment of neurodegenerative diseases, such as Parkinson's disease. PMID:19609938

  1. Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response.

    PubMed

    Jansen, A S; Nguyen, X V; Karpitskiy, V; Mettenleiter, T C; Loewy, A D

    1995-10-27

    During stress, the activity of the sympathetic nervous system is changed in a global fashion, leading to an increase in cardiovascular function and a release of adrenal catecholamines. This response is thought to be regulated by a common set of brain neurons that provide a dual input to the sympathetic preganglionic neurons regulating cardiac and adrenal medullary functions. By using a double-virus transneuronal labeling technique, the existence of such a set of central autonomic neurons in the hypothalamus and brainstem was demonstrated. These neurons innervate both of the sympathetic outflow systems and likely function in circumstances where parallel sympathetic processing occurs, such as in the fight-or-flight response.

  2. The sympathetic nervous system in hypertension: back to the future?

    PubMed

    Esler, Murray

    2015-02-01

    The seventeenth century London neuroanatomical school headed by Thomas Willis published the first images of the sympathetic nervous system. Nineteenth century European physiologists characterised these as the "pressor nerves". Von Euler's demonstration that the sympathetic transmitter was norepinephrine brought the field into the modern era. Sympathetic nervous system responses are regionally differentiated; human regional sympathetic activity is best studied by recording from postganglionic sympathetic efferents directed to the skeletal muscle vasculature (clinical microneurography) and by measurement of organ-specific norepinephrine release to plasma from sympathetic nerves (regional "norepinephrine spillover"). With these techniques, the sympathetic nervous system became accessible to clinical scientists, allowing the demonstration that sympathetic nervous system activation is crucial in the development and outcomes of cardiovascular disorders, most notably heart failure and essential hypertension. Activation of the renal sympathetic outflow is pivotal in the pathogenesis of essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. Although disputed, the case is strong that in hypertension, we are now on the cusp of effective "mechanisms to management" transition, with the use of catheter-based renal sympathetic nerve ablation for treating drug-resistant hypertension.

  3. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  4. Reflex sympathetic dystrophies and algodystrophies: historical and pathogenic considerations.

    PubMed

    Procacci, P; Maresca, M

    1987-11-01

    This paper reviews the historical development of the concepts of 'sympathy' of organs and of the sympathetic nervous system. In particular, the afferent function of the sympathetic system is discussed. The attention is focussed on sympathetic reflex dystrophies, known in some European schools as 'algodystrophies'. The pathogenic mechanisms of these affections, especially of causalgia, are discussed, considering the importance of peripheral damage to nerves, lateralisation of pain, 'mirror phenomena', and the relationship between peripheral and central mechanisms of pain.

  5. Neural control of adrenal medullary and cortical blood flow during hemorrhage

    SciTech Connect

    Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

    1987-03-01

    Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with /sup 153/Gd, /sup 114/In, /sup 113/Sn, /sup 103/Ru, /sup 95/Nb or /sup 46/Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.

  6. Adrenal adrenoceptors in heart failure

    PubMed Central

    de Lucia, Claudio; Femminella, Grazia D.; Gambino, Giuseppina; Pagano, Gennaro; Allocca, Elena; Rengo, Carlo; Silvestri, Candida; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2014-01-01

    Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CA) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being used for the treatment of this disease. Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin cell membranes. This process is regulated by adrenergic receptors (ARs): α2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and β ARs (mainly β2ARs) stimulate CA release through coupling to stimulatory Gs-proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs) regulate their signaling and function. Adrenal GRK2-mediated α2AR desensitization and downregulation are increased in HF and seem to be a fundamental regulator of CA secretion from the adrenal gland. Consequently, restoration of adrenal α2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF. This strategy could have several significant advantages over existing HF pharmacotherapies minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin–angiotensin–aldosterone and endothelin systems. The role of adrenal ARs in regulation of sympathetic hyperactivity opens interesting perspectives in understanding HF pathophysiology and in the identification of new therapeutic targets. PMID:25071591

  7. Adrenal myelolipoma.

    PubMed

    Cyran, K M; Kenney, P J; Memel, D S; Yacoub, I

    1996-02-01

    In 1905, Gierke [1] first described the occurrence of a tumor in the adrenal composed of mature fat and mixed myeloid and erythroid cells, subsequently termed "formations myelolipomatoses" by Oberling [2] in 1929. PMID:8553954

  8. Embryologic development of rat adrenal medulla in transplants to the anterior chamber of the eye.

    PubMed

    Unsicker, K

    1985-04-01

    The morphological development and plasticity of embryonic and postnatal rat adrenal medullary cells were studied in homologous adrenal grafts to the anterior chamber of the eye. The eyes of recipient rats were adrenergically denervated 10 days prior to grafting by extirpation of the superior cervical ganglion in order to increase levels of NGF and NGF-like activities in the iris. Grafts taken at the 15th day of embryonic development (E15), i.e., at the beginning of immigration of medullary progenitor cells into the adrenal cortical anlagen, contained no cortical or mature medullary cells after 2 weeks in oculo. Numerous sympathoblastic cells, however, were located at the anterior surface of the iris. E 16 and E 17 transplants showed abundant mature cortical tissue after 2 weeks. Small groups of medullary cells with the ultrastructural characteristics of mature pheochromoblasts or young chromaffin cells were interspersed among cortical cells without forming a discrete medulla. Neuronal cells were exclusively found outside the cortical cell mass. Sympathoblasts grew at the surface of the iris, while young sympathetic nerve cells, which were invested by Schwann cells and received synaptic axon terminals, were embedded into the stroma of the iris. Grafting of E 21 adrenals yielded very similar results except that, in a few instances, young chromaffin cells were located outside the cortex and sympathetic nerve cells were seen to be in close contact with cortical cells. In transplants of adult medullary cells typical mature adrenaline and noradrenaline cells were clearly distinguishable after 8 weeks even in the absence of cortical cells. The only indication of phenotypical changes in these cells was the formation by some of them, of neuritic processes which could be visualized in glyoxylic acid-treated whole mounts of irises. These results are compatible with the idea that embryonic adrenal medullary cells have the environmentally controlled potential to develop along

  9. Laparoscopic Resection of an Adrenal Schwannoma

    PubMed Central

    Konstantinos, Toutouzas G.; Panagiotis, Kekis B.; Nikolaos, Michalopoulos V.; Ioannis, Flessas; Andreas, Manouras; Geogrios, Zografos

    2012-01-01

    Background and Objectives: Schwannomas are tumors originating from Schwann cells of the peripheral nerve sheath (neurilemma) of the neuroectoderm. Rarely, schwannomas can arise from the retroperitoneum and adrenal medulla. We describe a case of a 71-y-old woman who presented with an incidentally discovered adrenal tumor. Methods: Ultrasound and computed tomography scans revealed a lesion with solid and cystic areas originating from the left adrenal gland. The patient underwent complete laparoscopic resection of the tumor and the left adrenal gland. Results: Histopathological examination and immunohistochemical staining of the excised specimen revealed a benign schwannoma measuring 5.5×5×3.7 cm. To our knowledge, few other cases of laparoscopic resection of adrenal schwannomas have been reported. Conclusion: Because preoperative diagnosis of adrenal tumors is inconclusive, complete laparoscopic excision allows for definitive diagnosis with histological evaluation and represents the treatment of choice. PMID:23484583

  10. Differential role of nitric oxide in regional sympathetic responses to stimulation of NTS A2a adenosine receptors.

    PubMed

    Scislo, Tadeusz J; Tan, Nobusuke; O'Leary, Donal S

    2005-02-01

    Our previous studies showed that preganglionic adrenal (pre-ASNA), renal (RSNA), lumbar, and postganglionic adrenal sympathetic nerve activities (post-ASNA) are inhibited after stimulation of arterial baroreceptors, nucleus of the solitary tract (NTS), and glutamatergic and P2x receptors and are activated after stimulation of adenosine A1 receptors. However, stimulation of adenosine A2a receptors inhibited RSNA and post-ASNA, whereas it activated pre-ASNA. Because the effects evoked by NTS A2a receptors may be mediated via activation of nitric oxide (NO) mechanisms in NTS neurons, we tested the hypothesis that NO synthase (NOS) inhibitors would attenuate regional sympathetic responses to NTS A2a receptor stimulation, whereas NO donors would evoke contrasting responses from pre-ASNA versus RSNA and post-ASNA. Therefore, in chloralose/urethane-anesthetized rats, we compared hemodynamic and regional sympathetic responses to microinjections of selective A2a receptor agonist (CGS-21680, 20 pmol/50 nl) after pretreatment with NOS inhibitors Nomega-nitro-L-arginine methyl ester (10 nmol/100 nl) and 1-[2-(trifluoromethyl)phenyl]imidazole (100 pmol/100 nl) versus pretreatment with vehicle (100 nl). In addition, responses to microinjections into the NTS of different NO donors [40 and 400 pmol/50 nl sodium nitroprusside (SNP); 0.5 and 5 nmol/50 nl 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA NONOate, also known as NOC-18), and 2 nmol/50 nl 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PAPA NONOate, also known as NOC-15)], the NO precursor L-arginine (10-50 nmol/50 nl), and sodium glutamate (500 pmol/50 nl) were evaluated. SNP, DETA NONOate, and PAPA NONOate activated pre-ASNA and inhibited RSNA and post-ASNA, whereas l-arginine and glutamate microinjected into the same site of the NTS inhibited all these sympathetic outputs. Decreases in heart rate and depressor or biphasic responses accompanied the neural responses. Pretreatment with NOS inhibitors

  11. 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.

  12. Autonomic control of adrenal function.

    PubMed Central

    Edwards, A V; Jones, C T

    1993-01-01

    Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

  13. The Human Sympathetic Nervous System Response to Spaceflight

    NASA Technical Reports Server (NTRS)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

    2003-01-01

    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  14. Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope

    NASA Technical Reports Server (NTRS)

    Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.; Beightol, L. A.; Hoag, J. B.; Tahvanainen, K. U.; Kuusela, T. A.; Diedrich, A. M.

    1997-01-01

    BACKGROUND: Autonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope. METHODS AND RESULTS: We studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening. CONCLUSIONS: Patients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.

  15. [Adrenal mass and adrenal insufficiency].

    PubMed

    Martínez Albaladejo, M; García López, B; Serrano Corredor, S; Alguacil García, G

    1996-12-01

    Primary adrenal insufficiency is a non frequent disease, that is declared in young adults and in the most of the cases is produced from an autoimmune mechanism or a tuberculous disease. The incidence of these forms in the different geographic areas is dependent of degree of irradication of the tuberculosis. We report the case of a patient with latent chronic adrenal insufficiency of tuberculous origin who was affected for an addisonian crisis during an intercurrent infectious disease, which permitted the diagnosis of the addisonian crisis, and Mal of Pott was moreover detected. Evolution with corticosteroid and specific treatment was very favorable.

  16. Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats

    PubMed Central

    Veitenheimer, Britta J.; Engeland, William C.; Guzman, Pilar A.; Fink, Gregory D.

    2012-01-01

    Forty-eight hours of water deprivation (WD) in conscious rats results in a paradoxical increase in mean arterial pressure (MAP). Previous studies suggest this may be due to increased sympathetic nerve activity (SNA). However, this remains to be investigated in conscious, freely behaving animals. The purpose of this study was to determine, in conscious rats, the role of the sympathetic nervous system (SNS) in mediating WD-induced increases in MAP and to identify which vascular beds are targeted by increased SNA. Each rat was chronically instrumented with a radiotelemetry transmitter to measure MAP and heart rate (HR) and an indwelling venous catheter for plasma sampling and/or drug delivery. MAP and HR were continuously measured during a 2-day baseline period followed by 48 h of WD and then a recovery period. By the end of the WD period, MAP increased by ∼15 mmHg in control groups, whereas HR did not change significantly. Chronic blockade of α1/β1-adrenergic receptors significantly attenuated the WD-induced increase in MAP, suggesting a role for global activation of the SNS. However, the MAP response to WD was unaffected by selective denervations of the hindlimb, renal, or splanchnic vascular beds, or by adrenal demedullation. In contrast, complete adrenalectomy (with corticosterone and aldosterone replaced) significantly attenuated the MAP response to WD in the same time frame as α1/β1-adrenergic receptor blockade. These results suggest that, in conscious water-deprived rats, the SNS contributes to the MAP response and may be linked to release of adrenocortical hormones. Finally, this sympathetically mediated response is not dependent on increased SNA to one specific vascular bed. PMID:22904160

  17. Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.

    PubMed

    Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

    2014-10-01

    This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables. PMID:25002406

  18. Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.

    PubMed

    Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

    2014-10-01

    This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables.

  19. Management of hypertension by reduction in sympathetic activity.

    PubMed

    Mathias, C J

    1991-04-01

    The sympathetic nervous system may initiate or maintain hypertension, and a range of approaches that reduce sympathetic activity is often of value in management. These may include nonpharmacological methods, such as the various forms of behavioral therapy (e.g., meditation, relaxation, and biofeedback techniques); weight reduction and avoidance of particular foods and agents that stimulate sympathetic activity (including caffeine and alcohol), and regular physical exercise. Pharmacological therapy includes centrally acting drugs such as alpha-methyldopa, clonidine, and reserpine; ganglionic blockers such as hexamethonium; agents acting on sympathetic nerve terminals such as guanethidine and debrisoquine; and drugs that may act at multiple sites, such as the beta-adrenergic blockers. The role of reducing sympathetic activity in the current management of hypertension and its complications is considered in this overview.

  20. Increased Catecholamine Secretion from Single Adrenal Chromaffin Cells in DOCA-Salt Hypertension Is Associated with Potassium Channel Dysfunction

    PubMed Central

    2013-01-01

    The mechanism of catecholamine release from single adrenal chromaffin cells isolated from normotensive and DOCA-salt hypertensive rats was investigated. These cells were used as a model for sympathetic nerves to better understand how exocytotic release of catecholamines is altered in this model of hypertension. Catecholamine secretion was evoked by local application of acetylcholine (1 mM) or high K+ (70 mM), and continuous amperometry was used to monitor catecholamine secretion as an oxidative current. The total number of catecholamine molecules secreted from a vesicle, the total number of vesicles fusing and secreting, and the duration of secretion in response to a stimulus were all significantly greater for chromaffin cells from hypertensive rats as compared to normotensive controls. The greater catecholamine secretion from DOCA-salt cells results, at least in part, from functionally impaired large conductance, Ca2+-activated (BK) and ATP-sensitive K+ channels. This work reveals that there is altered vesicular release of catecholamines from these cells (and possibly from perivascular sympathetic nerves) and this may contribute to increased vasomotor tone in DOCA-salt hypertension. PMID:23937098

  1. Sympathetic neural influence on bone metabolism in microgravity (Review).

    PubMed

    Mano, Tadaaki; Nishimura, N; Iwase, S

    2010-12-01

    Bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space and also for bedridden elderly people. Recent studies have indicated that the sympathetic nervous system plays a role in bone metabolism. This paper reviews findings concerning with sympathetic influences on bone metabolism to hypothesize the mechanism how sympathetic neural functions are related to bone loss in microgravity. Animal studies have suggested that leptin stimulates hypothalamus increasing sympathetic outflow to bone and enhances bone resorption through noradrenaline and β-adrenoreceptors in bone. In humans, even though there have been some controversial findings, use of β-adrenoblockers has been reported to be beneficial for prevention of osteoporosis and bone fracture. On the other hand, microneurographically-recorded sympathetic nerve activity was enhanced by exposure to microgravity in space as well as dry immersion or long-term bed rest to simulate microgravity. The same sympathetic activity became higher in elderly people whose bone mass becomes generally reduced. Our recent findings indicated a significant correlation between muscle sympathetic nerve activity and urinary deoxypyridinoline as a specific marker measuring bone resorption. Based on these findings we would like to propose a following hypothesis concerning the sympathetic involvement in the mechanism of bone loss in microgravity: An exposure to prolonged microgravity may enhance sympathetic neural traffic not only to muscle but also to bone. This sympathetic enhancement increases plasma noradrenaline level and inhibits osteogenesis and facilitates bone resorption through β-adrenoreceptors in bone to facilitate bone resorption to reduce bone mass. The use of β-adrenoblockers to prevent bone loss in microgravity may be reasonable.

  2. Secondary sympathetic chain reconstruction after endoscopic thoracic sympathicotomy.

    PubMed

    Telaranta, T

    1998-01-01

    Thoracoscopic sympathicotomy by electrocautery is an irreversible procedure. Thus the indications must be meticulously considered before the final decision to operate is taken by both the surgeon and the patient. All possible side effects should be dealt with and written informed consent required. A case of an open nerve reconstruction of the divided sympathetic chains is presented. One year after the reconstruction the patient reported subjective relief of the compensatory oversweating and restoration of sweating in the face and the armpit. Reversible methods like clipping the sympathetic chain should be considered whenever feasible instead of the irreversible electrocoagulation of the sympathetic chain. PMID:9641379

  3. 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

  4. Regional epinephrine kinetics in human heart failure: evidence for extra-adrenal, nonneural release.

    PubMed

    Kaye, D M; Lefkovits, J; Cox, H; Lambert, G; Jennings, G; Turner, A; Esler, M D

    1995-07-01

    A number of neurohumoral processes are activated in heart failure, including an increase in the plasma concentration of epinephrine. Radiotracer methods were applied in 42 patients with severe heart failure and 31 healthy volunteers to ascertain the rate at which epinephrine is released to plasma and to evaluate the contribution of extra-adrenal sources. The increase in arterial plasma epinephrine observed in the heart failure patients was explained principally by a 34% (P < 0.001) reduction in the whole body clearance rate of epinephrine from plasma. Regional venous sampling from the heart, lungs, and hepatomesenteric beds was performed in a subgroup of the study population, revealing a significant increase in the release rate of epinephrine to plasma from these organs in heart failure which accounted for 26% of the whole body plasma epinephrine appearance rate. To establish whether the cardiac epinephrine release was of neuronal origin, a physical (cycling) or mental (difficult mental arithmetic) stressor was applied as a sympathoexcitatory stimulus, given that a proportional release of norepinephrine and epinephrine could be expected if sympathetic nerves were the source. These interventions caused significant increases in the regional spillover of norepinephrine to plasma but not that of epinephrine. These findings suggest that nonadrenal tissues contribute significantly to the whole body epinephrine release rate in heart failure and that this may arise from a site other than sympathetic neurons. PMID:7631847

  5. The sympathetic nervous system through the ages: from Thomas Willis to resistant hypertension.

    PubMed

    Esler, Murray

    2011-07-01

    The 17th century London neuroanatomical school headed by Thomas Willis provided us with the first identifiable images of the sympathetic nervous system. Nineteenth century giants of European physiology (Bernard, Waller and Brown-Sequard) identified these as the 'pressor nerves'. Von Euler's demonstration that the sympathetic transmitter was noradrenaline brought the field into the modern era. The development of ganglion-blocking drugs by Paton, whose name this review commemorates, allowed comprehensive pharmacological antagonism of this system in patients. With the development of contemporary techniques for recording from human sympathetic nerves and quantifying rates of noradrenaline release, the sympathetic nervous system became accessible to clinical scientists investigating possible contributions to cardiovascular and other diseases. Sympathetic nervous system responses typically are regionally differentiated, with activation in one outflow sometimes accompanying no change or sympathetic inhibition in another. Regional sympathetic activity is best studied in humans by recording from postganglionic sympathetic efferents (multi-unit or single-fibre recording) and by isotope dilution-derived measurement of organ-specific noradrenaline release to plasma from sympathetic nerves (regional 'noradrenaline spillover'). With the application of these techniques, evidence has been assembled in the past three decades which indicates that sympathetic nervous system activation is crucial in the development of cardiovascular disorders, most notably heart failure and essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is mature in cardiac failure, with knowledge of cardiac neural pathophysiology having led to introduction of β-adrenergic blockers, an effective therapy. Perhaps we are now on the cusp of

  6. Sympathetic nervous system and inflammation: a conceptual view.

    PubMed

    Jänig, Wilfrid

    2014-05-01

    The peripheral sympathetic nervous system is organized into function-specific pathways that transmit the activity from the central nervous system to its target tissues. The transmission of the impulse activity in the sympathetic ganglia and to the effector tissues is target cell specific and guarantees that the centrally generated command is faithfully transmitted. This is the neurobiological basis of autonomic regulations in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to distinct central circuits in the spinal cord, lower and upper brain stem and hypothalamus. In addition to its conventional functions, the sympathetic nervous system is involved in protection of body tissues against challenges arising from the environment as well as from within the body. This function includes the modulation of inflammation, nociceptors and above all the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons and processes in the immune tissue are modulated by activity in these sympathetic neurons via adrenoceptors in the membranes of the immune cells (see Bellinger and Lorton, 2014). Are the primary and secondary lymphoid organs innervated by a functionally specific sympathetic pathway that is responsible for the modulation of the functioning of the immune tissue by the brain? Or is this modulation of immune functions a general function of the sympathetic nervous system independent of its specific functions? Which central circuits are involved in the neural regulation of the immune system in the context of neural regulation of body protection? What is the function of the sympatho-adrenal system, involving epinephrine, in the modulation of immune functions? PMID:24525016

