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Sample records for single rat sympathetic

  1. 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

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

    PubMed Central

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

    2012-01-01

    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

  3. Chronically lowering sympathetic activity protects sympathetic nerves in spleens from aging F344 rats

    PubMed Central

    Perez, Sam D.; Kozic, Brooke; Molinaro, Christine; Thyagarajan, Srinivasan; Ghamsary, Mark; Lubahn, Cheri L.; Lorton, Dianne; Bellinger, Denise L.

    2013-01-01

    In the present study, we investigated how increased sympathetic tone during middle-age affects the splenic sympathetic neurotransmission. Fifteen-month-old F344 rats received rilmenidine (0, 0.5 or 1.5 mg/kg/day, i.p. for 90 days) to lower sympathetic tone. Controls for age were untreated 3 or 18M rats. We report that rilmenidine (1) reduced plasma and splenic norepinephrine concentrations and splenic norepinephrine turnover, and partially reversed the sympathetic nerve loss; and (2) increased β-adrenergic receptor (β-AR) density and β-AR-stimulated cAMP production. Collectively, these findings suggest a protective effect of lowering sympathetic tone on sympathetic nerve integrity, and enhanced sympathetic neurotransmission in secondary immune organs. PMID:22546498

  4. Longitudinal Evaluation of Sympathetic Nervous System and Perfusion in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic Single-Photon Emission Computed Tomography.

    PubMed

    Zan, Yunlong; Boutchko, Rostyslav; Huang, Qiu; Li, Biao; Chen, Kewei; Gullberg, Grant T

    2015-01-01

    The objective of this work was to evaluate the sympathetic nervous system and structure remodeling during the progression of heart failure in a rodent model using dynamic cardiac single-photon emission computed tomography (SPECT). The spontaneously hypertensive rat (SHR) model was used to study changes in the nervous system innervation and perfusion in the left ventricular (LV) myocardium with the progression of left ventricular hypertrophy (LVH) to heart failure. Longitudinal dynamic SPECT studies were performed with seven SHR and seven Wistar-Kyoto (WKY) rats over 1.5 years using a dual-head SPECT scanner with pinhole collimators. Time-activity curves (TACs) of the 123I-MIBG and 201Tl distribution in the LV blood pool and myocardium were extracted from dynamic SPECT data and fitted to compartment models to determine the influx rate, washout rate, and distribution volume (DV) of 123I-MIBG and 201Tl in the LV myocardium. The standardized uptake values (SUVs) of 123I-MIBG and 201Tl in the LV myocardium were also calculated from the static reconstructed images. The influx and washout rates of 123I-MIBG did not show a significant difference between SHRs and WKY rats. The DVs of 123I-MIBG were greater in the SHRs than in the WKY rats (p = .0028). Specifically, the DV of 123I-MIBG became greater in the SHRs by 6 months of age (p = .0017) and was still significant at the age of 22 months. The SUV of 123I-MIBG in SHRs exhibited abnormal values compared to WKY rats from the age of 18 months. There was no difference in the influx rate and the washout rate of 201Tl between the SHRs and WKY rats. The SHRs exhibited greater DV of 201Tl than WKY rats after the age of 18 months (p = .034). The SUV of 201Tl in SHRs did not show any significant difference from WKY at all ages. The higher DV of 123I-MIBG in the LV myocardium reveals abnormal nervous system activity of the SHRs at an age of 6 months, whereas a greater DV of 201Tl in the LV myocardium can only be detected at an age

  5. 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

  6. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats.

    PubMed

    Shimojo, G L; Palma, R K; Brito, J O; Sanches, I C; Irigoyen, M C; De Angelis, K

    2015-06-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation. PMID:25831206

  7. Specialised sympathetic neuroeffector associations in rat iris arterioles

    PubMed Central

    SANDOW, SHAUN L.; WHITEHOUSE, DREW; HILL, CARYL E.

    1998-01-01

    Vascular sympathetic neuroeffector associations have been examined in rat iris arterioles using serial section electron microscopy and reconstruction techniques. Examination of random sections showed that, of all profiles of varicosities (199) seen to lie closer than 4 μm to vascular smooth muscle cells, only a small proportion (29/199) were found in close association with vascular smooth muscle cells, where adjacent membranes were separated by less than 100 nm. However, serial section examination, from intervaricose region to intervaricose region, of 79 varicosities similarly observed lying within 4 μm of vascular smooth muscle cells showed that 54 formed close associations with vascular smooth muscle cells. In serial sections, all these varicosities were also closely associated with melanocytes and of the 25 remaining varicosities, 22 formed close associations with melanocytes alone, whilst 3 did not come into close association with any effector cell. The increased observation of close associations with vascular smooth muscle cells in serial sections, compared with random sections, is consistent with the demonstration that the area of contact only occupies, on average, a small percentage (5%) of the total surface area of the varicosity as seen in the 3-dimensional reconstructions. In both random and serial sections, close associations were observed between varicosities and vascular smooth muscle cells or melanocytes irrespective of whether fibres were present singly or in small nerve bundles. Three-dimensional reconstruction of associations of varicosities and vascular smooth muscle cells demonstrated several common features, such as accumulations of synaptic vesicles and loss of Schwann cell covering at the region of membrane facing the effector cell. The similarity in the appearance of the neuroeffector association seen in this study and those described in previous studies provides evidence for the existence of a common sympathetic neuroeffector association

  8. Differential Sympathetic Vasomotor Activation Induced by Liver Cirrhosis in Rats

    PubMed Central

    Bergamaschi, Cássia T.; Campos, Ruy R.