  7. The sympathetic innervation of the heart: Important new insights.

    PubMed

    Coote, J H; Chauhan, R A

    2016-08-01

    Autonomic control of the heart has a significant influence over development of life threatening arrhythmias that can lead to sudden cardiac death. Sympathetic activity is known to be upregulated during these conditions and hence the sympathetic nerves present a target for treatment. However, a better understanding of the anatomy and physiology of cardiac sympathetic nerves is required for the progression of clinical interventions. This review explores the organization of the cardiac sympathetic nerves, from the preganglionic origin to the postganglionic innervations, and provides an overview of literature surrounding anti-arrhythmic therapies including thoracic sympathectomy and dorsal spinal cord stimulation. Several features of the innervation are clear. The cardiac nerves differentially supply the nodal and myocardial tissue of the heart and are dependent on activity generated in spinal neurones in the upper thoracic cord which project to synapse with ganglion cells in the stellate complex on each side. Networks of spinal interneurones determine the pattern of activity. Groups of spinal neurones selectively target specific regions of the heart but whether they exhibit a functional selectivity has still to be elucidated. Electrical or ischemic signals can lead to remodeling of nerves in the heart or ganglia. Surgical and electrical methods are proving to be clinically beneficial in reducing atrial and ventricular arrhythmias, heart failure and severe cardiac pain. This is a rapidly developing area and we need more basic understanding of how these methods work to ensure safety and reduction of side effects. PMID:27568995

  8. Bioluminescence imaging of mitochondrial Ca2+ dynamics in soma and neurites of individual adult mouse sympathetic neurons

    PubMed Central

    Núñez, Lucía; Senovilla, Laura; Sanz-Blasco, Sara; Chamero, Pablo; Alonso, María T; Villalobos, Carlos; García-Sancho, Javier

    2007-01-01

    Changes in the cytosolic Ca2+ concentration ([Ca2+]c) are essential for triggering neurotransmitter release from presynaptic nerve terminals. Calcium-induced Ca2+ release (CICR) from the endoplasmic reticulum (ER) may amplify the [Ca2+]c signals and facilitate neurotransmitter release in sympathetic neurons. In adrenal chromaffin cells, functional triads are formed by voltage-operated Ca2+ channels (VOCCs), CICR sites and mitochondria. In fact, mitochondria take up most of the Ca2+ load entering the cells and are essential for shaping [Ca2+]c signals and exocytosis. Here we have investigated the existence of such functional triads in sympathetic neurons. The mitochondrial Ca2+ concentration ([Ca2+]m) in soma and neurites of individual mouse superior cervical ganglion (SCG) neurons was monitored by bioluminescence imaging of targeted aequorins. In soma, Ca2+ entry through VOCCs evoked rapid, near millimolar [Ca2+]m increases in a subpopulation of mitochondria containing about 40% of the aequorin. Caffeine evoked a similar [Ca2+]m increase in a mitochondrial pool containing about 30% of the aequorin and overlapping with the VOCC-sensitive pool. These observations suggest the existence of functional triads similar to the ones described in chromaffin cells. In neurites, mitochondria were able to buffer [Ca2+]c increases resulting from activation of VOCCs but not those mediated by caffeine-induced Ca2+ release from the ER. The weaker Ca2+ buffering by mitochondria in neurites could contribute to facilitate Ca2+-induced exocytosis at the presynaptic sites. PMID:17234693

  9. The Sympathetic Release Test: A Test Used to Assess Thermoregulation and Autonomic Control of Blood Flow

    ERIC Educational Resources Information Center

    Tansey, E. A.; Roe, S. M.; Johnson, C. J.

    2014-01-01

    When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the…

  10. Do changes in the coupling between respiratory and sympathetic activities contribute to neurogenic hypertension?

    PubMed

    Zoccal, Daniel B; Paton, Julian F R; Machado, Benedito H

    2009-12-01

    1. It is well known that respiration markedly modulates the sympathetic nervous system. Interactions between pontine and medullary neurons involved in the control of sympathetic and respiratory functions are the main mechanism underlying the respiratory related oscillations in sympathetic nerve activity. 2. Recently, in rats treated with chronic intermittent hypoxia, we demonstrated that alterations in respiratory pattern may drive increased sympathetic outflow and hence the development of systemic hypertension. These experiments, performed in the in situ working heart-brain stem preparation, raise the possibility that enhanced central coupling between respiratory and sympathetic activities could be a potential mechanism underpinning the development and/or the maintenance of neurogenic hypertension. 3. In the present review, we discuss the neural basis of the enhanced entrainment between respiratory and sympathetic neurons in the brain stem that can be induced by chronic intermittent hypoxia and the possible implications of these mechanisms in the genesis of sympathetic overactivity and, consequently, hypertension. PMID:19413588

  11. Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation

    PubMed Central

    Borden, Philip; Houtz, Jessica; Leach, Steven D.; Kuruvilla, Rejji

    2013-01-01

    Summary Sympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in de-innervated animals. Furthermore, in neuron-islet co-cultures, sympathetic neurons promoted islet cell migration in a β-adrenergic dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves, and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders. PMID:23850289

  12. Sympathetic skin response in acute sensory ataxic neuropathy.

    PubMed

    Arunodaya, G R; Taly, A B; Swamy, H S

    1995-05-01

    Sympathetic skin response (SSR) is a recently described objective method of studying sudomotor sympathetic nerve function and has been studied in a variety of peripheral neuropathies. We report SSR changes in nine patients with acute sensory ataxic neuropathy (ASAN). All had severe sensory and mild motor nerve conduction abnormalities; five had dysautonomia. SSR, elicited by electric shock and cough stimuli, was absent in three patients. Latency was normal in all when SSR was present. Two patients had SSR amplitude of 0.2 mV or less. Absence of SSR did not correlate with dysautonomia, absence of sensory nerve action potential or motor nerve conduction abnormalities. Follow up SSR studies revealed return of absent SSR in one patient over a period of 3 months, despite persistence of ataxia. To our knowledge, this is the first report of SSR changes in ASAN.

  13. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  14. Renal Sympathetic Denervation: Hibernation or Resurrection?

    PubMed

    Papademetriou, Vasilios; Doumas, Michael; Tsioufis, Costas

    2016-01-01

    The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research. PMID:27287994

  15. Impaired sympathetic vascular regulation in humans after acute dynamic exercise.

    PubMed Central

    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. Images Figure 7 PMID:8866370

  16. 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.

  17. A Sympathetic Neuron Autonomous Role for Egr3-Mediated Gene Regulation in Dendrite Morphogenesis and Target Tissue Innervation

    PubMed Central

    Quach, David H.; Oliveira-Fernandes, Michelle; Gruner, Katherine A.; Tourtellotte, Warren G.

    2013-01-01

    Egr3 is a nerve growth factor (NGF)-induced transcriptional regulator that is essential for normal sympathetic nervous system development. Mice lacking Egr3 in the germline have sympathetic target tissue innervation abnormalities and physiologic sympathetic dysfunction similar to humans with dysautonomia. However, since Egr3 is widely expressed and has pleiotropic function, it has not been clear whether it has a role within sympathetic neurons and if so, what target genes it regulates to facilitate target tissue innervation. Here, we show that Egr3 expression within sympathetic neurons is required for their normal innervation since isolated sympathetic neurons lacking Egr3 have neurite outgrowth abnormalities when treated with NGF and mice with sympathetic neuron-restricted Egr3 ablation have target tissue innervation abnormalities similar to mice lacking Egr3 in all tissues. Microarray analysis performed on sympathetic neurons identified many target genes deregulated in the absence of Egr3, with some of the most significantly deregulated genes having roles in axonogenesis, dendritogenesis, and axon guidance. Using a novel genetic technique to visualize axons and dendrites in a subpopulation of randomly labeled sympathetic neurons, we found that Egr3 has an essential role in regulating sympathetic neuron dendrite morphology and terminal axon branching, but not in regulating sympathetic axon guidance to their targets. Together, these results indicate that Egr3 has a sympathetic neuron autonomous role in sympathetic nervous system development that involves modulating downstream target genes affecting the outgrowth and branching of sympathetic neuron dendrites and axons. PMID:23467373

  18. Surgical anatomy of the retroperitoneal spaces, Part IV: retroperitoneal nerves.

    PubMed

    Mirilas, Petros; Skandalakis, John E

    2010-03-01

    We present surgicoanatomical topographic relations of nerves and plexuses in the retroperitoneal space: 1) six named parietal nerves, branches of the lumbar plexus: iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, obturator, femoral. 2) The sacral plexus is formed by the lumbosacral trunk, ventral rami of S1-S3, and part of S4; the remainder of S4 joining the coccygeal plexus. From this plexus originate the superior gluteal nerve, which passes backward through the greater sciatic foramen above the piriformis muscle; the inferior gluteal nerve also courses through the greater sciatic foramen, but below the piriformis; 3) sympathetic trunks: right and left lumbar sympathetic trunks, which comprise four interconnected ganglia, and the pelvic chains; 4) greater, lesser, and least thoracic splanchnic nerves (sympathetic), which pass the diaphragm and join celiac ganglia; 5) four lumbar splanchnic nerves (sympathetic), which arise from lumbar sympathetic ganglia; 6) pelvic splanchnic nerves (nervi erigentes), providing parasympathetic innervation to the descending colon and pelvic splanchna; and 7) autonomic (prevertebral) plexuses, formed by the vagus nerves, splanchnic nerves, and ganglia (celiac, superior mesenteric, aorticorenal). They include sympathetic, parasympathetic, and sensory (mainly pain) fibers. The autonomic plexuses comprise named parts: aortic, superior mesenteric, inferior mesenteric, superior hypogastric, and inferior hypogastric (hypogastric nerves).

  19. Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex.

    PubMed

    Ichinose, Tomoko K; Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2012-09-01

    Previously we have shown that adenosine operating via the A(1) receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A(1) receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats (n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT(3) receptor agonist phenylbiguanide, PBG, 1-8 μg/kg) before and after selective stimulation of NTS A(1) adenosine receptors [microinjections of N(6)-cyclopentyl adenosine (CPA), 0.033-330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control (n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-(p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) (n = 9) did not affect the reflex responses. We conclude that activation of NTS A(1) adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A(1) adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes

  20. Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

    PubMed Central

    2012-01-01

    Background Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams) with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs) into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established. Methods In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams. Results Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic) dams. In pups exposed to nerve growth factor (NGF) in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels. Conclusions Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process. PMID:23137120

  1. Bursting into space: alterations of sympathetic control by space travel

    NASA Technical Reports Server (NTRS)

    Eckberg, D. L.

    2003-01-01

    AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

  2. Effects of CH-19 sweet, a non-pungent cultivar of red pepper, in decreasing the body weight and suppressing body fat accumulation by sympathetic nerve activation in humans.

    PubMed

    Kawabata, Fuminori; Inoue, Naohiko; Yazawa, Susumu; Kawada, Teruo; Inoue, Kazuo; Fushiki, Tohru

    2006-12-01

    'CH-19 Sweet' is a non-pungent red pepper and enhances the energy expenditure in humans in like manner to the pungent red pepper. We investigated in this study the effects of a repeated intake of CH-19 Sweet for two weeks on the body weight and body fat in humans. Changes in the autonomic nervous activity after ingesting CH-19 Sweet were also measured by a power spectral analysis. We established a new protocol which allows the precise detection of weight change in humans by using fewer subjects. These methods were used to show that the repeated intake of CH-19 Sweet reduced the body weight and suppressed body fat accumulation. Furthermore, the body weight loss due to the repeated intake of CH-19 Sweet was significantly correlated with the sympathetic nervous response after its ingestion. We propose that the repeated intake of CH-19 Sweet reduced the body weight and suppressed body fat accumulation by sympathetic nervous activation in humans.

  3. Selective response of rat peripheral sympathetic nervous system to various stimuli

    PubMed Central

    Ulus, I. H.; Wurtman, R. J.

    1979-01-01

    1. We utilized the induction of tyrosine hydroxylase, a catecholamine-synthesizing enzyme, in sympathetic ganglia and adrenal medullae to explore the central and peripheral mechanisms through which choline, various environmental stresses, and drugs that alter blood pressure or central neurotransmission affect various portions of the sympathetic nervous system. Animals received each treatment chronically, and enzyme activity was measured in the superior cervical, stellate, and coeliac ganglia and in the adrenal medullae. 2. Choline administration increased tyrosine hydroxylase activity in all four tissues, probably by increasing the release of acetylcholine from preganglionic sympathetic neurones that synapse on catecholamine-producing ganglion and chromaffin cells; carbachol and nicotine had similar effects. 3. Insulin enhanced tyrosine hydroxylase activity primarily in the coeliac ganglion and the adrenal medullae, but not in the superior cervical ganglia. 4. Reserpine and phenoxybenzamine increased the activity of the enzyme in all four tissues. 5. Prolonged exposure to a cold environment increased enzyme activity in all four tissues, but especially in the stellate and coeliac ganglia; forced swimming affected tyrosine hydroxylase only in these two ganglia. 6. Several drugs known to modify central neurotransmission were found to increase tyrosine hydroxylase activity in some portions of the sympathetic nervous system but not in others. 5,7-Dihydroxytryptamine, which destroys terminals of serotoninergic neurones, enhanced enzyme activity in all four tissues, but primarily in the coeliac ganglion and adrenal medullae. ET-495 (a dopaminergic agonist), D-amphetamine, and morphine induced tyrosine hydroxylase activity in the adrenal medullae and the coeliac ganglion, but not in the superior cervical ganglia. Oxotremorine, a centrally acting muscarinic agonist, increased tyrosine hydroxylase activity only in the adrenal medullae; its effect was not blocked by

  4. Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

    PubMed Central

    Turcu, Adina F.; Auchus, Richard J.

    2015-01-01

    Synopsis Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids, glucocorticoids and adrenal androgens occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive enzymatic defects in cortisol biosynthesis. 21-hydroxylase (21OHD) deficiency accounts for over 90% of CAH cases and when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. This review discusses in detail the epidemiology, genetics, diagnostic, clinical aspects and management of 21OHD. PMID:26038201

  5. How Is Adrenal Surgery Performed?

    MedlinePlus

    HOME ADRENAL GLANDS Background Where are the adrenal glands? What do the adrenal glands do? Is this adrenal tumor a genetic problem? Primary hyperaldosteronism (aldosterone-producing tumor) What is primary hyperaldosteronism? Signs ...

  6. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

    SciTech Connect

    Stanton, M.S.; Tuli, M.M.; Radtke, N.L.; Heger, J.J.; Miles, W.M.; Mock, B.H.; Burt, R.W.; Wellman, H.N.; Zipes, D.P. )

    1989-11-15

    Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

  7. Intracranial distribution of the sympathetic system in mice: DiI tracing and immunocytochemical labeling

    NASA Technical Reports Server (NTRS)

    Maklad, A.; Quinn, T.; Fritzsch, B.

    2001-01-01

    The intracranial distribution of the cephalic branches of the superior cervical ganglion (scg) was studied in mice using indocarbocyanine dye (DiI) anterograde tracing. Two main branches were traced from the scg. The first branch joined the nerve of the pterygoid canal (the vidian nerve), npc, from which several intracranial sympathetic branches passed to the branches of the trigeminal nerve (tgn), abducent nerve (abn), trochlear nerve (trn), and oculomotor nerve (ocn). Most of the second branch joined the abn, from which sympathetic fibers dispersed in the distal region of the trigeminal ganglion (tgg) to form a plexus close to the ganglion's branches. Branches from this plexus joined the branches of the tgn, trn, and ocn. Several minor branches arising from the second branch of the scg were also observed. One formed a sympathetic plexus around the internal carotid artery (ica); a second formed a sympathetic plexus in the proximal region of tgg, close to its root; and a third branch coursed laterally to reach the ear by passing along the greater petrosal nerve (gpn). All of the intracranial trajectories traced from scg were found to be catecholaminergic, and likely sympathetic, using tyrosine hydroxylase (TH) immunocytochemistry.

  8. 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.

  9. Laparoscopic Adrenal Gland Removal

    MedlinePlus

    ... adrenal tumors that appear malignant. What are the Advantages of Laparoscopic Adrenal Gland Removal? In the past, ... of procedure and the patients overall condition. Common advantages are: Less postoperative pain Shorter hospital stay Quicker ...

  10. Adrenal Gland Disorders

    MedlinePlus

    The adrenal glands are small glands located on top of each kidney. They produce hormones that you can't live ... stress and has many other important functions. With adrenal gland disorders, your glands make too much or not ...

  11. Adrenal Gland Cancer

    MedlinePlus

    ... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

  12. Direct Evidences for Sympathetic Hyperactivity and Baroreflex Impairment in Tako Tsubo Cardiopathy

    PubMed Central

    Delmas, Clement; Lairez, Olivier; Lambert, Elisabeth; Lambert, Gavin; Labrunee, Marc; Guiraud, Thibaut; Esler, Murray; Galinier, Michel; Senard, Jean Michel; Pathak, Atul

    2014-01-01

    Background The exact pathophysiology of Tako-Tsubo cardiomyopathy (TTC) remains unknown but a role for sympathetic hyperactivity has been suggested. Up to now, no direct evidence of sympathetic nerve hyperactivity has been established nor involvement of sympathetic baroreflex identified. The aim of our study was to determine, by direct sympathetic nerve activity (SNS) recording if sympathetic nervous system activity is increased and spontaneous baroreflex control of sympathetic activity reduced in patients with TTC. Methods We included 13 patients who presented with TTC and compared their SNS activity and spontaneous baroreflex control of sympathetic activity with that of 13 control patients with acutely decompensated chronic heart failure. SNS activity was evaluated by microneurography, a technique assessing muscle sympathetic nerve activity (MSNA). Spontaneous baroreflex control of sympathetic activity was evaluated as the absolute value of the slope of the regression line representing the relationship between spontaneous diastolic blood pressure values and concomitant SNS activity. Control patients were matched for age, sex, left ventricular ejection fraction and creatinine clearance. Results The mean age of the patients with TTC was 80 years, all patients were women. There were no significant differences between the two groups of patients for blood pressure, heart rate or oxygen saturation level. TTC patients presented a significant increase in sympathetic nerve activity (MSNA median 63.3 bursts/min [interquartile range 61.3 to 66.0] vs median 55.7 bursts/min [interquartile range 51.0 to 61.7]; p = 0.0089) and a decrease in spontaneous baroreflex control of sympathetic activity compared to matched control patients (spontaneous baroreflex control of sympathetic activity median 0.7%burst/mmHg [interquartile range 0.4 to 1.9] vs median 2.4%burst/mmHg [interquartile range 1.8 to 2.9]; p = 0.005). Conclusions We report for the first time, through direct

  13. Electrical excitability of cultured adrenal chromaffin cells.

    PubMed Central

    Biales, B; Dichter, M; Tischler, A

    1976-01-01

    1. Adult human and gerbil adrenal medullary cells were maintained in dissociated cell culture and studied by micro-electrode penetration. 2. In the best recordings, chromaffin cell transmembrane potentials exceeded -50mV. 3. Chromaffin cells were capable of generating all-or-nothing over-shooting action potentials, similar to those generated by sympathetic neurones. 4. The action potentials were blocked by tetrodotoxin (TTX, 10(-6)g/ml.) but were not blocked by removal of Ca or by CoCl2 (10 mM). We conclude that the action potentials are probably generated by a Na mechanism. 5. Chromaffin cells are depolarized by the iontophoretic application of acetylcholine (ACh). This depolarization was accompanied by an increased membrane conductance and could trigger action potentials. 6. Action potentials were also found in cells in fresh slices of gerbil adrenal medullae. Images Plate 1 PMID:1034699

  14. Interaction of Xylamine with peripheral sympathetic neurons

    SciTech Connect

    Ransom, R.W.; Waggaman, L.A.; Cho, A.K.

    1985-09-30

    Xylamine (XYL) administered to intact rats caused a 70-80% reduction in norepinephrine (NE) uptake by the vas deferens but had little or no effect on NE content in that tissue. The vas deferens accumulates /sup 3/H-XYL in vitro by a desmethylimipramine (DMI)-sensitive mechanism. Vasa deferentia from 6-hydroxydopamine (60HDA) pretreated animals exhibited a 80% reduction in both NE content and XYL uptake activity. These results indicate that XYL is taken up by sympathetic nerve terminals and can reduce NE uptake activity without depleting terminals of neurotransmitter. 9 references, 4 tables.

  15. Adrenal imaging (Part 2): Medullary and secondary adrenal lesions

    PubMed Central

    Dhamija, Ekta; Panda, Ananya; Das, Chandan J.; Gupta, A. K.

    2015-01-01

    Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations. PMID:25593821

  16. Ontogeny of cardiac sympathetic innervation and its implications for cardiac disease.

    PubMed

    Vincentz, Joshua W; Rubart, Michael; Firulli, Anthony B

    2012-08-01

    The vertebrate heart is innervated by the sympathetic and parasympathetic components of the peripheral autonomic nervous system, which regulates its contractile rate and force. Understanding the mechanisms that control sympathetic neuronal growth, differentiation, and innervation of the heart may provide insight into the etiology of cardiac arrhythmogenesis. This review provides an overview of the cell signaling pathways and transcriptional effectors that regulate both the noradrenergic gene program during sympathetic neurogenesis and regional nerve density during cardiac innervation. Recent studies exploring transcriptional regulation of the bHLH transcription factor Hand1 in developing sympathetic neurons are explored, and how the Hand1 sympathetic neuron-specific cis-regulatory element may be used further to assess the contribution of altered sympathetic innervation to human cardiac disease is discussed.

  17. Disorders of adrenal development.

    PubMed

    Ferraz-de-Souza, Bruno; Achermann, John C

    2008-01-01

    Human adrenal development is a complex and relatively poorly understood process. However, significant insight into some of the mechanisms regulating adrenal development and function is being obtained through the analysis of individuals and families with adrenal hypoplasia. Adrenal hypoplasia can occur: (1) secondary to defects in pituitary adrenocorticotropin (ACTH) synthesis, processing and release (secondary adrenal hypoplasia; e.g. HESX1, LHX4, SOX3, TPIT, pituitary POMC, PC1); (2) as part of several ACTH resistance syndromes (e.g. MC2R/ACTHR, MRAP, Alacrima, Achalasia, Addison disease), or as (3) a primary defect in the development of the adrenal gland itself (primary adrenal hypoplasia; e.g. DAX1/NR0B1 - dosage-sensitive sex reversal, adrenal hypoplasia congenita critical region on the X chromosome 1). Indeed, the X-linked form of primary adrenal hypoplasia due to deletions or mutations in the orphan nuclear receptor DAX1 occurs in around half of male infants presenting with a salt-losing adrenal crisis, where no obvious steroidogenic defect (e.g. 21-hydroxylase deficiency), metabolic abnormality (e.g. neonatal adrenoleukodystrophy) or physical cause (e.g. adrenal haemorrhage) is found. Establishing the underlying basis of adrenal failure can have important implications for investigating associated features, the likely long-term approach to treatment, and for counselling families about the risk of other children being affected.

  18. Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial.

    PubMed

    Verloop, Willemien L; Beeftink, Martine M A; Nap, Alex; Bots, Michiel L; Velthuis, Birgitta K; Appelman, Yolande E; Cramer, Maarten-Jan; Agema, Willem R P; Scholtens, Asbjorn M; Doevendans, Pieter A; Allaart, Cor P; Voskuil, Michiel

    2013-12-01

    Aim Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or to maintain medical treatment alone (n = 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed. Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881.

  19. Stimulation of NTS A1 adenosine receptors differentially resets baroreflex control of regional sympathetic outputs.

    PubMed

    Scislo, Tadeusz J; Ichinose, Tomoko K; O'Leary, Donal S

    2008-01-01

    Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal > renal >/= lumbar) evoked by stimulation of A(1) adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A(1) receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activity. In urethane-chloralose-anesthetized male Sprague-Dawley rats (n = 65) we compared baroreflex-response curves (iv nitroprusside and phenylephrine) evoked before and after bilateral microinjections into the NTS of A(1) adenosine receptor agonist (N(6)-cyclopentyladenosine, CPA; 0.033-330 pmol/50 nl). CPA evoked typical dose-dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA, and LSNA toward higher mean arterial pressure (MAP) in a dose-dependent manner; the maximal shifts were 52.6 +/- 2.8, 48.0 +/- 3.6, and 56.8 +/- 6.7 mmHg for pre-ASNA, RSNA, and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting because they were two to three times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upward: the maximal increases of upper and lower plateaus were 41.8 +/- 16.4% and 45.3 +/- 8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0 +/- 0.6 vs. 4.9 +/- 1.3), decreased for RSNA (4.1 +/- 0.6 vs. 2.3 +/- 0.3), and remained unaltered for LSNA (2.1 +/- 0.2 vs. 2.0 +/- 0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A(1) adenosine receptors differentially inhibits

  20. Pial artery diameter and blood flow velocity during sympathetic stimulation in cats.

    PubMed

    Busija, D W; Marcus, M L; Heistad, D D

    1982-09-01

    The effects of sympathetic stimulation on the cerebral circulation in cats are in dispute. One unexplained observation is that sympathetic nerve stimulation constricts pial arteries but does not decrease cerebral blood flow (CBF). To reconcile these findings, we studied effects of sympathetic nerves on cerebral vessels using a new method that permits virtually continuous measurement of pial artery diameter and blood flow velocity, and calculation of change in CBF. Change in CBF was calculated as the product of cross-sectional area (CSA) and blood flow velocity in a large pial artery. Pial artery diameter was measured with the cranial window method and CSA was calculated (pi r2). Blood flow velocity was measured with a pulsed Doppler velocity meter. In 11 cats, CBF was measured duringg the control period and during electrical stimulation of sympathetic nerves. During stimulation, arterial diameter decreased 6 +/- 1%, but CBF did not change because velocity increased 19 +/- 5%. We also measured CBF with microspheres during control and after 60 s of sympathetic stimulation. Cerebral blood flow was 28 +/- 3 ml/min/100 g during control and 26 +/- 3 ml/min/100 g after 60 s of sympathetic stimulation (n = 5). It is likely that the increase in velocity durin sympathetic stimulation was due to compensatory dilatation of downstream arteries.

  1. Remodelling sympathetic innervation in rat pancreatic islets ontogeny

    PubMed Central

    Cabrera-Vásquez, Siraam; Navarro-Tableros, Víctor; Sánchez-Soto, Carmen; Gutiérrez-Ospina, Gabriel; Hiriart, Marcia

    2009-01-01

    Background Pancreatic islets are not fully developed at birth and it is not clear how they are vascularised and innervated. Nerve Growth Factor (NGF) is required to guide sympathetic neurons that innervate peripheral organs and also in cardiovascular system and ovary angiogenesis. Pancreatic beta cells of a transgenic mouse that over-expressed NGF in attracts sympathetic hyper-innervation towards them. Moreover, we have previously demonstrated that adult beta cells synthesize and secrete NGF; however, we do not know how is NGF secreted during development, nor if it might be trophic for sympathetic innervation and survival in the pancreas. We analyzed sympathetic innervation and vasculature development in rat pancreatic islets at different developmental stages; foetal (F19), early postnatal (P1), weaning period (P20) and adults. We temporarily correlated these events to NGF secretion by islet cells. Results Sympathetic fibres reached pancreatic islets in the early postnatal period, apparently following blood vessels. The maximal number of sympathetic fibres (TH immunopositive) in the periphery of the islets was observed at P20, and then fibres entered the islets and reached the core where beta cells are mainly located. The number of fibres decreased from that stage to adulthood. At all stages studied, islet cells secreted NGF and also expressed the high affinity receptor TrkA. Foetal and neonatal isolated islet cells secreted more NGF than adults. TrkA receptors were expressed at all stages in pancreatic sympathetic fibres and blood vessels. These last structures were NGF–immunoreactive only at early stages (foetal and P0). Conclusion The results suggest that NGF signalling play an important role in the guidance of blood vessels and sympathetic fibres toward the islets during foetal and neonatal stages and could also preserve innervation at later stages of life. PMID:19534767

  2. Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

    PubMed Central

    Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

    2014-01-01

    Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic

  3. Role of adrenal imaging in surgical management

    SciTech Connect

    Lamki, L.M.; Haynie, T.P. )

    1990-03-01

    Adrenal imaging using radiopharmaceuticals is a functional test that can contribute significantly to surgical management and follow-up of patients with either benign or malignant conditions of the adrenal cortex and medulla. Imaging of the cortex is achieved by iodine-131-labeled iodomethyl nor-cholesterol (NP-59), while adrenal medulla imaging can be successfully accomplished by 131I-metaiodobenzylguanidine (MIBG), which localizes in the adrenergic nerve terminal with norepinephrine. Both tests carry high sensitivity and specificity for functional tumors and hyperplasia, and often better than CT scanning. This article reviews the current status and clinical utility of nuclear imaging of the adrenal cortex in congenital hyperplasia, low renin hypertension and aldosteronism, and Cushing's syndrome. Adrenal medulla imaging is reviewed in light of our experience at the University of Texas M.D. Anderson Cancer Center in pheochromocytoma, neuroblastoma, and other neuroectodermal tumors. Investigation of {sup 131}I-MIBG therapy of metastatic tumors of neuroectodermal origin potentially offers a means of at least controlling symptoms of hormonal secretion in these patients. 40 references.

  4. Hemorrhagic adrenal cyst.

    PubMed

    Cunningham, M D

    1993-05-01

    Adrenal cysts are uncommon. They may be fatal if they hemorrhage and are not rapidly diagnosed. Most adrenal cysts are small and asymptomatic. When they are symptomatic, it is usually because the cyst has enlarged, causing flank discomfort, gastrointestinal complaints, and hemorrhage. Occasionally, a palpable mass may be found. It is thought that hemorrhage occurs secondary to trauma or some toxic or infectious process. The author describes a case in which a previously healthy man had a sudden hemorrhage within a benign adrenal cyst with infarction of the kidney. A discussion of adrenal cysts follows.

  5. Congenital Adrenal Hyperplasia

    PubMed Central

    Speiser, Phyllis W.

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management. PMID:26339484

  6. Sympathetic adaptations to one-legged training

    NASA Technical Reports Server (NTRS)

    Ray, C. A.

    1999-01-01

    The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.

  7. Sympathetic adaptations to one-legged training.

    PubMed

    Ray, C A

    1999-05-01

    The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training. PMID:10233121

  8. Central chemoreceptors and sympathetic vasomotor outflow

    PubMed Central

    Moreira, Thiago S; Takakura, Ana C; Colombari, Eduardo; Guyenet, Patrice G

    2006-01-01

    The present study explores how elevations in brain PCO2 increase the sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVLM) were recorded in anaesthetized sino-aortic denervated and vagotomized rats. Hypercapnia (end-expiratory CO2 from 5% to 10%) increased SND (97 ± 6%) and the activity of RVLM neurons (67 ± 4%). Injection of kynurenic acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not change the effect of CO2 on SND. Bilateral injection of Kyn or muscimol into the rostral ventral respiratory group (rVRG-pre-Bötzinger region, also called CVLM) eliminated PND while increasing the stimulatory effect of CO2 on SND. Muscimol injection into commissural part of the solitary tract nucleus (commNTS) had no effect on PND or SND activation by CO2. As expected, injection of Kyn into RVLM or muscimol into commNTS virtually blocked the effect of carotid body stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO2 increases SND by activating RVLM sympathoexcitatory neurons. The relevant central chemoreceptors are probably located within or close to RVLM and not in the NTS or in the rVRG-pre-Bötzinger/CVLM region. RVLM sympathoexcitatory neurons may be intrinsically pH-sensitive and/or receive excitatory synaptic inputs from RTN chemoreceptors. Activation of the central respiratory network reduces the overall sympathetic response to CO2, presumably by activating barosensitive CVLM neurons and inhibiting RTN chemoreceptors. PMID:16901945

  9. Sympathetic Neural and Hemodynamic Responses During Cold Pressor Test in Elderly Blacks and Whites.

    PubMed

    Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Edwards, Jeffrey G; Hendrix, Joseph M; Adams-Huet, Beverley; Vongpatanasin, Wanpen; Levine, Benjamin D; Fu, Qi

    2016-05-01

    The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Because blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate, cardiac output, and muscle sympathetic nerve activity were measured during supine baseline, 2-minute CPT, and 3-minute recovery in 47 elderly (68 ± 7 [SD] years) volunteers (12 blacks and 35 whites). Baseline BP, heart rate, cardiac output, or muscle sympathetic nerve activity did not differ between races. Systolic and diastolic BP and heart rate increased during CPT (all P<0.001) with no racial differences (all P > 0.05). Cardiac output increased during CPT and ≤ 30 s of recovery in both groups, but was lower in blacks than whites. Muscle sympathetic nerve activity increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, whereas the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (Δ) in diastolic BP was correlated with Δ total activity at 1 minute into CPT in both blacks (r=0.78,P=0.003) and whites (r=0.43,P=0.009), whereas the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (eg, cardiac output) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), or enhanced nonadrenergically mediated vasoconstriction in elderly blacks. PMID:27021009

  10. Spironolactone prevents chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients.

    PubMed

    Raheja, Prafull; Price, Angela; Wang, Zhongyun; Arbique, Debbie; Adams-Huet, Beverley; Auchus, Richard J; Vongpatanasin, Wanpen

    2012-08-01

    Recent studies from our laboratory indicate that chlorthalidone triggers persistent activation of the sympathetic nervous system and promotes insulin resistance in hypertensive patients, independent of serum potassium. Mechanisms underlying these adverse effects of chlorthalidone remain unknown, but increasing evidence in rodents suggests the role of angiotensin and aldosterone excess in inducing both sympathetic overactivity and insulin resistance. Accordingly, we conducted studies in 17 subjects with untreated stage 1 hypertension, measuring sympathetic nerve activity at baseline and after 12 weeks of chlorthalidone alone (25 mg/d), chlorthalidone plus spironolactone, and chlorthalidone plus irbesartan, using randomized crossover design. We found that chlorthalidone alone decreased 24-hour ambulatory blood pressure from 135±3/84±2 to 124±2/78±2 mm Hg and significantly increased sympathetic nerve activity from baseline (from 41±3 versus 49±4 bursts per minute; P<0.01). The addition of spironolactone to chlorthalidone returned sympathetic nerve activity value to baseline (42±3 bursts per minute; P>0.05), whereas the addition of irbesartan failed to alter the sympathetic nerve activity response to chlorthalidone in the same subjects (52±2 bursts per minute; P<0.01) despite a similar reduction in ambulatory blood pressure (121±2/75±2 and 121±2/75±2 mm Hg, respectively). Chlorthalidone alone also increased indices of insulin resistance, which was not observed when used in combination with spironolactone. In conclusion, our study demonstrates beneficial effects of spironolactone in attenuating both chlorthalidone-induced sympathetic activation and insulin resistance in humans, independent of blood pressure reduction. Because sympathetic overactivity and insulin resistance contribute to the poor prognosis in patients with cardiovascular disease, combination therapy of chlorthalidone with mineralocorticoid receptor antagonists may constitute a preferable

  11. Microneurographic evidence of sudden sympathetic withdrawal in carotid sinus syncope; treatment with ergotamine

    NASA Technical Reports Server (NTRS)

    Costa, F.; Biaggioni, I.

    1994-01-01

    A proportion of patients with carotid sinus syncope (CSS) remain symptomatic even after pacemaker implantation because of persistence of a vasodepressor component. We report a patient with CSS whose syncopal episodes could be reproduced by carotid sinus massage and were due to profound hypotension associated with sudden sympathetic withdrawal, based on direct measurements of sympathetic nerve traffic. A double-blind trial with inhaled ergotamine provided significant symptomatic relief.

  12. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.

    PubMed

    Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-11-01

    We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

  13. Highly localized interactions between sensory neurons and sprouting sympathetic fibers observed in a transgenic tyrosine hydroxylase reporter mouse

    PubMed Central

    2011-01-01

    Background Sprouting of sympathetic fibers into sensory ganglia occurs in many preclinical pain models, providing a possible anatomical substrate for sympathetically enhanced pain. However, the functional consequences of this sprouting have been controversial. We used a transgenic mouse in which sympathetic fibers expressed green fluorescent protein, observable in live tissue. Medium and large diameter lumbar sensory neurons with and without nearby sympathetic fibers were recorded in whole ganglion preparations using microelectrodes. Results After spinal nerve ligation, sympathetic sprouting was extensive by 3 days. Abnormal spontaneous activity increased to 15% and rheobase was reduced. Spontaneously active cells had Aαβ conduction velocities but were clustered near the medium/large cell boundary. Neurons with sympathetic basket formations had a dramatically higher incidence of spontaneous activity (71%) and had lower rheobase than cells with no sympathetic fibers nearby. Cells with lower density nearby fibers had intermediate phenotypes. Immunohistochemistry of sectioned ganglia showed that cells surrounded by sympathetic fibers were enriched in nociceptive markers TrkA, substance P, or CGRP. Spontaneous activity began before sympathetic sprouting was observed, but blocking sympathetic sprouting on day 3 by cutting the dorsal ramus in addition to the ventral ramus of the spinal nerve greatly reduced abnormal spontaneous activity. Conclusions The data suggest that early sympathetic sprouting into the sensory ganglia may have highly localized, excitatory effects. Quantitatively, neurons with sympathetic basket formations may account for more than half of the observed spontaneous activity, despite being relatively rare. Spontaneous activity in sensory neurons and sympathetic sprouting may be mutually re-enforcing. PMID:21794129

  14. Relationship between spontaneous sympathetic baroreflex sensitivity and cardiac baroreflex sensitivity in healthy young individuals.

    PubMed

    Taylor, Chloe E; Witter, Trevor; El Sayed, Khadigeh; Hissen, Sarah L; Johnson, Aaron W; Macefield, Vaughan G

    2015-11-01

    Low baroreflex sensitivity (BRS) is associated with elevated cardiovascular risk. However, the evidence is based primarily on measurements of cardiac BRS. It cannot be assumed that cardiac or sympathetic BRS alone represent a true reflection of baroreflex control of blood pressure. The aim of this study was to examine the relationship between spontaneous sympathetic and cardiac BRS in healthy, young individuals. Continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made under resting conditions in 50 healthy individuals (18-28 years). 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 by plotting R-R interval against systolic pressure using the sequence method. Significant sympathetic BRSinc and cardiac BRS slopes were obtained for 42 participants. A significant positive correlation was found between sympathetic BRSinc and cardiac BRS (r = 0.31, P = 0.049). Among this group, significant sympathetic baroreflex slopes were obtained for 39 participants when plotting total MSNA against diastolic pressure. In this subset, a significant positive correlation was observed between sympathetic BRStotal and cardiac BRS (r = 0.40, P = 0.012). When males and females were assessed separately, these modest relationships only remained significant in females. Analysis by gender revealed correlations in the females between sympathetic BRSinc and cardiac BRS (r = 0.49, P = 0.062), and between sympathetic BRStotal and cardiac BRS (r = 0.57, P = 0.025). These findings suggest that gender interactions exist in baroreflex control of blood pressure, and that cardiac BRS is not appropriate for estimating overall baroreflex function in healthy, young populations. This relationship warrants investigation in aging and clinical populations. PMID:26564059

  15. Relationship between spontaneous sympathetic baroreflex sensitivity and cardiac baroreflex sensitivity in healthy young individuals

    PubMed Central

    Taylor, Chloe E; Witter, Trevor; El Sayed, Khadigeh; Hissen, Sarah L; Johnson, Aaron W; Macefield, Vaughan G

    2015-01-01

    Low baroreflex sensitivity (BRS) is associated with elevated cardiovascular risk. However, the evidence is based primarily on measurements of cardiac BRS. It cannot be assumed that cardiac or sympathetic BRS alone represent a true reflection of baroreflex control of blood pressure. The aim of this study was to examine the relationship between spontaneous sympathetic and cardiac BRS in healthy, young individuals. Continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made under resting conditions in 50 healthy individuals (18–28 years). 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 by plotting R-R interval against systolic pressure using the sequence method. Significant sympathetic BRSinc and cardiac BRS slopes were obtained for 42 participants. A significant positive correlation was found between sympathetic BRSinc and cardiac BRS (r = 0.31, P = 0.049). Among this group, significant sympathetic baroreflex slopes were obtained for 39 participants when plotting total MSNA against diastolic pressure. In this subset, a significant positive correlation was observed between sympathetic BRStotal and cardiac BRS (r = 0.40, P = 0.012). When males and females were assessed separately, these modest relationships only remained significant in females. Analysis by gender revealed correlations in the females between sympathetic BRSinc and cardiac BRS (r = 0.49, P = 0.062), and between sympathetic BRStotal and cardiac BRS (r = 0.57, P = 0.025). These findings suggest that gender interactions exist in baroreflex control of blood pressure, and that cardiac BRS is not appropriate for estimating overall baroreflex function in healthy, young populations. This relationship warrants investigation in aging and clinical populations. PMID:26564059

  16. A rare adrenal incidentaloma: adrenal schwannoma.

    PubMed

    Adas, Mine; Ozulker, Filiz; Adas, Gokhan; Koc, Bora; Ozulker, Tamer; Sahin, Ilknur Mansuroglu

    2013-01-01

    Adrenal schwannoma is an extremely uncommon cause of incidentaloma. It originates from neural sheath Schwann cells of the adrenal gland. We report the case of a left adrenal schwannoma incidentally discovered in a 32-year-old woman during examination of bloated feeling and stomach ache. The patient was incidentally found to have a left adrenal mass of 9 cm on abdominal ultrasonography. Computed tomography (CT) of the abdomen and [(18)F] fluorodeoxyglucose positron emission tomography (PET) were also performed. Metabolic evaluation was unremarkable. Due to the large size of the tumor, left adrenalectomy was performed. The postoperative course was uneventful. Histological examination established the diagnosis of schwannoma. This diagnosis was supported by immunohistochemistry of S-100 and vimentin positivity. In conclusion, adrenal schwannoma is an extremely rare entity and can grow considerably in size. The present case report emphasizes that clinicians should be aware of the possibility of retroperitoneal schwannoma. Total excision of benign schwannoma is associated with a favorable outcome. To our knowledge, there are case reports of schwannoma with CT and magnetic resonance imaging findings in the literature, although this is the first schwannoma case with PET-CT imaging. PMID:24403879

  17. A Rare Adrenal Incidentaloma: Adrenal Schwannoma

    PubMed Central

    Adas, Mine; Ozulker, Filiz; Adas, Gokhan; Koc, Bora; Ozulker, Tamer; Sahin, Ilknur Mansuroglu

    2013-01-01

    Adrenal schwannoma is an extremely uncommon cause of incidentaloma. It originates from neural sheath Schwann cells of the adrenal gland. We report the case of a left adrenal schwannoma incidentally discovered in a 32-year-old woman during examination of bloated feeling and stomach ache. The patient was incidentally found to have a left adrenal mass of 9 cm on abdominal ultrasonography. Computed tomography (CT) of the abdomen and [18F] fluorodeoxyglucose positron emission tomography (PET) were also performed. Metabolic evaluation was unremarkable. Due to the large size of the tumor, left adrenalectomy was performed. The postoperative course was uneventful. Histological examination established the diagnosis of schwannoma. This diagnosis was supported by immunohistochemistry of S-100 and vimentin positivity. In conclusion, adrenal schwannoma is an extremely rare entity and can grow considerably in size. The present case report emphasizes that clinicians should be aware of the possibility of retroperitoneal schwannoma. Total excision of benign schwannoma is associated with a favorable outcome. To our knowledge, there are case reports of schwannoma with CT and magnetic resonance imaging findings in the literature, although this is the first schwannoma case with PET-CT imaging. PMID:24403879

  18. Adrenomyeloneuropathy Presenting With Adrenal Insufficiency

    PubMed Central

    Park, Hee Dong; Choi, Yong Min; Kang, Jin Ho

    2013-01-01

    Adrenomyeloneuropathy (AMN), one of the variants of X-linked adrenoleukodystrophy (ALD), is inherited peroxisomal disorder associated with the accumulation of very long chain fatty acids (VLCFA). AMN is characterized primarily by involvements of long ascending and descending tracts of the spinal cord and peripheral neuropathy, which leads to spastic paraparesis and urinary and erectile dysfunction. We experienced the AMN case of a 33-year-old man presenting bilateral progressive spastic paraparesis, impotence and urge incontinence with primary adrenal failures, as confirmed by increased serum of VLCFA concentrations. Considering that somatosensory evoked potentials in posterior tibial nerve was the only abnormal finding in electrophysiologic findings when compared with the severe spastic gait pattern shown, it is necessary to follow up with electrophysiologic studies. PMID:24020038

  19. Interactions between angiotensin peptides and the sympathetic nervous system mediating intestinal sodium and water absorption in the rat.

    PubMed Central

    Levens, N R; Peach, M J; Carey, R M

    1981-01-01

    The purpose of this study was to determine the locus of interaction of angiotensin peptides with the sympathetic nervous system leading to alterations in jejunal sodium and water transport. At low physiological doses, angiotensin II (AII) stimulates jejunal sodium and water absorption, while at high doses peptide inhibits absorption and/or stimulates secretion. Both the stimulation of jejunal transport and the inhibition of absorption were expressed in adrenalectomized rats. However, the stimulation of jejunal water absorption was abolished and a potentiated inhibition of transport was expressed in peripherally sympathectomized rats (intact adrenal medulla) and in normal rats after administration of guanethadine, phentolamine, and prazosin. The angiotensin analog (Sar1 Leu8)-AII has low efficacy and is a potent competitive antagonist of the parent peptide in pressor and myotropic systems, but is a full agonist with even greater potency than AII in stimulating jejunal transport. The increased water transport in response to (Sar1 Leu8)-AII is not secondary to enhanced renal renin release, as the analog also stimulated jejunal transport in the presence of captopril and after bilateral nephrectomy. The stimulation of absorption in response to (Sar1 Leu8)-AII alone or together with AII was abolished by phentolamine. These data demonstrate that AII-increased intestinal absorption is secondary to the release of norepinephrine from nerve endings in the jejunum and that AII inhibition of absorption is not mediated by the sympathetic nervous system. The analog (Sar1 Leu8)-AII is a full agonist in the stimulation of jejunal transport (increased norepinephrine release), but antagonizes the inhibitory response to high doses of AII. Angiotensin peptides are potent modulators of intestinal sodium and water absorption. PMID:7204574

  20. The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

    PubMed

    Lansdown, Andrew; Rees, D Aled

    2012-12-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. PMID:22882204

  1. The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

    PubMed

    Lansdown, Andrew; Rees, D Aled

    2012-12-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice.

  2. A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

    PubMed Central

    Carnevale, Daniela; Perrotta, Marialuisa; Pallante, Fabio; Fardella, Valentina; Iacobucci, Roberta; Fardella, Stefania; Carnevale, Lorenzo; Carnevale, Raimondo; De Lucia, Massimiliano; Cifelli, Giuseppe; Lembo, Giuseppe

    2016-01-01

    The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension. PMID:27676657

  3. Involvement of the hypothalamic--pituitary--adrenal/gonadal axis and the peripheral nervous system in rheumatoid arthritis: viewpoint based on a systemic pathogenetic role.

    PubMed

    Straub, R H; Cutolo, M

    2001-03-01

    From the compendium presented above, the following statements become evident: 1) Inappropriately low secretion of cortisol in relation to inflammation is a typical feature of the inflammatory disease in patients with RA. 2) The secretion of adrenal androgens is significantly reduced, which is a problem in postmenopausal women and elderly men due to a lack of downstream sex hormones. 3) Serum levels of testosterone are markedly reduced in RA. 4) Sympathetic nerve fibers are markedly reduced in the synovial tissue of patients with RA, whereas proinflammatory sensory fibers (substance P) are present. 5) Substance P serves to continuously sense painful stimuli in the periphery, and the nociceptive input from the inflamed joint shows a large amplification in the spinal cord. This leads to continuous pain with stabilization of the afferent sensory input and continuous release of proinflammatory substance P into the lumen of the joint. From these facts it is obvious that alterations of the systemic antiinflammatory feedback systems contribute significantly to the pathogenesis of RA. Disease therapy directed at these alterations must provide a mechanism to replace the adrenal glands (glucocorticoids), the gonadal glands (androgens), and the sympathetic nervous system (adenosine increase by low-dose MTX, sulfasalazine, and salicylates) in order to integrate their immunosuppressive effects at the local site of synovial inflammation. Although local processes of the adaptive immune system are important in pathogenesis in the acute phase of RA, these mechanisms may be less important during the chronic phase of the disease in the absence of a specific trigger. We believe that a defect of systemic antiinflammatory feedback systems is an important factor in the perpetuation of RA. This review reinforces the belief that combined therapeutic approaches on a neuroendocrine immune basis are of crucial importance in a pathogenetically oriented therapy of RA.

  4. Ghrelin inhibits sympathetic nervous activity in sepsis.

    PubMed

    Wu, Rongqian; Zhou, Mian; Das, Padmalaya; Dong, Weifeng; Ji, Youxin; Yang, Derek; Miksa, Michael; Zhang, Fangming; Ravikumar, Thanjavur S; Wang, Ping

    2007-12-01

    Our previous studies have shown that norepinephrine (NE) upregulates proinflammatory cytokines by activating alpha(2)-adrenoceptor. Therefore, modulation of the sympathetic nervous system represents a novel treatment for sepsis. We have also shown that a novel stomach-derived peptide, ghrelin, is downregulated in sepsis and that its intravenous administration decreases proinflammatory cytokines and mitigates organ injury. However, it remains unknown whether ghrelin inhibits sympathetic activity through central ghrelin receptors [i.e., growth hormone secretagogue receptor 1a (GHSR-la)] in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). Ghrelin was administered through intravenous or intracerebroventricular injection 30 min before CLP. Our results showed that intravenous administration of ghrelin significantly reduced the elevated NE and TNF-alpha levels at 2 h after CLP. NE administration partially blocked the inhibitory effect of ghrelin on TNF-alpha in sepsis. GHSR-la inhibition by the administration of a GHSR-la antagonist, [d-Arg(1),d-Phe(5), d-Trp(7,9),Leu(11)]substance P, significantly increased both NE and TNF-alpha levels even in normal animals. Markedly elevated circulating levels of NE 2 h after CLP were also significantly decreased by intracerebroventricular administration of ghrelin. Ghrelin's inhibitory effect on NE release was completely blocked by intracerebroventricular injection of the GHSR-1a antagonist or a neuropeptide Y (NPY)/Y(1) receptor antagonist. However, ghrelin's downregulatory effect on TNF-alpha release was only partially diminished by these agents. Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. Ghrelin's inhibitory effect on TNF-alpha production in sepsis is partially because of its modulation of the overstimulated sympathetic nerve activation.

  5. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    PubMed Central

    Jin, Heung Yong; Baek, Hong Sun

    2015-01-01

    Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed. PMID:26706915

  6. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy.

    PubMed

    Jin, Heung Yong; Baek, Hong Sun; Park, Tae Sun

    2015-12-01

    Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed. PMID:26706915

  7. 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.

  8. Adrenal insufficiency: diagnosis and management.

    PubMed

    Munver, Ravi; Volfson, Ilya A

    2006-01-01

    Adrenal insufficiency is a disorder characterized by hypoactive adrenal glands resulting in insufficient production of the hormones cortisol and aldosterone by the adrenal cortex. This disorder may develop as a primary failure of the adrenal cortex or be secondary to an abnormality of the hypothalamic-pituitary axis. Patients with adrenal insufficiency often are asymptomatic or they may present with fatigue, muscle weakness, weight loss, low blood pressure, and sometimes darkening of the skin. The presentation of adrenal insufficiency varies dramatically and poses a major diagnostic dilemma. This review focuses on the diagnosis and treatment of primary and secondary adrenal insufficiency.

  9. Comparison of bretylium and guanethidine: tolerance, and effects on adrenergic nerve function and responses to sympathomimetic amines

    PubMed Central

    Boura, A. L. A.; Green, A. F.

    1962-01-01

    Bretylium depresses the slope of regression lines relating frequency of sympathetic nerve stimulation to magnitude of contractions of the cat nictitating membrane. In contrast, guanethidine and reserpine preferentially abolish responses to low rates of nerve stimulation and cause a roughly parallel shift of the regression lines. The hypersensitivity of the nictitating membranes of cats to intravenous adrenaline or noradrenaline is far greater after a series of small daily doses of bretylium or guanethidine than after single large doses. The maximal sensitivity produced was similar to that after postganglionic sympathetic nerve section and exceeded that produced by ganglion blockade. The development of hypersensitivity to catechol amines is accompanied by some return of responses of the nictitating membranes to sympathetic nerve stimulation despite continued daily administration of bretylium or guanethidine. In cats given bretylium daily, responses to low rates of nerve stimulation become greater than in controls unless the dose of bretylium given subcutaneously is 50 mg/kg or more. When marked hypersensitivity to catechol amines has been produced by giving bretylium or guanethidine daily for 7 or 14 days, the sympathomimetic effects of these compounds are greater. Responses to intravenous dimethylphenylpiperazinium are also increased and the results suggest that even large daily doses of adrenergic neurone blocking agents do not appreciably impair the functioning of the adrenal medulla. The pressor effects of intravenous adrenaline, noradrenaline and dimethylphenylpiperazinium iodide increase less than the corresponding nictitating membrane responses. These results are discussed in relation to tolerance to adrenergic neurone blockade, and differences between the effects of bretylium and guanethidine found in man. Bretylium and guanethidine depress the slopes of the dose-response curves for the pressor and nictitating membrane contracting effects of tyramine. When

  10. Sympathetic neural outflow and chemoreflex sensitivity are related to spontaneous breathing rate in normal men.

    PubMed

    Narkiewicz, Krzysztof; van de Borne, Philippe; Montano, Nicola; Hering, Dagmara; Kara, Tomas; Somers, Virend K

    2006-01-01

    Respiration contributes importantly to short-term modulation of sympathetic nerve activity. However, the relationship between spontaneous breathing rate, chemoreflex function, and direct measures of sympathetic traffic in healthy humans has not been studied previously. We tested the hypothesis that muscle sympathetic nerve activity and chemoreflex sensitivity are linked independently to respiratory rate in normal subjects. We studied 69 normal male subjects aged 29.6+/-8.1 years. Subjects were subdivided according to the tertiles of respiratory rate distributions. Mean respiration rate was 10.6 breaths/min in the first tertile, 14.8 breaths/min in the second tertile, and 18.0 breaths/min in the third tertile. Subjects from the third tertile (faster respiratory rate) had greater sympathetic activity than subjects from the first tertile (slower respiratory rate; 29+/-3 versus 17+/-2 bursts/min; P<0.001). Stepwise multiple linear regression analysis revealed that only respiratory rate was linked independently to sympathetic activity (r=0.42; P<0.001). In comparison to subjects with slow respiratory rate, subjects with fast respiratory rate had greater increases in minute ventilation during both hypercapnia (7.3+/-0.8 versus 3.2+/-1.0 L/min; P=0.005) and hypoxia (5.7+/-0.8 versus 2.4+/-0.7 L/min; P=0.007). Muscle sympathetic nerve activity and chemoreflex sensitivity are linked to spontaneous respiratory rate in normal humans. Faster respiratory rate is associated with higher levels of sympathetic traffic and potentiated responses to hypoxia and hypercapnia. Spontaneous breathing frequency, central sympathetic outflow, and chemoreflex sensitivity exhibit significant and hitherto unrecognized interactions in the modulation of neural circulatory control.

  11. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

    NASA Technical Reports Server (NTRS)

    Levine, Benjamin D.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Zuckerman, Julie H.; Diedrich, Andre; Biaggioni, Italo; Ray, Chester A.; Smith, Michael L.; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Mano, Tadaaki; Zhang, Rong; Iwasaki, Kenichi; Lane, Lynda D.; Buckey, Jay C Jr; Cooke, William H.; Baisch, Friedhelm J.; Eckberg, Dwain L.; Blomqvist, C. Gunnar

    2002-01-01

    Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

  12. Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system.

    PubMed

    Molkov, Yaroslav I; Zoccal, Daniel B; Baekey, David M; Abdala, Ana P L; Machado, Benedito H; Dick, Thomas E; Paton, Julian F R; Rybak, Ilya A

    2014-01-01

    Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states.

  13. Sympathetic overactivity in active ulcerative colitis: effects of clonidine.

    PubMed

    Furlan, Raffaello; Ardizzone, Sandro; Palazzolo, Laura; Rimoldi, Alexandra; Perego, Francesca; Barbic, Franca; Bevilacqua, Maurizio; Vago, Luca; Bianchi Porro, Gabriele; Malliani, Alberto

    2006-01-01

    Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LF(RR); normalized units) and high-frequency (HF) parasympathetic (HF(RR); normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LF(SAP)), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LF(RR), LF/HF, and LF(SAP) were higher and HF(RR) was lower in patients than in controls. Tilt decreased HF(RR) and increased MSNA and LF(RR) less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LF(RR), and increased HF(RR), whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.

  14. Sympathetic innervation of the ileocecal junction in horses.

    PubMed

    Russo, D; Bombardi, C; Grandis, A; Furness, J B; Spadari, A; Bernardini, C; Chiocchetti, R

    2010-10-01

    The distribution and chemical phenotypes of sympathetic and dorsal root ganglion (DRG) neurons innervating the equine ileocecal junction (ICJ) were studied by combining retrograde tracing and immunohistochemistry. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) was investigated. Sympathetic neurons projecting to the ICJ were distributed within the celiac (CG), cranial mesenteric (CranMG), and caudal mesenteric (CaudMG) ganglia, as well as in the last ganglia of the thoracic sympathetic chain and in the splanchnic ganglia. In the CG and CranMG 91 +/- 8% and 93 +/- 12% of the neurons innervating the ICJ expressed TH- and DBH-IR, respectively. In the CaudMG 90 +/- 15% and 94 +/- 5% of ICJ innervating neurons were TH- and DBH-IR, respectively. Sympathetic (TH-IR) fibers innervated the myenteric and submucosal ganglia, ileal blood vessels, and the muscle layers. They were more concentrated at the ICJ level and were also seen encircling myenteric plexus (MP) and submucosal plexus (SMP) descending neurons that were retrogradely labeled from the ICJ. Among the few retrogradely labeled DRG neurons, nNOS-, CGRP-, and SP-IR nerve cells were observed. Dense networks of CGRP-, nNOS-, and SP-IR varicosities were seen around retrogradely labeled prevertebral ganglia neurons. The CGRP-IR fibers are probably the endings of neurons projecting from the intestine to the prevertebral ganglia. These findings indicate that this crucial region of the intestinal tract is strongly influenced by the sympathetic system and that sensory information of visceral origin influences the sympathetic control of the ICJ.

  15. [Mechanisms of adrenal embryogenesis].

    PubMed

    Barinov, E F; Sulaeva, O N

    2001-01-01

    The aim of this vie is to discuss the general principles of prenatal development of adrenal gland. On the basis of spatial-temporal heterogenity of structural particularites of fetal adrenal cortex, spectrum steroidogenic enzymes and secreting hormones expression in adrenocorticocytes, regulation of proliferation and differentiation processes mechanisms, authors discuss adrenal morphogenesis in three periods of gestation. It was noted the close relationship between placenta development and hypothalamo-pituitary-adrenocortical system formation with specification in each gestation period. Adrenal embryogenesis accompanied by remodeling of structural, functional and biochemical properties of parenchimal-stromal elements of fetal organ. Definitive zonation formation determined by morphogens: ACTH, renal and intraadrenal angiotensin II, estrogens, prostaglandines and other. The action of these factors realization is due to immediately and thought growth factor system (IGF-I, IGF-II, EGF, bFGF), working as paracrine amplificators of morphogenetic signals and activators of transcriptional factors--c-fos and c-jun.

  16. Acute adrenal crisis

    MedlinePlus

    ... condition that occurs when there is not enough cortisol. This is a hormone produced by the adrenal ... parts. The outer portion, called the cortex, produces cortisol. This is an important hormone for controlling blood ...

  17. Nicotine-induced exocytotic norepinephrine release in guinea-pig heart, human atrium and bovine adrenal chromaffin cells: modulation by single components of ischaemia.

    PubMed

    Krüger, C; Haunstetter, A; Gerber, S; Serf, C; Kaufmann, A; Kübler, W; Haass, M

    1995-08-01

    The influence of single components of myocardial ischaemia, such as anoxia, substrate withdrawal, hyperkalemia and extracellular acidosis, on nicotine-induced norepinephrine (NE) release was investigated in the isolated perfused guinea-pig heart, in incubated human atrial tissue and in cultured bovine adrenal chromaffin cells (BCC). In normoxia, nicotine (1-1000 mumol/l) evoked a concentration-dependent release of NE (determined by high pressure liquid chromatography and electrochemical detection) from guinea-pig heart and human atrium. In contrast to selective anoxia (Po2 < 5 mmHg) or glucose withdrawal, respectively, anoxia in combination with glucose withdrawal (5-40 min) markedly potentiated nicotine-induced NE release both in guinea-pig heart and human atrium. The sensitization of cardiac sympathetic nerve endings to nicotine was characterized by a lower threshold concentration and an approximate two-fold increase of maximum NE release, peaking after 10 min of anoxia and glucose withdrawal. Cyanide intoxication (1 mmol/l) combined with glucose withdrawal resulted in a similar increase of nicotine-induced sympathetic transmitter release both in guinea-pig heart and human atrium. In contrast, the nicotine-induced (10 mumol/l) NE overflow was only slightly potentiated by 10 min of global ischaemia in guinea-pig heart. Both hyperkalemia ([K+] 16 mmol/l) and acidosis (pH 6.8-6.0) distinctly attenuated the stimulatory effect of nicotine in guinea-pig heart and human atrium under normoxic conditions. Consistent with an exocytotic release mechanism, NE release was dependent on the presence of extracellular calcium under all conditions tested. Furthermore, NE overflow from guinea-pig heart was accompanied by a release of the exocytosis marker neuropeptide Y (NPY; determined by radioimmunoassay). In BCC, nicotine (1-10 mumol/l) evoked a release of NE and NPY and a transient rise of [Ca2+]i (determined with fura-2) during normoxia which were both dependent on the

  18. 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

  19. Effect of weightlessness on sympathetic-adrenomedullary activity of rats

    NASA Astrophysics Data System (ADS)

    Kvetňanský, R.; Torda, T.; Macho, L.; Tigranian, R. A.; Serova, L.; Genin, A. M.

    Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes—tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)—as well as CA-degrading enzymes—monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.

  20. Lumbar Sympathetic Block with Botulinum Toxin Type B for Complex Regional Pain Syndrome: A Case Study.

    PubMed

    Choi, Eunjoo; Cho, Chan Woo; Kim, Hye Young; Lee, Pyung Bok; Nahm, Francis Sahngun

    2015-01-01

    Lumbar sympathetic block (LSB) is an effective method for relief of sympathetically mediated pain in the lower extremities. To prolong the sympathetic blockade, sympathetic destruction with alcohol or radiofrequency has been used. The pre-ganglionic sympathetic nerves are cholinergic, and botulinum toxin (BTX) has been found to inhibit the release of acetylcholine at the cholinergic nerve terminals. Moreover, BTX type B (BTX-B) is more convenient to use than BTX type A. Based on these findings, we performed LSB on the 2 patients with complex regional pain syndrome (CRPS) in the lower extremity. Levobupivacaine 0.25% 5 mL mixed with BTX-B 5,000 IU was given under fluoroscopic guidance. Two months after LSB with BTX-B, pain intensity and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were significantly reduced. Allodynia and coldness disappeared and skin color came back to normal. In conclusion, BTX-B can produce an efficacious and durable sympathetic blocking effect on patients with CRPS.

  1. Muscle sympathetic activity in resting and exercising humans with and without heart failure.

    PubMed

    Notarius, Catherine F; Millar, Philip J; Floras, John S

    2015-11-01

    The sympathetic nervous system is critical for coordinating the cardiovascular response to various types of physical exercise. In a number of disease states, including human heart failure with reduced ejection fraction (HFrEF), this regulation can be disturbed and adversely affect outcome. The purpose of this review is to describe sympathetic activity at rest and during exercise in both healthy humans and those with HFrEF and outline factors, which influence these responses. We focus predominately on studies that report direct measurements of efferent sympathetic nerve traffic to skeletal muscle (muscle sympathetic nerve activity; MSNA) using intraneural microneurographic recordings. Differences in MSNA discharge between subjects with and without HFrEF both at rest and during exercise and the influence of exercise training on the sympathetic response to exercise will be discussed. In contrast to healthy controls, MSNA increases during mild to moderate dynamic exercise in the presence of HFrEF. This increase may contribute to the exercise intolerance characteristic of HFrEF by limiting muscle blood flow and may be attenuated by exercise training. Future investigations are needed to clarify the neural afferent mechanisms that contribute to efferent sympathetic activation at rest and during exercise in HFrEF.

  2. Muscle sympathetic activity in resting and exercising humans with and without heart failure.

    PubMed

    Notarius, Catherine F; Millar, Philip J; Floras, John S

    2015-11-01

    The sympathetic nervous system is critical for coordinating the cardiovascular response to various types of physical exercise. In a number of disease states, including human heart failure with reduced ejection fraction (HFrEF), this regulation can be disturbed and adversely affect outcome. The purpose of this review is to describe sympathetic activity at rest and during exercise in both healthy humans and those with HFrEF and outline factors, which influence these responses. We focus predominately on studies that report direct measurements of efferent sympathetic nerve traffic to skeletal muscle (muscle sympathetic nerve activity; MSNA) using intraneural microneurographic recordings. Differences in MSNA discharge between subjects with and without HFrEF both at rest and during exercise and the influence of exercise training on the sympathetic response to exercise will be discussed. In contrast to healthy controls, MSNA increases during mild to moderate dynamic exercise in the presence of HFrEF. This increase may contribute to the exercise intolerance characteristic of HFrEF by limiting muscle blood flow and may be attenuated by exercise training. Future investigations are needed to clarify the neural afferent mechanisms that contribute to efferent sympathetic activation at rest and during exercise in HFrEF. PMID:26481289

  3. Lumbar Sympathetic Block with Botulinum Toxin Type B for Complex Regional Pain Syndrome: A Case Study.

    PubMed

    Choi, Eunjoo; Cho, Chan Woo; Kim, Hye Young; Lee, Pyung Bok; Nahm, Francis Sahngun

    2015-01-01

    Lumbar sympathetic block (LSB) is an effective method for relief of sympathetically mediated pain in the lower extremities. To prolong the sympathetic blockade, sympathetic destruction with alcohol or radiofrequency has been used. The pre-ganglionic sympathetic nerves are cholinergic, and botulinum toxin (BTX) has been found to inhibit the release of acetylcholine at the cholinergic nerve terminals. Moreover, BTX type B (BTX-B) is more convenient to use than BTX type A. Based on these findings, we performed LSB on the 2 patients with complex regional pain syndrome (CRPS) in the lower extremity. Levobupivacaine 0.25% 5 mL mixed with BTX-B 5,000 IU was given under fluoroscopic guidance. Two months after LSB with BTX-B, pain intensity and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were significantly reduced. Allodynia and coldness disappeared and skin color came back to normal. In conclusion, BTX-B can produce an efficacious and durable sympathetic blocking effect on patients with CRPS. PMID:26431145

  4. A nerve growth factor-regulated messenger RNA encodes a new intermediate filament protein

    PubMed Central

    1988-01-01

    Differential screening of a cDNA library from the PC12 rat pheochromocytoma cell line previously revealed a clone, clone 73, whose corresponding mRNA is induced by nerve growth factor (NGF). Induction parallels NGF-stimulated PC12 differentiation from a chromaffinlike phenotype to a sympathetic neuronlike phenotype. We report that DNA sequence analysis reveals that clone 73 mRNA encodes an intermediate filament (IF) protein whose predicted amino acid sequence is distinct from the known sequences of other members of the IF protein family. The sequence has highest homology with desmin and vimentin and includes the highly conserved central alpha-helical rod domain with the characteristic heptad repeat of hydrophobic residues, but has lower homology in the amino-terminal head and carboxyl-terminal tail domains. The head domain contains a large number of serine residues which are potential phosphorylation sites. The expression of clone 73 in vivo in the nervous system of the adult rat was investigated by in situ hybridization of clone 73 probes to tissue sections. The mRNA is expressed at high levels in ganglia of the peripheral nervous system, including the superior cervical ganglion (sympathetic), ciliary ganglion (parasympathetic), and dorsal root ganglion (sensory). In the central nervous system, motor nuclei of cranial nerves III, IV, V, VI, VII, X, and XII as well as ventral horn motor neurons and a restricted set of other central nervous system nuclei express the clone 73 mRNA. Tissues apart from those of the nervous system did not in general express the mRNA, with only very low levels detected in adrenal gland. We discuss the implications of these results for the mechanism of NGF- induced PC12 cell differentiation, the pathways of neuronal development in vivo, and the possible function of the clone 73 IF protein and its relationship to other IF proteins. PMID:3339087

  5. [Adrenal pseudocyst; a case report].

    PubMed

    Minagawa, Tomonori; Nishizawa, Shuji; Nakayama, Tsuyoshi; Okaneya, Toshikazu

    2007-02-01

    We report a case of adrenal pseudocyst. A 35-year-old woman presented with palpation of right upper abdominal mass without tenderness. Abdominal computed tomographic scan showed a right retroperitoneal cystic mass 20 cm in diameter. The patient underwent complete resection of the mass, including the normal adrenal gland. The cyst contained 3100 ml of dark brown thrombotic liquid. Histopathological examination revealed adrenal pseudocyst with a thick figrocollagenous wall. The normal adrenal gland was compressed by the wall. Adrenal pseudocyst is a rare disease. The mechanisms of adrenal pseudocyst formation and their expanding nature are discussed.

  6. Sympathetic Solar Filament Eruptions

    NASA Astrophysics Data System (ADS)

    Wang, Rui; Liu, Ying D.; Zimovets, Ivan; Hu, Huidong; Dai, Xinghua; Yang, Zhongwei

    2016-08-01

    The 2015 March 15 coronal mass ejection as one of the two that together drove the largest geomagnetic storm of solar cycle 24 so far was associated with sympathetic filament eruptions. We investigate the relations between the different filaments involved in the eruption. A surge-like small-scale filament motion is confirmed as the trigger that initiated the erupting filament with multi-wavelength observations and using a forced magnetic field extrapolation method. When the erupting filament moved to an open magnetic field region, it experienced an obvious acceleration process and was accompanied by a C-class flare and the rise of another larger filament that eventually failed to erupt. We measure the decay index of the background magnetic field, which presents a critical height of 118 Mm. Combining with a potential field source surface extrapolation method, we analyze the distributions of the large-scale magnetic field, which indicates that the open magnetic field region may provide a favorable condition for F2 rapid acceleration and have some relation with the largest solar storm. The comparison between the successful and failed filament eruptions suggests that the confining magnetic field plays an important role in the preconditions for an eruption.

  7. Role of the sympathetic nervous system in hypertension and hypertension-related cardiovascular disease.

    PubMed

    Seravalle, Gino; Mancia, Giuseppe; Grassi, Guido

    2014-06-01

    A number of cardiovascular disease have been shown to be characterized by a marked increase in sympathetic drive to the heart and the peripheral circulation. This is the case for essential hypertension, congestive heart failure, cardiac arrhythmias, obesity, metabolic syndrome, obstructive sleep apnea, and chronic renal disease. This review focuses on the most recent findings documenting the role of sympathetic neural factors in the development and progression of the hypertensive state as well as in the pathogenesis of hypertension-related target organ damage. It also reviews the role of sympathetic neural factors in the development of cardiovascular diseases not necessarily strictly related to the hypertensive state, such as congestive heart failure, cardiac arrhythmias, obesity, metabolic syndrome and renal failure. The paper will finally review the pharmacological and non-pharmacological interventions acting on the sympathetic drive. Emphasis will be given to the new approaches, such as renal nerves ablation and carotid baroreceptor stimulation, which have been shown to exert sympathoinhibitory effects.

  8. Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine

    SciTech Connect

    Melon, P.G.; Boyd, C.J.; McVey, S. |

    1997-03-01

    Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog {sup 11}C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional {sup 11}C-hydroxyephedrine uptake and blood flow, as assessed with {sup 13}N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. 27 refs., 4 figs., 3 tabs.

  9. Gender affects sympathetic neurovascular control during postural stress.

    PubMed

    Shoemaker, J K; Hughson, R L; Sinoway, L I

    2002-07-01

    Sympathetic outflow increases during head-up tilt (HUT) to stabilize blood pressure in the presence of decreases in venous return and stroke volume (SV). Otherwise, orthostatic hypotension would develop. Gender differences in orthostatic tolerance have been noted but the mechanisms are still uncertain. More recently, Waters et al. reported in a limited sample, greater susceptibility of women to demonstrate orthostatic intolerance following space flight. Therefore, it is important to understand gender differences in reflex blood pressure regulation. Recently, we reported smaller increments in muscle sympathetic nerve activity (MSNA) in healthy women during graded HUT and a non-baroreflex cold pressor test. The purpose of this report is to examine the hypothesis that gender differences in blood pressure control during HUT are related to important variations in MSNA discharge patterns.

  10. Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

    PubMed

    Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

    2015-01-01

    In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia.

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

    PubMed Central

    Cox, James F; Tahvanainen, Kari UO; Kuusela, Tom A; Levine, Benjamin D; Cooke, William H; Mano, Tadaaki; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Ertl, Andrew C; Biaggioni, Italo; Diedrich, André; Robertson, Rose Marie; Zuckerman, Julie H; Lane, Lynda D; Ray, Chester A; White, Ronald J; Pawelczyk, James A; Buckey, Jay C; Baisch, Friedhelm J; Bomqvist, C Gunnar; Robertson, David; Eckberg, Dwain L

    2002-01-01

    When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38–44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445 % during 30 mmHg straining on earth and 792 % in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain. PMID:11773338

  12. 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.; Biaggioni, Italo; Diedrich, Andre; Robertson, Rose Marie; Zuckerman, Julie H.; Lane, Lynda D.; Ray, Chester A.; White, Ronald J.; Pawelczyk, James A.; Buckey, Jay C Jr; Baisch, Friedhelm J.; Blomqvist, C. Gunnar; Robertson, David; Eckberg, Dwain L.; Roberton, D. (Principal Investigator)

    2002-01-01

    When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

  13. What Is Adrenal Cortical Cancer?

    MedlinePlus

    ... include pheochromocytomas (which are most often benign) and neuroblastomas . This document is about tumors and cancers of ... does not discuss tumors of the adrenal medulla. Neuroblastoma s are covered in a separate document . Adrenal cortex ...

  14. [Giant adrenal myelolipoma].

    PubMed

    El Mejjad, Amine; Fekak, Hamid; Dakir, Mohamed; Sarf, Ismail; Manni, Ahmed; Meziane, Fethi

    2004-02-01

    Adrenal myelolipoma is a rare, benign, non-secreting tumour composed of adipose and haematopoietic tissue. The authors report a rare case of giant adrenal myelolipoma in a 53-year-old patient presenting with low back pain and a palpable flank mass on examination. CT scan suggested the diagnosis and surgical resection was indicated in view of the size and symptomatic nature of this mass. Histological examination confirmed the diagnosis. The outcome was favourable without recurrence after a follow-up of one year. The diagnosis of adrenal myelolipoma is based on radiology. Conservative management is generally sufficient for small asymptomatic tumours, but resection is required for large (> 5 cm) and/or symptomatic tumours.

  15. Cardiovascular effects of afferent renal nerve stimulation.

    PubMed

    Stella, A; Weaver, L; Golin, R; Genovesi, S; Zanchetti, A

    1987-01-01

    Electrical stimulation of afferent renal nerves elicits an increase in arterial pressure and heart rate. The hypertensive response is presumably due to the widespread activation of the sympathetic nervous system leading to peripheral vasoconstriction. Interestingly, the kidney does not appear involved in this reflex excitatory response to afferent renal nerve stimulation since changes in vascular conductances and excretory functions are equal in both the innervated and denervated kidney, and secondary to changes in renal perfusion pressure. In addition, no changes in renin release from either kidneys are observed during afferent renal nerve stimulation. It is likely that the electrical stimulation of afferent renal nerves activates other reflexes exerting an inhibitory influence on efferent renal nerve activity. Indeed, neural renorenal reflexes which tonically inhibit renal functions have clearly been demonstrated. Furthermore, preferential inhibition of efferent renal nerve activity by cardiopulmonary and sinoaortic receptors has recently been shown during activation of other visceral afferents.

  16. Sympathetic co-transmission: the coordinated action of ATP and noradrenaline and their modulation by neuropeptide Y in human vascular neuroeffector junctions.

    PubMed

    Pablo Huidobro-Toro, J; Verónica Donoso, M

    2004-10-01

    The historical role of noradrenaline as the predominant sympathetic neurotransmitter in vascular neuroeffector junctions has matured to include ATP and the modulator action of neuropeptide Y (NPY). Numerous studies with isolated blood vessels rings demonstrate the presence of key enzymes responsible for the synthesis of ATP, noradrenaline and NPY, their co-storage, and their electrically evoked release from sympathetic perivascular nerve terminals. Functional assays coincide to demonstrate the integral role of these neurochemicals in sympathetic reflexes. In addition, the detection of the diverse receptor populations for ATP, noradrenaline and NPY in blood vessels, either in the smooth muscle, endothelial cells or nerve endings, further contribute to the notion that sympathetic vascular reflexes encompass the orchestrated action of the noradrenaline and ATP, and their modulation by NPY. The future clinical opportunities of sympathetic co-transmission in the control of human cardiovascular diseases will be highlighted.

  17. Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

    NASA Technical Reports Server (NTRS)

    Sinoway, L.; Shenberger, J.; Leaman, G.; Zelis, R.; Gray, K.; Baily, R.; Leuenberger, U.

    1996-01-01

    We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary contraction (12 2-s contractions/min) evokes sympathoexcitation without significant engagement of metabolite-sensitive muscle afferents (B.A. Batman, J.C. Hardy, U.A. Leuenberger, M.B. Smith, Q.X. Yang and L.I. Sinoway. J. Appl. Physiol. 76: 1077-1081, 1994). This is in contrast to the sympathetic nervous system responses observed during fatiguing static forearm exercise where metabolite-sensitive afferents are the key determinants of sympathetic activation. In this report we examined whether forearm exercise training would attenuate sympathetic nervous system responses to rhythmic forearm exercise. We measured heart rate, mean arterial blood pressure (MAP), muscle sympathetic nerve activity (microneurography), plasma norepinephrine (NE), and NE spillover and clearance (tritiated NE kinetics) during nonfatiguing rhythmic forearm exercise before and after a 4-wk unilateral forearm training paradigm. Training had no effect on forearm mass, maximal voluntary contraction, or heart rate but did attenuate the increase in MAP (increase in MAP: from 15.2 +/- 1.8 before training to 11.4 +/- 1.4 mmHg after training; P < 0.017), muscle sympathetic nerve activity (increase in bursts: from 10.8 +/- 1.4 before training to 6.2 +/- 1.1 bursts/min after training; P < 0.030), and the NE spillover (increases in arterial spillover: from 1.3 +/- 0.2 before training to 0.6 +/- 0.2 nmol.min-1.m-2 after training, P < 0.014; increase in venous spillover: from 2.0 +/- 0.6 before training to 1.0 +/- 0.5 nmol.min-1.m-2 after training, P < 0.037) seen in response to exercise performed by the trained forearm. Thus forearm training reduces sympathetic responses during a nonfatiguing rhythmic handgrip paradigm that does not engage muscle metaboreceptors. We speculate that this effect is due to a conditioning-induced reduction in mechanically sensitive muscle afferent discharge.

  18. Adrenal venous sampling in a patient with adrenal Cushing syndrome

    PubMed Central

    Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

  19. Adrenal venous sampling in a patient with adrenal Cushing syndrome.

    PubMed

    Builes-Montaño, Carlos Esteban; Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia.

  20. In oculo transplants of myometrium from postpartum guinea pigs fail to support sympathetic reinnervation.

    PubMed

    Brauer, M M; Burnstock, G; Thrasivoulou, C; Cowen, T

    1998-11-01

    Sympathetic nerves to the enlarged fetus-containing region of the uterus undergo degenerative changes during late pregnancy and show slow regrowth after parturition. It is not known whether this unusual response of sympathetic nerves to smooth muscle hypertrophy is due to the sensitivity of short adrenergic neurons to hormonal changes, or whether the nerves respond to changes in the neurotrophic capacity of the target. We have investigated this question using in oculo transplantation. Small pieces of myometrium from the uterine horn of virgin guinea pigs, or from the region previously occupied by the placenta and fetus in postpartum guinea pigs, were transplanted into the anterior eye chamber. After 3 wk in oculo, the pattern of reinnervation of the transplants was assessed on whole mount stretch preparations stained for tyrosine hydroxylase. The histology of the transplants was examined in toluidine blue-stained semithin sections. Myometrial transplants from virgin donors and uterine artery transplants from both virgin and postpartum donors became organotypically reinnervated by sympathetic fibres from the host iris. In contrast, sympathetic nerves did not reinnervate myometrial transplants from postpartum donors, although they approached the transplants and became distributed in the surrounding connective tissue. All transplanted tissues showed a normal histological appearance. Both the myometrium and uterine artery from postpartum donors retained a hypertrophic appearance after 3 wk in oculo. We interpret these results to indicate that the degeneration of sympathetic nerves in late pregnancy, as well as their slow regrowth to the uterus after delivery, may be due to changes in uterine smooth muscle rather than a particular sensitivity of short adrenergic neurons to hormonal changes. PMID:10029184

  1. Angiotensin-(1-7) enhances the effects of angiotensin II on the cardiac sympathetic afferent reflex and sympathetic activity in rostral ventrolateral medulla in renovascular hypertensive rats.

    PubMed

    Li, Peng; Zhang, Feng; Sun, Hai-Jian; Zhang, Feng; Han, Ying

    2015-11-01

    Excessive sympathetic activity propels the pathogenesis and progression of organ damage in hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation in hypertension. Given the important role of the renin-angiotensin (Ang) system in regulating sympathetic outflow and cardiovascular activity, the present study aimed to investigate the roles of Ang-(1-7) in Ang II-induced CSAR and the sympathetic activation responses in the rostral ventrolateral medulla (RVLM) of hypertensive rats. The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension. Responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin were used to evaluate the CSAR in sinoaortic-denervated and cervical-vagotomized rats with anesthesia. Both Ang II and Ang-(1-7) in the RVLM caused greater increases in RSNA and MAP in 2K1C rats than in sham-operated (sham) rats and enhanced CSAR independently. RVLM pretreatment with Ang-(1-7) dose dependently augmented the effects of Ang II on RSNA, MAP, and CSAR in 2K1C rats. Mas receptor antagonist A-779 in the RVLM exhibited more powerful inhibitory effects on RSNA, MAP, and CSAR than the Ang II type 1 (AT1) receptor antagonist losartan. The expression of both the AT1 receptor and Mas receptor proteins in the RVLM increased, but neither the Ang II nor Ang-(1-7) levels in the RVLM changed significantly in the 2K1C rats compared with the sham rats. These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and sympathetic output not only by itself but also through enhancing the effects of Ang II in renovascular hypertensive rats. Both endogenous Ang-(1-7) and Ang II in the RVLM contribute to the enhanced CSAR and sympathetic activation in renovascular hypertension.

  2. [Tilt test and orthostatic intolerance: abnormalities in the neural sympathetic response to gravitational stimulus].

    PubMed

    Furlan, R

    2001-05-01

    In the present manuscript the different methodologies aimed at assessing the autonomic profile in humans during a gravitational stimulus have been described. In addition, strengths and drawbacks of the tilt test in relation to occasional orthostatic intolerance were addressed. Finally, different autonomic abnormalities underlying occasional and chronic orthostatic intolerance syndromes have been schematically highlighted. The direct recording of the neural sympathetic discharge from the peroneal nerve (MSNA), in spite of its invasive nature, still represents the recognized reference to quantify the changes in the sympathetic activity to the vessels attending postural modifications. The increase of plasma norepinephrine during a tilt test is achieved by both an increase in plasma spillover and a concomitant decrease in systemic clearance. Changes in the indices of cardiac sympathetic and vagal modulation may also be quantified during a tilt test by power spectrum analysis of RR interval variability. The spectral markers of cardiac autonomic control, if evaluated concomitantly with MSNA, may contribute to assess abnormalities in the regional distribution of the sympathetic activity to the heart and the vessels. The capability of the tilt test of reproducing a vasovagal event or of inducing "false positive responses" seems to be markedly affected by the age, thus suggesting that additional or different etiopathogenetic mechanisms might be involved in the loss of consciousness in older as compared to younger subjects. In subjects suffering from occasional or habitual neurally mediated syncope an increase or, respectively, a decrease in cardiac and vascular sympathetic modulation has been documented before the loss of consciousness. In patients with pure autonomic failure, a global dysautonomia affecting both the sympathetic and the vagal modulation to the heart, seems to be present. In chronic orthostatic intolerance, the most common form of dysautonomia of young women

  3. Sympathetic reaction tests and analyses

    NASA Technical Reports Server (NTRS)

    Ricardson, D. E.; Bowman, A. L.

    1980-01-01

    The critical separation distances for explosive reactions of a solid rocket propellant were measured. Explosive reactions included low order explosion, low order detonation, and high order detonation. The effects of sample size, shape, damage and temperature on sympathetic reaction were determined experimentally. The sympathetic detonation of small cubes of solid rocket propellant was modelled numerically, using the Eulerian reactive hydrodynamic code 2DE with Forest Fire burn rates. The model was applied to cubes of 2.54 - 7.62 cm (1 - 3 in.), with agreement between calculated and experimental results.

  4. Micropenis and congenital adrenal hypoplasia.

    PubMed

    Bourgeois, M J; Jones, B; Waagner, D C; Dunn, D

    1989-01-01

    Micropenis is often an early sign of congenital hypopituitarism. It has also been associated with congenital adrenal hypoplasia in infants with anencephaly and pituitary agenesis. This report is on two infants with micropenis and congenital adrenal hypoplasia. One presented with a similar clinical course and postmortem findings to previously reported cases of adrenal hypoplasia and pituitary agenesis. The other patient represents the first reported case of an infant with micropenis and congenital adrenal hypoplasia in the absence of pituitary agenesis. The histologic patterns of adrenal hypoplasia, as well as the etiologic and clinical implications of its association with micropenis, are discussed.

  5. Congenital adrenal hyperplasia

    MedlinePlus

    ... or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to 18,000 ... penis but normal testes Well-developed muscles Both boys and girls will be tall as children, but much shorter ...

  6. Role of renal sensory nerves in physiological and pathophysiological conditions

    PubMed Central

    2014-01-01

    Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

  7. Immunological Studies on Adrenal Glands

    PubMed Central

    Milgrom, Felix; Witebsky, Ernest

    1962-01-01

    Rabbits injected with a bovine adrenal suspension incorporated into Freund adjuvants produced antibodies reacting in a variety of serological tests with extracts of bovine adrenals as well as with extracts of other bovine organs. The double diffusion gel precipitation procedure and absorption experiments revealed that part of these antibodies were specific for adrenal only. In immunoelectrophoretic analysis the adrenal-specific reaction appeared as a line on the anodal part of the electrophoretic field. When extraction was performed at 100° and the extracts autoclaved at 120°, the adrenal-specific antigen remained unaltered, whereas all but one of the non-adrenal-specific antigens (i.e. antigens shared by other bovine organs) were destroyed. The adrenal-specific antigen was localized predominantly, if not exclusively, in the medulla. A similar or identical antigen was found in the adrenals of sheep but not in those of any other species tested. The adrenal-specific antigen was precipitated by ethanol at 72 per cent concentration; it was not destroyed by 90 per cent phenol extraction. Re-dissolved ethanol precipitate of boiled bovine adrenal extract incorporated into Freund adjuvants elicited production of adrenal-specific antibodies when injected into rabbits. ImagesFIG. 2FIG. 3FIG. 4FIG. 5FIG. 8 PMID:14473880

  8. Sympathetic regulation of cerebral blood flow during seizures in newborn lambs

    SciTech Connect

    Kurth, C.D.; Wagerle, L.C.; Delivoria-Papadopoulos, M. )

    1988-09-01

    The authors examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow was measured. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10-39% greater in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10-31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17-27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.

  9. Degenerative pathological irritations to cervical PLL may play a role in presenting sympathetic symptoms.

    PubMed

    Wang, Zhanchao; Wang, Xinwei; Yuan, Wen; Jiang, Dongjie

    2011-11-01

    The mechanism of cervical vertigo remains unknown. Stimulation of arterial vertebralis caused by osteophyte of the Luschka joint or segmental instability of the cervical spine was considered to be a potential factor contributing to it. Years of studies found that the ischemia of the vertebral artery is not directly correlated with the clinical symptoms of vertigo, and can not be used to explain cervical vertigo as a sole reason. As proven by clinical practical experience, the routine anterior cervical decompression and fusion (ACDF) procedure, in which the degenerative disc and posterior longitudinal ligament (PLL) were often removed, shows positive results for elimination of the sympathetic symptoms. In this article, we hypothesize that: (1) there are sympathetic nerve postganglionic fibers distributed in the PLL or discs; (2) pathological changes secondary to degeneration of the intervertebral disc may cause irritation of sympathetic nerve fibers in PLL or discs, leading to sympathetic symptoms via certain pathways; (3) removal of the PLL or stabilization of the segment which decreases the irritation to PLL will help to eliminate the sympathetic symptoms.

  10. Generation of Murine Sympathoadrenergic Progenitor-Like Cells from Embryonic Stem Cells and Postnatal Adrenal Glands

    PubMed Central

    Saxena, Shobhit; Wahl, Joachim; Huber-Lang, Markus S.; Stadel, Dominic; Braubach, Peter; Debatin, Klaus-Michael; Beltinger, Christian

    2013-01-01

    Sympathoadrenergic progenitor cells (SAPs) of the peripheral nervous system (PNS) are important for normal development of the sympathetic PNS and for the genesis of neuroblastoma, the most common and often lethal extracranial solid tumor in childhood. However, it remains difficult to isolate sufficient numbers of SAPs for investigations. We therefore set out to improve generation of SAPs by using two complementary approaches, differentiation from murine embryonic stem cells (ESCs) and isolation from postnatal murine adrenal glands. We provide evidence that selecting for GD2 expression enriches for ESC-derived SAP-like cells and that proliferating SAP-like cells can be isolated from postnatal adrenal glands of mice. These advances may facilitate investigations about the development and malignant transformation of the sympathetic PNS. PMID:23675538

  11. Generation of murine sympathoadrenergic progenitor-like cells from embryonic stem cells and postnatal adrenal glands.

    PubMed

    Saxena, Shobhit; Wahl, Joachim; Huber-Lang, Markus S; Stadel, Dominic; Braubach, Peter; Debatin, Klaus-Michael; Beltinger, Christian

    2013-01-01

    Sympathoadrenergic progenitor cells (SAPs) of the peripheral nervous system (PNS) are important for normal development of the sympathetic PNS and for the genesis of neuroblastoma, the most common and often lethal extracranial solid tumor in childhood. However, it remains difficult to isolate sufficient numbers of SAPs for investigations. We therefore set out to improve generation of SAPs by using two complementary approaches, differentiation from murine embryonic stem cells (ESCs) and isolation from postnatal murine adrenal glands. We provide evidence that selecting for GD2 expression enriches for ESC-derived SAP-like cells and that proliferating SAP-like cells can be isolated from postnatal adrenal glands of mice. These advances may facilitate investigations about the development and malignant transformation of the sympathetic PNS.

  12. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling

    PubMed Central

    Lehmann, Lorenz H.; Rostosky, Julia S.; Buss, Sebastian J.; Kreusser, Michael M.; Krebs, Jutta; Mier, Walter; Enseleit, Frank; Spiger, Katharina; Hardt, Stefan E.; Wieland, Thomas; Haass, Markus; Lüscher, Thomas F.; Schneider, Michael D.; Parlato, Rosanna; Gröne, Hermann-Josef; Haberkorn, Uwe; Yanagisawa, Masashi; Katus, Hugo A.; Backs, Johannes

    2014-01-01

    In preclinical studies, endothelin receptor A (ETA) antagonists (ETAi) attenuated the progression of heart failure (HF). However, clinical HF trials failed to demonstrate beneficial effects of ETAi. These conflicting data may be explained by the possibility that established HF drugs such as adrenergic receptor blockers interfered with the mechanism of ETAi action in clinical trials. Here we report that mice lacking ETA only in sympathetic neurons (SN-KO) showed less adverse structural remodeling and cardiac dysfunction in response to pathological pressure overload induced by transverse aortic constriction (TAC). In contrast, mice lacking ETA only in cardiomyocytes (CM-KO) were not protected. TAC led to a disturbed sympathetic nerve function as measured by cardiac norepinephrine (NE) tissue levels and [124I]-metaiodobenzylguanidine-PET, which was prevented in SN-KO. In a rat model of HF, ETAi improved cardiac and sympathetic nerve function. In cocultures of cardiomyocytes (CMs) and sympathetic neurons (SNs), endothelin-1 (ET1) led to a massive NE release and exaggerated CM hypertrophy compared with CM monocultures. ETA-deficient CMs gained a hypertrophic response through wild-type SNs, but ETA-deficient SNs failed to mediate exaggerated CM hypertrophy. Furthermore, ET1 mediated its effects indirectly via NE in CM-SN cocultures through adrenergic receptors and histone deacetylases, resulting in activation of the prohypertrophic transcription factor myocyte enhancer factor 2. In conclusion, sympathetic ETA amplifies ET1 effects on CMs through adrenergic signaling pathways. Thus, antiadrenergic therapies may blunt potentially beneficial effects of ETAi. Taken together, this may indicate that patients with β blocker intolerance or disturbed sympathetic nerve function could be evaluated for a potential benefit from ETAi. PMID:25197047

  13. Adrenergic vasoconstriction in peripheral nerves of the rabbit

    SciTech Connect

    Selander, D.; Mansson, L.G.; Karlsson, L.; Svanvik, J.

    1985-01-01

    The blood flow in the sciatic nerve of the rabbit was estimated from the wash out of intraneurally injected /sup 133/Xe. To avoid diffusion of the tracer into the surrounding muscular tissue, the nerve was covered by a gas-tight plastic film. Using this technique, the basal blood flow in the sciatic nerve was estimated to 35 ml X min-1 X 100 g-1. It was found that intraarterial norepinephrine and electrical stimulation of the lumbar sympathetic chain strongly reduced the wash out of /sup 133/Xe, which only can be explained by a pronounced reduction of the blood flow in the nerve itself. The blood flow again increased within 4 min of stopping the infusion of norepinephrine or the sympathetic stimulation. The prolonged effect and higher neurotoxicity of local anesthetics containing adrenaline may be explained by an alpha receptor-mediated vasoconstriction of the microvessels of peripheral nerves.

  14. Regulation of Glucose Tolerance and Sympathetic Activity by MC4R Signaling in the Lateral Hypothalamus

    PubMed Central

    Morgan, Donald A.; McDaniel, Latisha N.; Yin, Terry; Khan, Michael; Jiang, Jingwei; Acevedo, Michael R.; Walsh, Susan A.; Ponto, Laura L. Boles; Norris, Andrew W.; Lutter, Michael; Rahmouni, Kamal

    2015-01-01

    Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4RLHA signaling regulates glucose tolerance and sympathetic nerve activity. Restoring expression of MC4Rs specifically in the LHA improves glucose intolerance in obese MC4R-null mice without affecting body weight or circulating insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake identifies the interscapular brown adipose tissue (iBAT) as a primary source where glucose uptake is increased in MC4RLHA mice. Direct multifiber sympathetic nerve recording further reveals that sympathetic traffic to iBAT is significantly increased in MC4RLHA mice, which accompanies a significant elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation prevents the glucoregulatory effect of MC4RLHA signaling. These results identify a novel role for MC4RLHA signaling in the control of sympathetic nerve activity and glucose tolerance independent of energy balance. PMID:25605803

  15. Early sympathetic islet neuropathy in autoimmune diabetes: lessons learned and opportunities for investigation.

    PubMed

    Mundinger, Thomas O; Taborsky, Gerald J

    2016-10-01

    This review outlines the current state of knowledge regarding a unique neural defect of the pancreatic islet in autoimmune diabetes, one that we have termed early sympathetic islet neuropathy (eSIN). We begin with the findings that a majority of islet sympathetic nerves are lost near the onset of type 1, but not type 2, diabetes and that this nerve loss is restricted to the islet. We discuss later work demonstrating that while the loss of islet sympathetic nerves and the loss of islet beta cells in type 1 diabetes both require infiltration of the islet by lymphocytes, their respective mechanisms of tissue destruction differ. Uniquely, eSIN requires the activation of a specific neurotrophin receptor and we propose two possible pathways for activation of this receptor during the immune attack on the islet. We also outline what is known about the functional consequences of eSIN, focusing on impairment of sympathetically mediated glucagon secretion and its application to the clinical problem of insulin-induced hypoglycaemia. Finally, we offer our view on the important remaining questions regarding this unique neural defect.

  16. Sympathetic and sensory innervation of small intensely fluorescent (SIF) cells in rat superior cervical ganglion.

    PubMed

    Takaki, Fumiya; Nakamuta, Nobuaki; Kusakabe, Tatsumi; Yamamoto, Yoshio

    2015-02-01

    The sympathetic ganglion contains small intensely fluorescent (SIF) cells derived from the neural crest. We morphologically characterize SIF cells and focus on their relationship with ganglionic cells, preganglionic nerve fibers and sensory nerve endings. SIF cells stained intensely for tyrosine hydroxylase (TH), with a few cells also being immunoreactive for dopamine β-hydroxylase (DBH). Vesicular acetylcholine transporter (VAChT)-immunoreactive puncta were distributed around some clusters of SIF cells, whereas some SIF cells closely abutted DBH-immunoreactive ganglionic cells. SIF cells contained bassoon-immunoreactive products beneath the cell membrane at the attachments and on opposite sites to the ganglionic cells. Ganglion neurons and SIF cells were immunoreactive to dopamine D2 receptors. Immunohistochemistry for P2X3 revealed ramified nerve endings with P2X3 immunoreactivity around SIF cells. Triple-labeling for P2X3, TH and VAChT allowed the classification of SIF cells into three types based on their innervation: (1) with only VAChT-immunoreactive puncta, (2) with only P2X3-immunoreactive nerve endings, (3) with both P2X3-immunoreactive nerve endings and VAChT-immunoreactive puncta. The results of retrograde tracing with fast blue dye indicated that most of these nerve endings originated from the petrosal ganglion. Thus, SIF cells in the superior cervical ganglion are innervated by preganglionic fibers and glossopharyngeal sensory nerve endings and can be classified into three types. SIF cells might modulate sympathetic activity in the superior cervical ganglion. PMID:25416508

  17. Protocol for Culturing Sympathetic Neurons from Rat Superior Cervical Ganglia (SCG)

    PubMed Central

    Zareen, Neela; Greene, Lloyd A.

    2009-01-01

    The superior cervical ganglia (SCG) in rats are small, glossy, almond-shaped structures that contain sympathetic neurons. These neurons provide sympathetic innervations for the head and neck regions and they constitute a well-characterized and relatively homogeneous population (4). Sympathetic neurons are dependent on nerve growth factor (NGF) for survival, differentiation and axonal growth and the wide-spread availability of NGF facilitates their culture and experimental manipulation (2, 3, 6). For these reasons, cultured sympathetic neurons have been used in a wide variety of studies including neuronal development and differentiation, mechanisms of programmed and pathological cell death, and signal transduction (1, 2, 5, and 6). Dissecting out the SCG from newborn rats and culturing sympathetic neurons is not very complicated and can be mastered fairly quickly. In this article, we will describe in detail how to dissect out the SCG from newborn rat pups and to use them to establish cultures of sympathetic neurons. The article will also describe the preparatory steps and the various reagents and equipment that are needed to achieve this. PMID:19229183

  18. Genetic disorders involving adrenal development.

    PubMed

    Lin, Lin; Ferraz-de-Souza, Bruno; Achermann, John C

    2007-01-01

    The past decade has seen significant advances in our understanding of the genetic aetiology of several forms of adrenal failure that present in infancy or childhood. Several of these disorders affect adrenal development and are termed 'adrenal hypoplasia'. These conditions can be broadly divided into: (1) secondary forms of adrenal hypoplasia due to panhypopituitarism (e.g. HESX1, LHX4, SOX3) or abnormalities in ACTH synthesis (TPIT) or processing (e.g. POMC or PC1); (2) adrenal hypoplasia as part of an ACTH resistance syndrome [MC2R/ACTH receptor, MRAP, AAAS (triple A syndrome)], and (3) primary defects in the development of the adrenal gland itself (primary adrenal hypoplasia). Primary adrenal hypoplasia most commonly occurs in an X-linked form due to mutations in the nuclear receptor DAX1 (NR0B1) but can occur in a poorly understood recessive form or as part of the IMAGe (intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia, genitourinary anomalies) syndrome. Defining the molecular basis of these conditions can have significant clinical implications for management, counselling and presymptomatic diagnosis, as well as providing fascinating insight into normal and abnormal mechanisms of adrenal development in humans.

  19. Sympathetic Activation is Associated with Exercise Limitation in COPD.

    PubMed

    Haarmann, Helge; Folle, Jan; Nguyen, Xuan Phuc; Herrmann, Peter; Heusser, Karsten; Hasenfuß, Gerd; Andreas, Stefan; Raupach, Tobias

    2016-10-01

    Exercise intolerance, skeletal muscle dysfunction, and reduced daily activity are central in COPD patients and closely related to quality of life and prognosis. Studies assessing muscle exercise have revealed an increase in sympathetic outflow as a link to muscle hypoperfusion and exercise limitation. Our primary hypothesis was that muscle sympathetic nerve activity (MSNA) correlates with exercise limitation in COPD. MSNA was evaluated at rest and during dynamic or static handgrip exercise. Additionally, we assessed heart rate, blood pressure, CO2 tension, oxygen saturation (SpO2), and breathing frequency. Ergospirometry was performed to evaluate exercise capacity. We assessed MSNA of 14 COPD patients and 8 controls. In patients, MSNA was negatively correlated with peak oxygen uptake (VO2% pred) (r = -0.597; p = 0.040). During dynamic or static handgrip exercise, patients exhibited a significant increase in MSNA, which was not observed in the control group. The increase in MSNA during dynamic handgrip was highly negatively correlated with peak exercise capacity in Watts (w) and peak oxygen uptake (VO2/kg) (r = -0.853; p = 0.002 and r = -0.881; p = 0.002, respectively). Our study reveals an association between increased MSNA and limited exercise capacity in patients with COPD. Furthermore, we found an increased sympathetic response to moderate physical exercise (handgrip), which may contribute to exercise intolerance in COPD. PMID:26829234

  20. Sympathetic vascular transduction is augmented in young normotensive blacks

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.

  1. Truths, errors, and lies around "reflex sympathetic dystrophy" and "complex regional pain syndrome".

    PubMed

    Ochoa, J L

    1999-10-01

    The shifting paradigm of reflex sympathetic dystrophy-sympathetically maintained pains-complex regional pain syndrome is characterized by vestigial truths and understandable errors, but also unjustifiable lies. It is true that patients with organically based neuropathic pain harbor unquestionable and physiologically demonstrable evidence of nerve fiber dysfunction leading to a predictable clinical profile with stereotyped temporal evolution. In turn, patients with psychogenic pseudoneuropathy, sustained by conversion-somatization-malingering, not only lack physiological evidence of structural nerve fiber disease but display a characteristically atypical, half-subjective, psychophysical sensory-motor profile. The objective vasomotor signs may have any variety of neurogenic, vasogenic, and psychogenic origins. Neurological differential diagnosis of "neuropathic pain" versus pseudoneuropathy is straight forward provided that stringent requirements of neurological semeiology are not bypassed. Embarrassing conceptual errors explain the assumption that there exists a clinically relevant "sympathetically maintained pain" status. Errors include historical misinterpretation of vasomotor signs in symptomatic body parts, and misconstruing symptomatic relief after "diagnostic" sympathetic blocks, due to lack of consideration of the placebo effect which explains the outcome. It is a lie that sympatholysis may specifically cure patients with unqualified "reflex sympathetic dystrophy." This was already stated by the father of sympathectomy, René Leriche, more than half a century ago. As extrapolated from observations in animals with gross experimental nerve injury, adducing hypothetical, untestable, secondary central neuron sensitization to explain psychophysical sensory-motor complaints displayed by patients with blatantly absent nerve fiber injury, is not an error, but a lie. While conceptual errors are not only forgivable, but natural to inexact medical science, lies

  2. CT demonstration of bilateral adrenal hemorrhage

    SciTech Connect

    Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.

    1983-08-01

    Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.

  3. SAH pituitary adrenal dysfunction.

    PubMed

    Vespa, P

    2011-09-01

    Disruption of the hypothalamic-pituitary-adrenal axis may occur after aneurysmal subarachnoid hemorrhage, resulting in hypopituitarism. An electronic literature search was conducted to identify articles with English-language abstracts published between 1980 and March 2011 that addressed hypothalamic-pituitary-adrenal axis insufficiency and hormone replacement. A total of 18 observational and prospective, randomized studies were selected for this review. Limited data are available evaluating pituitary effects during the acute stage after subarachnoid hemorrhage, with inconsistent results reported. Overall, acutely after subarachnoid hemorrhage, cortisol levels may initially be supranormal, decreasing toward normal levels over time. During the months to years after subarachnoid hemorrhage, pituitary deficiency may occur in up to one in three patients. Limited data suggest modest outcome benefits with fludrocortisone and no benefit or harm from corticosteroids. PMID:21800209

  4. Thyroid and adrenal relationships

    PubMed Central

    Parsons, Victor; Ramsay, Ian

    1968-01-01

    A brief review of the actions of adrenal medullary and thyroid hormones is presented and the ways in which they interact are examined. It is concluded that thyroid hormone produces the necessary intracellular environment without which the steady state and emergency actions of cathecholamines would be vitiated. In hyperthyroidism the increased concentration of thyroid hormones results in a lowering of the threshold for catecholamine action. For this reason it is possible to alleviate many of the symptoms of thyrotoxicosis by means of drugs which block β-adrenergic receptors. Attention is also drawn to the simultaneous occurrence of thyroid and adrenal disease, in the hope that this will encourage the search for further links in this field of endocrinology. PMID:5655216

  5. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Update Date 6/1/2015 ...

  6. Radioguided Adrenal Surgery

    PubMed Central

    Deus, Javier; Millera, Alfonso; Andrés, Alejandro; Prats, Enrique; Gil, Ismael; Suarez, Manuel; Salcini, José L.; Lahoz, Manuel

    2015-01-01

    Abstract The laparoscopic adrenalectomy is considered as the procedure of choice for the treatment of adrenal hyperplasia and tumor lesions. However, some special situations may limit the use of this method due to the difficulty to locate the gland and perform the lesion excision. We analyze 2 patients of a left adrenal tumor, explaining how they have overcome the difficulties in both situations. The first case was a patient with a history of intra-abdominal surgery and the other patient suffered from severe obesity. We performed with the use of the gamma probe, and the 2 cases, was of great help to access and glandular localization. The help of gamma probe test was achieved in the surgical bed, that removal was complete. The use of the portable gamma probe facilitated the access to the left adrenal gland as well as conducting the glandular excision without delay, despite the difficulties due to the intra abdominal surgery caused by the previous surgery, and in the case of severe obesity. PMID:26426608

  7. Adrenal Schwannoma: A Rare Incidentaloma.

    PubMed

    Kumar, Sumit; Karthikeyan, Vilvapathy S; Manohar, Chikkamoga S; Sreelakshmi, K; Shivalingaiah, Maregowda

    2016-08-01

    Adrenal schwannomas are very rare tumours that are difficult to diagnose preoperatively. A 42-year-old male presented with epigastric pain and indigestion. He had history of repeated operations for recurrent facial swelling on both sides of face diagnosed as Angiolymphoid Hyperplasia with Eosinophilia (ALHE). Physical examination revealed right facial swelling. Laboratory tests showed no evidence of hormonal hypersecretion. CECT abdomen showed a well-defined heterogenously enhancing right adrenal mass (5x4cm). Patient underwent right adrenalectomy. Histopathology revealed adrenal schwannoma, confirmed by immunohistochemistry (IHC) showing diffuse expression of S-100. Fine-needle aspiration biopsy of facial lesion confirmed ALHE recurrence. Less than 35 cases have been reported. Diagnosis of adrenal schwannoma on imaging studies is very difficult and surgical resection when performed for non-functioning adrenal masses >4cm clinches the diagnosis. Adrenal schwannoma is highly uncommon and was incidentally associated with recurrent ALHE. PMID:27656499

  8. The human sympathetic nervous system: its relevance in hypertension and heart failure.

    PubMed

    Parati, Gianfranco; Esler, Murray

    2012-05-01

    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  9. The human sympathetic nervous system: its relevance in hypertension and heart failure.

    PubMed

    Parati, Gianfranco; Esler, Murray

    2012-05-01

    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  10. Differences in CART expression and cell cycle behavior discriminate sympathetic neuroblast from chromaffin cell lineages in mouse sympathoadrenal cells.

    PubMed

    Chan, Wing Hei; Gonsalvez, David G; Young, Heather M; Southard-Smith, E Michelle; Cane, Kylie N; Anderson, Colin R

    2016-02-01

    Adrenal medullary chromaffin cells and peripheral sympathetic neurons originate from a common sympathoadrenal (SA) progenitor cell. The timing and phenotypic changes that mark this lineage diversification are not fully understood. The present study investigated the expression patterns of phenotypic markers, and cell cycle dynamics, in the adrenal medulla and the neighboring suprarenal ganglion of embryonic mice. The noradrenergic marker, tyrosine hydroxylase (TH), was detected in both presumptive adrenal medulla and sympathetic ganglion cells, but with significantly stronger immunostaining in the former. There was intense cocaine and amphetamine-regulated transcript (CART) peptide immunostaining in most neuroblasts, whereas very few adrenal chromaffin cells showed detectable CART immunostaining. This phenotypic segregation appeared as early as E12.5, before anatomical segregation of the two cell types. Cell cycle dynamics were also examined. Initially, 88% of Sox10 positive (+) neural crest progenitors were proliferating at E10.5. Many SA progenitor cells withdrew from the cell cycle at E11.5 as they started to express TH. Whereas 70% of neuroblasts (TH+/CART+ cells) were back in the cell cycle at E12.5, only around 20% of chromaffin (CART negative) cells were in the cell cycle at E12.5 and subsequent days. Thus, chromaffin cell and neuroblast lineages showed differences in proliferative behavior from their earliest appearance. We conclude that the intensity of TH immunostaining and the expression of CART permit early discrimination of chromaffin cells and sympathetic neuroblasts, and that developing chromaffin cells exhibit significantly lower proliferative activity relative to sympathetic neuroblasts.

  11. Hypothalamic paraventricular nucleus lesion involvement in the sympathetic control of lipid mobilization.

    PubMed

    Foster, Michelle T; Song, C Kay; Bartness, Timothy J

    2010-04-01

    The sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) is the principal initiator of lipolysis. Using pseudorabies virus, a transneuronal viral tract tracer, brain sites involved in the SNS outflow to WAT have been identified previously by us. One of these sites, the hypothalamic paraventricular nucleus (PVH) that shows predominantly unilateral sympathetic outflow from each half of the nucleus to ipsilaterally located WAT depots, was tested for laterality in lipid accumulation/mobilization in Siberian hamsters. First we tested whether unilateral PVH electrolytic lesions (PVHx) would increase lipid accumulation in WAT pads ipsilateral to the side of the PVHx. PVHx significantly increased body and WAT pad masses compared with sham PVHx; however, there was no laterality effect. In addition, bilateral PVHx increased body and WAT pad masses, as well as food intake, to a greater extent than did unilateral PVHx. We next tested for possible laterality effects on WAT lipid mobilization using food deprivation as the lipolytic stimulus in hamsters bearing unilateral or bilateral PVHx. Lipid mobilization was not prevented, as indicated indirectly by WAT mass and thus laterality of lipid mobilization could not be tested. We then tested whether removal of adrenal catecholamines via adrenal demedullation (ADMEDx) alone, or combined with bilateral PVHx, would block food deprivation-induced lipid mobilization, but neither did so. These results suggest that an intact PVH is not necessary for food deprivation-induced lipid mobilization and support the primacy of the SNS innervation of WAT, rather than adrenal medullary catecholamines, for lipid mobilization from WAT.

  12. Stimulated skin wrinkling as an indicator of limb sympathetic function.

    PubMed

    Wilder-Smith, Einar P V

    2015-01-01

    Skin wrinkling upon water immersion has been used as an indicator of limb nerve function for more than 80years. Until recently, routine use of the test has been hampered by a poor understanding of the physiology and lack of standardization. The process underlying stimulated skin wrinkling has been recently identified as dependent on digital vasoconstriction mediated via sympathetic nerve fibers. Vasoconstriction is postulated to drive wrinkling through loss of digit volume, which induces a negative pressure in the digit pulp and exerts a downward pull on the overlying skin and ultimately results in wrinkles. Improved test standardization has been achieved through substituting water with EMLA for inducing skin wrinkling. This has made testing much easier and has helped implement stimulated skin wrinkling as a practical routine clinical bedside test. A literature search identified 10 studies of sufficient quality for evaluating stimulated skin wrinkling as a diagnostic test of sympathetic under or over function. Seven studies provide level 1 or 2 evidence as a diagnostic test of small fiber neuropathy and three provide level 1 or 2 evidence for cystic fibrosis. There is reasonable evidence allowing the test to be employed as a simple and effective marker for small fiber neuropathy and cystic fibrosis.

  13. Increased excitability and spontaneous activity of rat sensory neurons following in vitro stimulation of sympathetic fiber sprouts in the isolated dorsal root ganglion

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming

    2010-01-01

    Many chronic pain conditions including complex regional pain syndrome are exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout into the dorsal root ganglia (DRG) after peripheral nerve injury, forming abnormal connections with sensory neurons. However, functional studies of sympathetic-sensory connections have been limited largely to in vivo studies. This study describes a new method for studying sympathetic-sensory connections in an isolated whole DRG preparation in the rat spinal nerve ligation (SNL) model. Three days after ligation of the ventral ramus of the spinal nerve (SNL), sympathetic fibers sprouting into the DRG were observed to originate largely in the intact dorsal ramus of the spinal nerve, which at the lumbar level is a small branch of the spinal nerve separating from the ventral ramus near the intervertebral foramen. In whole DRG isolated 3 days after SNL, microelectrode recordings of sensory neurons showed that repeated stimulation of the dorsal ramus enhanced spontaneous activity in large and medium diameter neurons, and reduced rheobase in large neurons. These effects, which were slow and long-lasting, were attributed to stimulation of the sympathetic sprouts because: stimulation had no effect in uninjured DRG; and effects could be reduced or eliminated by a “cocktail” of antagonists of norepinephrine and ATP receptors, by pretreatment with the sympathetic release blocker bretylium, or by pre-cutting the grey ramus through which sympathetic fibers coursed to the ligated DRG. The latter treatment, a relatively minimal form of sympathectomy, was also highly effective in reducing mechanical pain ipsilateral to the SNL. PMID:20800969

  14. A Demonstration of Sympathetic Cotransmission

    ERIC Educational Resources Information Center

    Johnson, Christopher D.

    2010-01-01

    Currently, most undergraduate textbooks that cover the autonomic nervous system retain the concept that autonomic nerves release either acetylcholine or norepinephrine. However, in recent years, a large volume of research has superseded this concept with one in which autonomic nerves normally release at least one cotransmitter along with a…

  15. Sympathetic restraint of muscle blood flow during hypoxic exercise

    PubMed Central

    Stickland, Michael K.; Smith, Curtis A.; Soriano, Benjamin J.; Dempsey, Jerome A.

    2009-01-01

    Control of exercising muscle blood flow is a balance between local vasodilatory factors and the increase in global sympathetic vasoconstrictor outflow. Hypoxia has been shown to potentiate the muscle sympathetic nerve response to exercise, potentially limiting the increase in muscle blood flow. Accordingly, we investigated sympathetic restraint to exercising muscle during whole body exercise in hypoxia. Six dogs chronically instrumented with ascending aortic and hindlimb flow probes and a terminal aortic catheter were studied at rest and mild [2.5 miles/h (mph), 5% grade] and moderate (4.0 mph, 10% grade) exercise while breathing room air or hypoxia (PaO2 ∼45 mmHg) in the intact control condition and following systemic α-adrenergic blockade (phentolamine). Hypoxia caused an increase in cardiac output (CO), hindlimb flow (FlowL), and blood pressure (BP), while total (CondT) and hindlimb conductance (CondL) were unchanged at rest and mild exercise but increased with moderate exercise. During both mild and moderate exercise, α-blockade in normoxia resulted in significant vasodilation as evidenced by increases in CO (10%), FlowL (17%), CondT (33%), CondL (43%), and a decrease in BP (−18%), with the increase in CondL greater than the increase in CondT during mild exercise. Compared with the normoxic response, α-blockade in hypoxia during exercise resulted in a significantly greater increase in CondT (59%) and CondL (74%) and a correspondingly greater decrease in BP (−34%) from baseline. These findings indicate that there is considerable hypoxia-induced sympathetic restraint of muscle blood flow during both mild and moderate exercise, which helps to maintain arterial blood pressure in hypoxia. PMID:19297541

  16. Artifacts produced during electrical stimulation of the vestibular nerve in cats. [autonomic nervous system components of motion sickness

    NASA Technical Reports Server (NTRS)

    Tang, P. C.

    1973-01-01

    Evidence is presented to indicate that evoked potentials in the recurrent laryngeal, the cervical sympathetic, and the phrenic nerve, commonly reported as being elicited by vestibular nerve stimulation, may be due to stimulation of structures other than the vestibular nerve. Experiments carried out in decerebrated cats indicated that stimulation of the petrous bone and not that of the vestibular nerve is responsible for the genesis of evoked potentials in the recurrent laryngeal and the cervical sympathetic nerves. The phrenic response to electrical stimulation applied through bipolar straight electrodes appears to be the result of stimulation of the facial nerve in the facial canal by current spread along the petrous bone, since stimulation of the suspended facial nerve evoked potentials only in the phrenic nerve and not in the recurrent laryngeal nerve. These findings indicate that autonomic components of motion sickness represent the secondary reactions and not the primary responses to vestibular stimulation.

  17. Etiopathogeny of Primary Adrenal Hypercortisolism.

    PubMed

    Vélayoudom-Céphise, Fritz-Line; Haissaguerre, Magali; Tabarin, Antoine

    2016-01-01

    Primary adrenal hypercortisolism is mainly due to cortisol-producing adrenocortical adenomas, bilateral micronodular or macronodular disease, and adrenal carcinomas. Important advances in the pathophysiology of primary adrenal hypercortisolism have been made in the last few years, partly through the use of new molecular biology tools. Most adrenal abnormalities leading to increased cortisol production involve somatic or germinal mutations of genes encoding elements of the cyclic AMP/protein kinase A signaling pathway, as shown in adrenal adenomas in 2014. One peculiar condition is primary macronodular adrenal hyperplasia (PMAH), which has given rise to new pathophysiological concepts such as regulation of cortisol secretion by illegitimate ligands through aberrant expression of G protein-coupled transmembrane receptors in adrenal nodules and stimulation of cortisol production by local adrenocorticotropic hormone production through autocrine/paracrine mechanisms. These findings provide a basis for the development of targeted therapies as an alternative to surgery. The recent identification of germinal mutations of ARMC5 in PMAH raises the possibility that this is much more frequently an inherited disease than previously suspected. It also offers the possibility of earlier diagnosis of PMAH by genetic screening and, hopefully, of earlier intervention to prevent the onset of hypercortisolism and its complications. The pathophysiology of Cushing's syndrome associated with a subset of adrenal adenomas, including subclinical cortisol-secreting incidentalomas and adrenal carcinomas, remains to be determined. PMID:27212135

  18. Adrenal crisis secondary to bilateral adrenal haemorrhage after hemicolectomy

    PubMed Central

    Tsang, Venessa H M; Kabir, Shahrir; Ip, Julian C Y

    2016-01-01

    Summary Adrenal haemorrhage is a rare cause of adrenal crisis, which requires rapid diagnosis, prompt initiation of parenteral hydrocortisone and haemodynamic monitoring to avoid hypotensive crises. We herein describe a case of bilateral adrenal haemorrhage after hemicolectomy in a 93-year-old female with high-grade colonic adenocarcinoma. This patient’s post-operative recovery was complicated by an acute hypotensive episode, hypoglycaemia and syncope, and subsequent computed tomography (CT) scan of the abdomen revealed bilateral adrenal haemorrhage. Given her labile blood pressure, intravenous hydrocortisone was commenced with rapid improvement of blood pressure, which had incompletely responded with fluids. A provisional diagnosis of hypocortisolism was made. Initial heparin-induced thrombocytopenic screen (HITTS) was positive, but platelet count and coagulation profile were both normal. The patient suffered a concurrent transient ischaemic attack with no neurological deficits. She was discharged on a reducing dose of oral steroids with normal serum cortisol levels at the time of discharge. She and her family were educated about lifelong steroids and the use of parenteral steroids should a hypoadrenal crisis eventuate. Learning points: Adrenal haemorrhage is a rare cause of hypoadrenalism, and thus requires prompt diagnosis and management to prevent death from primary adrenocortical insufficiency. Mechanisms of adrenal haemorrhage include reduced adrenal vascular bed capillary resistance, adrenal vein thrombosis, catecholamine-related increased adrenal blood flow and adrenal vein spasm. Standard diagnostic assessment is a non-contrast CT abdomen. Intravenous hydrocortisone and intravenous substitution of fluids are the initial management. A formal diagnosis of primary adrenal insufficiency should never delay treatment, but should be made afterwards.

  19. Traumatic and non-traumatic adrenal emergencies.

    PubMed

    Chernyak, Victoria; Patlas, Michael N; Menias, Christine O; Soto, Jorge A; Kielar, Ania Z; Rozenblit, Alla M; Romano, Luigia; Katz, Douglas S

    2015-12-01

    Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.

  20. The Evolution and Technique of Nerve-Sparing Retroperitoneal Lymphadenectomy.

    PubMed

    Masterson, Timothy A; Cary, Clint; Rice, Kevin R; Foster, Richard S

    2015-08-01

    The evolution of retroperitoneal lymph node dissection technique and associated template modifications for nonseminomatous germ cell tumors have resulted in significant improvement in the long-term morbidity. Through the preservation of sympathetic nerves via exclusion from or prospective identification within the boundaries of resection, maintenance and recovery of antegrade ejaculation are achieved. Nerve-sparing strategies in early-stage disease are feasible in most patients. Postchemotherapy, select patients can be considered for nerve preservation. This article describes the anatomic and physiologic basis for, indications and technical aspects of, and functional and oncologic outcomes reported after nerve-sparing retroperitoneal lymphadenectomy in testicular cancer. PMID:26216818

  1. Ganglioneuromas involving the hypoglossal nerve and the vagus nerve in a child: Surgical difficulties.

    PubMed

    Bakshi, Jaimanti; Mohammed, Abdul Wadood; Lele, Saudamini; Nada, Ritambra

    2016-02-01

    Ganglioneuromas are benign tumors that arise from the Schwann cells of the autonomic nervous system. They are usually seen in the posterior mediastinum and the paraspinal retroperitoneum in relation to the sympathetic chain. In the head and neck, they are usually related to the cervical sympathetic ganglia or to the ganglion nodosum of the vagus nerve or the hypoglossal nerve. We describe what we believe is the first reported case of multiple ganglioneuromas of the parapharyngeal space in which two separate cranial nerves were involved. The patient was a 10-year-old girl who presented with a 2-year history of a painless and slowly progressive swelling on the left side of her neck and a 1-year history hoarseness. She had no history of relevant trauma or surgery. Intraoperatively, we found two tumors in the left parapharyngeal space-one that had arisen from the hypoglossal nerve and the other from the vagus nerve. Both ganglioneuromas were surgically removed, but the affected nerves had to be sacrificed. Postoperatively, the patient exhibited hypoglossal nerve and vocal fold palsy, but she was asymptomatic. In addition to the case description, we discuss the difficulties we faced during surgical excision. PMID:26930339

  2. Ganglioneuromas involving the hypoglossal nerve and the vagus nerve in a child: Surgical difficulties.

    PubMed

    Bakshi, Jaimanti; Mohammed, Abdul Wadood; Lele, Saudamini; Nada, Ritambra

    2016-02-01

    Ganglioneuromas are benign tumors that arise from the Schwann cells of the autonomic nervous system. They are usually seen in the posterior mediastinum and the paraspinal retroperitoneum in relation to the sympathetic chain. In the head and neck, they are usually related to the cervical sympathetic ganglia or to the ganglion nodosum of the vagus nerve or the hypoglossal nerve. We describe what we believe is the first reported case of multiple ganglioneuromas of the parapharyngeal space in which two separate cranial nerves were involved. The patient was a 10-year-old girl who presented with a 2-year history of a painless and slowly progressive swelling on the left side of her neck and a 1-year history hoarseness. She had no history of relevant trauma or surgery. Intraoperatively, we found two tumors in the left parapharyngeal space-one that had arisen from the hypoglossal nerve and the other from the vagus nerve. Both ganglioneuromas were surgically removed, but the affected nerves had to be sacrificed. Postoperatively, the patient exhibited hypoglossal nerve and vocal fold palsy, but she was asymptomatic. In addition to the case description, we discuss the difficulties we faced during surgical excision.

  3. Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

    PubMed

    Kajimura, Daisuke; Paone, Riccardo; Mann, J John; Karsenty, Gerard

    2014-10-01

    The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1 Dbh-/- mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual. PMID:25353004

  4. Sympathetic neural control of indoleamine metabolism in the rat pineal gland

    NASA Technical Reports Server (NTRS)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

    1975-01-01

    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  5. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

    PubMed Central

    Levine, Benjamin D; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Zuckerman, Julie H; Diedrich, André; Biaggioni, Italo; Ray, Chester A; Smith, Michael L; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Mano, Tadaaki; Zhang, Rong; Iwasaki, Kenichi; Lane, Lynda D; Buckey, Jay C; Cooke, William H; Baisch, Friedhelm J; Robertson, David; Eckberg, Dwain L; Blomqvist, C Gunnar

    2002-01-01

    Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts ∼72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (± s.e.m.) stroke volume was lower (46 ± 5 vs. 76 ± 3 ml, P = 0.017) and heart rate was higher (93 ± 1 vs. 74 ± 4 beats min−1, P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 ± 256 vs. 1372 ± 62 dynes s cm−5, P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 ± 4 vs. 17 ± 2 bursts min−1, P = 0.04) and tilted (46 ± 4 vs. 38 ± 3 bursts min−1, P = 0.01) positions. A strong (r2 = 0.91–1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal. PMID:11773340

  6. [Morphometry of the adrenals].

    PubMed

    Chumachenko, P A

    1977-05-01

    The authors report on the method of determination of the weight indices of the adrenyl gland glomerular, testicular-reticular and medullar zones with a spheroid shape; it is substantiated by mathematical analysis of a plasticine model of the adrenal gland, whose characteristics approached the actual ones. The method was particularly accurate in determination of the weight of the fascicular-reticular and glomerular zones, and less--in determination of the weight of the medullary layer, the method's error being 0.6-0.9% in the first case, 2.7-3.5% in the second and 5.3-6.4 in the last. PMID:884280

  7. Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

    SciTech Connect

    Kirby, M.; Stewart, D.

    1984-11-01

    Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of (/sup 3/H)-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in (/sup 3/H)-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of (/sup 3/H)-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine.

  8. 5-HT1A receptors of the nucleus tractus solitarii facilitate sympathetic recovery following hypotensive hemorrhage in rats

    PubMed Central

    Vantrease, Jaime E.; Dudek, Nichole; DonCarlos, Lydia L.

    2015-01-01

    The role of serotonin in the hemodynamic response to blood loss remains controversial. Caudal raphe serotonin neurons are activated during hypotensive hemorrhage, and their destruction attenuates sympathetic increases following blood loss in unanesthetized rats. Caudal raphe neurons provide serotonin-positive projections to the nucleus tractus solitarii (NTS), and disruption of serotonin-positive nerve terminals in the NTS attenuates sympathetic recovery following hemorrhage. Administration of 5-HT1A-receptor agonists following hemorrhage augments sympathetic-mediated increases in venous tone and tissue hypoxia. These findings led us to hypothesize that severe blood loss promotes activation of 5-HT1A receptors in the NTS, which facilitates sympathetic recovery and peripheral tissue perfusion. Here, we developed an adeno-associated viral vector encoding an efficacious small hairpin RNA sequence targeting the rat 5-HT1A receptor. Unanesthetized rats subjected to NTS injection of the anti-rat 5-HT1A small hairpin RNA-encoding vector 4 wk prior showed normal blood pressure recovery, but an attenuated recovery of renal sympathetic nerve activity (−6.4 ± 12.9 vs. 42.6 ± 15.6% baseline, P < 0.05) 50 min after 21% estimated blood volume withdrawal. The same rats developed increased tissue hypoxia after hemorrhage, as indicated by prolonged elevations in lactate (2.77 ± 0.5 vs. 1.34 ± 0.2 mmol/l, 60 min after start of hemorrhage, P < 0.05). 5-HT1A mRNA levels in the commissural NTS were directly correlated with renal sympathetic nerve activity (P < 0.01) and inversely correlated with lactate (P < 0.05) 60 min after start of hemorrhage. The data suggest that 5-HT1A receptors in the commissural NTS facilitate tissue perfusion after blood loss likely by increasing sympathetic-mediated venous return. PMID:25980022

  9. Tension neuropathy of the superficial peroneal nerve: associated conditions and results of release.

    PubMed

    Johnston, E C; Howell, S J

    1999-09-01

    We reviewed eight patients who sustained superficial peroneal nerve neuralgia after an inversion ankle sprain. Surgical exploration found anatomic abnormalities that tethered the nerve from movement during plantarflexion and inversion of the ankle. Most patients' pain improved dramatically after release and anterior transposition of the nerve. Seven joints also underwent arthroscopy, which showed intra-articular disease that was consistent with the original trauma. Five patients had reflex sympathetic dystrophy, three of which resolved after nerve release. Nerve conduction studies were not helpful. Careful physical examination and local nerve blocks were most important in making the diagnosis and prescribing treatment. All conservative measures should be exhausted before surgery is considered.

  10. Sympathetic activity during passive heat stress in healthy aged humans

    PubMed Central

    Gagnon, Daniel; Schlader, Zachary J; Crandall, Craig G

    2015-01-01

    Abstract Cardiovascular adjustments during heat stress are generally attenuated in healthy aged humans, which could be due to lower increases in sympathetic activity compared to the young. We compared muscle sympathetic nerve activity (MSNA) between 11 young (Y: 28 ± 4 years) and 10 aged (A: 70 ± 5 years) subjects prior to and during passive heating. Furthermore, MSNA responses were compared when a cold pressor test (CPT) and lower body negative pressure (LBNP) were superimposed upon heating. Baseline MSNA burst frequency (Y: 15 ± 4 vs. A: 31 ± 3 bursts min−1, P ≤ 0.01) and burst incidence (Y: 26 ± 8 vs. A: 50 ± 7 bursts (100 cardiac cycles (CC))−1, P ≤ 0.01) were greater in the aged. Heat stress increased core temperature to a similar extent in both groups (Y: +1.2 ± 0.1 vs. A: +1.2 ± 0.0°C, P = 0.99). Absolute levels of MSNA remained greater in the aged during heat stress (burst frequency: Y: 47 ± 6 vs. A: 63 ± 11 bursts min−1, P ≤ 0.01; burst incidence: Y: 48 ± 8 vs. A: 67 ± 9 bursts (100 CC)−1, P ≤ 0.01); however, the increase in both variables was similar between groups (both P ≥ 0.1). The CPT and LBNP further increased MSNA burst frequency and burst incidence, although the magnitude of increase was similar between groups (both P ≥ 0.07). These results suggest that increases in sympathetic activity during heat stress are not attenuated in healthy aged humans. Key points Cardiovascular adjustments to heat stress are attenuated in healthy aged individuals, which could contribute to their greater prevalence of heat-related illnesses and deaths during heat waves. The attenuated cardiovascular adjustments in the aged could be due to lower increases in sympathetic nerve activity during heat stress. We examined muscle sympathetic nerve activity (MSNA) and plasma catecholamine concentrations in healthy young and aged individuals during whole-body passive heat stress. The main finding

  11. Adrenal hemangioma: a case report.

    PubMed

    Auh, Y H; Anand, J; Zirinsky, K; Kazam, E

    1986-01-01

    Adrenal hemangioma is a very rare tumor. Presented is the 18th case proved by autopsy or surgery reported in world literature. The tumor was incidentally discovered at autopsy. Unless this tumor has characteristic calcifications, phlebolith or phlebolithlike, its computed tomography appearance is nonspecific. Therefore, by computed tomography this tumor cannot be differentiated from other primary or secondary adrenal tumors. PMID:3943357

  12. Leiomyosarcoma of the adrenal vein.

    PubMed

    Shao, I-Hung; Lee, Wei-Chen; Chen, Tai-Di; Chiang, Yang-Jen

    2012-01-01

    Leiomyosarcoma of the adrenal gland is extremely rare in the literature. We present a patient with an adrenal leiomyosarcoma originating from the adrenal vein, the pathologic findings and management. A 66-year-old man who was a hepatitis B virus carrier was found to have a huge left suprarenal mass on sonography and computed axial tomography. A huge tumor in the left suprarenal area with a markedly engorged adrenal vein was found during an adrenalectomy. The tumor thrombus extended into the renal vein, close to the inferior vena cava. The left adrenal gland with the whole tumor thrombus was removed completely. Microscopically, the adrenal gland was compressed but not invaded by the spindle cell tumor, which was composed of interlacing fascicles of neoplastic smooth muscle cells. The tumor was localized within the adrenal vein and arose from the venous wall. The patient had no local recurrence for 18 months after en bloc excision of the tumor. We suggest that en bloc excision with a clear and adequate surgical margin is the most important cure procedure for adrenal leiomyosarcoma.

  13. Subfornical organ mediates sympathetic and hemodynamic responses to blood-borne proinflammatory cytokines.

    PubMed

    Wei, Shun-Guang; Zhang, Zhi-Hua; Beltz, Terry G; Yu, Yang; Johnson, Alan Kim; Felder, Robert B

    2013-07-01

    Proinflammatory cytokines play an important role in regulating autonomic and cardiovascular function in hypertension and heart failure. Peripherally administered proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), act on the brain to increase blood pressure, heart rate, and sympathetic nerve activity. These molecules are too large to penetrate the blood-brain barrier, and so the mechanisms by which they elicit these responses remain unknown. We tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ that lacks a blood-brain barrier, plays a major role in mediating the sympathetic and hemodynamic responses to circulating proinflammatory cytokines. Intracarotid artery injection of TNF-α (200 ng) or IL-1β (200 ng) dramatically increased mean blood pressure, heart rate, and renal sympathetic nerve activity in rats with sham lesions of the SFO (SFO-s). These excitatory responses to intracarotid artery TNF-α and IL-1β were significantly attenuated in SFO-lesioned (SFO-x) rats. Similarly, the increases in mean blood pressure, heart rate, and renal sympathetic nerve activity in response to intravenous injections of TNF-α (500 ng) or IL-1β (500 ng) in SFO-s rats were significantly reduced in the SFO-x rats. Immunofluorescent staining revealed a dense distribution of the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, in the SFO. These data suggest that SFO is a predominant site in the brain at which circulating proinflammatory cytokines act to elicit cardiovascular and sympathetic responses.

  14. Primary bilateral adrenal non-Hodgkin's lymphoma associated with normal adrenal function.

    PubMed

    Gu, Bin; Ding, Qiang; Xia, Guowei; Fang, Zujun; Fang, Jie; Jiang, Haowen; Yao, Mengshu

    2009-04-01

    Primary bilateral adrenal non-Hodgkin's lymphoma is rare. Adrenal insufficiency or adrenal failure as a result of tumor destruction is the main pathophysiological change of most cases. Normal adrenal function despite bulky bilateral adrenal masses is extremely rare. We present a case of primary bilateral adrenal non-Hodgkin's lymphoma associated with normal adrenal function. Positron emission tomography-computed tomography is helpful to the diagnosis.

  15. Methodological Standardization for the Preclinical Evaluation of Renal Sympathetic Denervation

    PubMed Central

    Sakakura, Kenichi; Ladich, Elena; Edelman, Elazer R.; Markham, Peter; Stanley, James R.L.; Keating, John; Kolodgie, Frank D.; Virmani, Renu; Joner, Michael

    2015-01-01

    Transcatheter ablation of renal autonomic nerves is a viable option for the treatment of resistent arterial hypertension; however, structured preclinical evaluation with standardization of analytical procedures remains a clear gap in this field. Here we discuss the topics relevant to the preclinical model for the evaluation of renal denervation (RDN) devices and report methodologies and criteria towards standardization of the safety and efficacy assessment, including histopathological evaluations of the renal artery, peri-arterial nerves, and associated peri-adventitial tissues. The preclinical swine renal artery model can be used effectively to assess both the safety and efficacy of RDN technologies. Assessment of the efficacy of RDN modalities primarily focuses on the determination of the depth of penetration of treatment-related injury (eg, necrosis) of the peri-arterial tissues and its relationship (ie, location and distance) and affect on the associated renal nerves and the correlation thereof with proxy biomarkers including renal norepinephrine concentrations and nerve-specific immunohistochemical stains (eg, tyrosine hydroxylase). The safety evaluation of RDN technologies involves assessing for adverse effects on tissues local to the site of treatment (ie, on the arterial wall) as well as tissues at a distance (eg, soft tissue, veins, arterial branches, skeletal muscle, adrenal gland, ureters). Increasing experience will help to create a standardized means of examining all arterial beds subject to ablative energy and in doing so enable us to proceed to optimize development and assessment of these emerging technologies. PMID:25240550

  16. Giant adrenal cyst: case study

    PubMed Central

    Carsote, M; Chirita, P; Terzea, D; Paun, S; Beuran, M

    2010-01-01

    One of the rarest situations regarding an adrenal incidentaloma is an adrenal cyst. We present the case of a 61Z–year old male patient diagnosed with peritonitis. During surgery, a right adrenal tumor of 2 cm is discovered. The patient was referred to endocrinology. 6 months later the diameter of the tumor is 7 times bigger than the initial stage. It has no secretory phenotype, except for the small increase of serum aldosterone and the 24–h 17–ketosteroids. Open right adrenalectomy is performed and a cyst of 15 cm is removed. The evolution after surgery is good. The pathological exam reveals an adrenal cyst with calcifications and osteoid metaplasia. The immunohistochemistry showed a positive reaction for CD34 and ACT in the vessels and VIM in the stroma. The adrenal cysts are not frequent and represent a challenge regarding the preoperative diagnostic and surgical procedure of resection. The pathological exam highlights the major aspects. PMID:20945822

  17. Radionuclide imaging of cardiac sympathetic innervation in heart failure: unlocking untapped potential.

    PubMed

    Gupta, Shuchita; Amanullah, Aman

    2015-03-01

    Heart failure (HF) is associated with sympathetic overactivity, which contributes to disease progression and arrhythmia development. Cardiac sympathetic innervation imaging can be performed using radiotracers that are taken up in the presynaptic nerve terminal of sympathetic nerves. The commonly used radiotracers are (123)I-metaiodobenzylguanidine ((123)I-mIBG) for planar and single-photon emission computed tomography imaging, and (11)C-hydroxyephedrine for positron emission tomography imaging. Sympathetic innervation imaging has been used in assessing prognosis, response to treatment, risk of ventricular arrhythmias and sudden death and prediction of response to cardiac resynchronization therapy in patients with HF. Other potential applications of these techniques are in patients with chemotherapy-induced cardiomyopathy, predicting myocardial recovery in patients with left ventricular assist devices, and assessing reinnervation following cardiac transplantation. There is a lack of standardization with respect to technique of (123)I-mIBG imaging that needs to be overcome for the imaging modality to gain popularity in clinical practice.

  18. Adrenal Development in Mice Requires GATA4 and GATA6 Transcription Factors.

    PubMed

    Tevosian, Sergei G; Jiménez, Elizabeth; Hatch, Heather M; Jiang, Tianyu; Morse, Deborah A; Fox, Shawna C; Padua, Maria B

    2015-07-01

    The adrenal glands consist of an outer cortex and an inner medulla, and their primary purposes include hormone synthesis and secretion. The adrenal cortex produces a complex array of steroid hormones, whereas the medulla is part of the sympathetic nervous system and produces the catecholamines epinephrine and norepinephrine. In the mouse, GATA binding protein (GATA) 4 and GATA6 transcription factors are coexpressed in several embryonic tissues, including the adrenal cortex. To explore the roles of GATA4 and GATA6 in mouse adrenal development, we conditionally deleted these genes in adrenocortical cells using the Sf1Cre strain of animals. We report here that mice with Sf1Cre-mediated double deletion of Gata4 and Gata6 genes lack identifiable adrenal glands, steroidogenic factor 1-positive cortical cells and steroidogenic gene expression in the adrenal location. The inactivation of the Gata6 gene alone (Sf1Cre;Gata6(flox/flox)) drastically reduced the adrenal size and corticosterone production in the adult animals. Adrenocortical aplasia is expected to result in the demise of the animal within 2 weeks after birth unless glucocorticoids are provided. In accordance, Sf1Cre;Gata4(flox/flox)Gata6(flox/flox) females depend on steroid supplementation to survive after weaning. Surprisingly, Sf1Cre;Gata4(flox/flox)Gata6(flox/flox) males appear to live normal lifespans as vital steroidogenic synthesis shifts to their testes. Our results reveal a requirement for GATA factors in adrenal development and provide a novel tool to characterize the transcriptional network controlling adrenocortical cell fates.

  19. Adrenal Development in Mice Requires GATA4 and GATA6 Transcription Factors

    PubMed Central

    Jiménez, Elizabeth; Hatch, Heather M.; Jiang, Tianyu; Morse, Deborah A.; Fox, Shawna C.

    2015-01-01

    The adrenal glands consist of an outer cortex and an inner medulla, and their primary purposes include hormone synthesis and secretion. The adrenal cortex produces a complex array of steroid hormones, whereas the medulla is part of the sympathetic nervous system and produces the catecholamines epinephrine and norepinephrine. In the mouse, GATA binding protein (GATA) 4 and GATA6 transcription factors are coexpressed in several embryonic tissues, including the adrenal cortex. To explore the roles of GATA4 and GATA6 in mouse adrenal development, we conditionally deleted these genes in adrenocortical cells using the Sf1Cre strain of animals. We report here that mice with Sf1Cre-mediated double deletion of Gata4 and Gata6 genes lack identifiable adrenal glands, steroidogenic factor 1-positive cortical cells and steroidogenic gene expression in the adrenal location. The inactivation of the Gata6 gene alone (Sf1Cre;Gata6flox/flox) drastically reduced the adrenal size and corticosterone production in the adult animals. Adrenocortical aplasia is expected to result in the demise of the animal within 2 weeks after birth unless glucocorticoids are provided. In accordance, Sf1Cre;Gata4flox/floxGata6flox/flox females depend on steroid supplementation to survive after weaning. Surprisingly, Sf1Cre;Gata4flox/floxGata6flox/flox males appear to live normal lifespans as vital steroidogenic synthesis shifts to their testes. Our results reveal a requirement for GATA factors in adrenal development and provide a novel tool to characterize the transcriptional network controlling adrenocortical cell fates. PMID:25933105

  20. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

    PubMed

    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.

  1. Tonic arterial chemoreceptor activity contributes to cardiac sympathetic activation in mild ovine heart failure.

    PubMed

    Xing, Daniel T; May, Clive N; Booth, Lindsea C; Ramchandra, Rohit

    2014-08-01

    Heart failure (HF) is associated with a large increase in cardiac sympathetic nerve activity (CSNA), which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is increasing evidence that arterial chemoreceptor activation plays an important role in stimulating renal sympathetic nerve activity (RSNA) and muscle sympathetic nerve activity in HF. Given that sympathetic nerve activity to individual organs is differentially controlled, we investigated whether tonic arterial chemoreceptor activation contributes to the increased CSNA in HF. We recorded CSNA and RSNA in conscious normal sheep and in sheep with mild HF induced by rapid ventricular pacing (ejection fraction <40%). Tonic arterial chemoreceptor function was evaluated by supplementing room air with 100% intranasal oxygen (2-3 l min(-1)) for 20 min, thereby deactivating chemoreceptors. The effects of hyperoxia on resting levels and baroreflex control of heart rate, CSNA and RSNA were determined. In HF, chemoreceptor deactivation induced by hyperoxia significantly reduced CSNA [90 ± 2 versus 75 ± 5 bursts (100 heart beats)(-1), P < 0.05, n = 10; room air versus hyperoxia] and heart rate (96 ± 4 versus 85 ± 4 beats min(-1), P < 0.001, n = 12). There was no change in RSNA burst incidence [93 ± 4 versus 92 ± 4 bursts (100 heart beats)(-1), n = 7], although due to the bradycardia the RSNA burst frequency was decreased (90 ± 8 versus 77 ± 7 bursts min(-1), P < 0.001). In normal sheep, chemoreceptor deactivation reduced heart rate without a significant effect on CSNA or RSNA. In summary, deactivation of peripheral chemoreceptors during HF reduced the elevated levels of CSNA, indicating that tonic arterial chemoreceptor activation plays a critical role in stimulating the elevated CSNA in HF.

  2. The effects of vasoactive intestinal peptide on adrenal steroid hormone secretion

    SciTech Connect

    Cunningham, L.A.

    1988-01-01

    Vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers have been demonstrated in the rat adrenal cortex in close association with zona glomerulosa cells. We have studied the effects of VIP on steroid hormone secretion from the outer zones of the normal rat adrenal cortex. Intact capsule-glomerulosa preparations, consisting of the capsule, zona glomerulosa, and a small portion of the zona fasciculata were perifused in vitro. The secretory responsiveness was assessed by measuring aldosterone and corticosterone release following stimulation with the physiological secretagogues ACTH and angiotensin II. The distribution of adrenal VIP receptors was assessed by in vitro autoradiography of {sup 125}I-VIP binding. {sup 125}I-VIP (0.75 and 2.0 nM) binding was concentrated in the capsule and zone glomerulosa, coincident with the distribution of VIP nerve fibers which aborize extensively in this region. The specificity of this binding was demonstrated using unlabelled VIP, ACTH and angiotensin II.

  3. Solitary neurofibroma of the adrenal gland not associated with type-1 neurofibromatosis

    PubMed Central

    Gupta, Pallav; Aggarwal, Riti; Sarangi, Rathindra

    2015-01-01

    Neurofibromas are tumors of neural origin. They can be solitary or may be associated with neurofibromatosis type-1 (NF-1). These are mostly seen in the head and neck region, upper extremities or along the nerves. Visceral neurofibromas are extremely rare. In this paper, we present an unusual case of solitary neurofibroma of the adrenal gland not associated with NF-1. PMID:25657564

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

    PubMed

    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. T