    2016-01-01

    We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase. PMID:27055088

  9. Sympathetic activation in rats with L-NAME-induced hypertension.

    PubMed

    Biancardi, V C; Bergamaschi, C T; Lopes, O U; Campos, R R

    2007-03-01

    We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/- SEM) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension. PMID:17334538

  10. Plasma Catecholamines (CA) and Gene Expression of CA Biosynthetic Enzymes in Adrenal Medulla and Sympathetic Ganglia of Rats Exposed to Single or Repeated Hypergravity

    NASA Astrophysics Data System (ADS)

    Petrak, J.; Jurani, M.; Baranovska, M.; Hapala, I.; Frollo, I.; Kvetnansky, R.

    2008-06-01

    The aim of this study was to evaluate plasma epinephrine (EPI) and norepinephrine (NE) levels in blood collected directly during a single or 8-times repeated centrifugation at hypergravity 4G, using remote controlled equipment. Plasma EPI levels showed a huge hypergravity-induced increase. After the last blood collection during hypergravity, the centrifuge was turned off and another blood sampling was performed immediately after the centrifuge decelerated and stopped (10 min). In these samples plasma EPI showed significantly lower levels compared to centrifugation intervals. Plasma NE levels showed none or small changes. Repeated exposure to hypergravity 4G (8 days for 60 min) eliminated the increase in plasma EPI levels at the 15 min interval but did not markedly affect plasma NE levels. To explain these findings we measured mRNA levels of CA biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla (AM) and stellate ganglia (SG) of rats exposed to continuous hypergravity (2G) up to 6 days. In AM, TH, DBH and PNMT mRNA levels were significantly increased in intervals up to 3 days, however, after 6 day hypergravity exposure, no significant elevation was found. In SG, no significant changes in gene expression of CA enzymes were seen both after a single or repeated hypergravity. Thus, our data show that hypergravity highly activates the adrenomedullary system, whereas the sympathoneural system is not significantly changed. In conclusion, our results demonstrate that during repeated or continuous exposure of the organism to hypergravity the adrenomedullary system is adapted, whereas sympathoneural system is not affected.

  11. Outward currents in voltage-clamped rat sympathetic neurones.

    PubMed Central

    Galvan, M; Sedlmeir, C

    1984-01-01

    Outward membrane currents were studied in neurones of the isolated rat superior cervical ganglion by using a two-micro-electrode or single-micro-electrode voltage-clamp technique. Under current clamp, depolarization elicited electrotonic potentials that displayed marked outward rectification. From negative resting potentials (-70 mV) a short latency, short duration outward rectification was observed. From more positive potentials (-40 mV) a longer latency persistent outward rectification could be demonstrated. Under voltage clamp, four distinct outward currents were observed: a delayed rectifier (IK); a transient outward current (IA); a Ca2+-activated current (IC) and the M-current (IM). The maximum amplitude of IK, IA and IC was 1-2 orders of magnitude greater than IM. Depolarizing from -40 mV to potentials more positive than -20 mV co-activated IK and IC, producing a characteristic N-shaped current voltage curve with a minimum at about +80 mV. Superfusion with Mn2+-containing solutions reduced outward current at all voltages and abolished the N-characteristic; the remaining current (IK) slowly inactivated (tau greater than 1 s). Raising [K+]o from 6 to 36 mmol/l reversed outward tail currents observed in normal solution. Addition of tetraethylammonium ions (1-3 mmol/l) strongly reduced the amplitude of IK and IC. IA was characterized by very rapid activation at potentials more positive than -60 mV and by fast and complete inactivation at potentials in the activation range. The amplitude of IA was dependent on [K+]o and was reduced by external 4-aminopyridine (1-3 mmol/l). The activation appeared to depend on the nature and concentration of divalent cations present in the superfusate. It is concluded that the soma membrane of rat sympathetic neurones, like many other vertebrate and invertebrate neurones, contains multiple populations of K+ channels. The possible functions of these in the control of ganglion cell excitability are discussed. PMID:6097667

  12. 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.

  13. Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats.

    PubMed

    da Silva Mattos, Alexandro Márcio; Xavier, Carlos Henrique; Karlen-Amarante, Marlusa; da Cunha, Natália Veronez; Fontes, Marco Antonio Peliky; Martins-Pinge, Marli Cardoso

    2012-08-01

    The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity. PMID:22705582

  14. Influence of cervical sympathetic nerves on ventilation and upper airway resistance in the rat.

    PubMed

    O'Halloran, K D; Curran, A K; Bradford, A

    1998-07-01

    The cervical sympathetic trunks innervate the carotid bodies, carotid baroreceptors, thyroid gland and the upper airway mucosa, structures which can influence breathing and upper airway resistance. However, their role in the control of ventilation and upper airway patency is poorly understood. A constant airflow was applied to the upper airway through a high-cervical tracheostomy in anaesthetized rats breathing spontaneously through a low-cervical tracheostomy. The peripheral ends of the cut cervical sympathetic trunks were stimulated electrically and airflow resistance and ventilation were measured. The effects of cervical sympathetic trunk section on ventilation were also measured in conscious rats. In conscious rats, cutting the sympathetic trunks caused a decrease in ventilation during normoxia but only slightly affected ventilatory responses to hypoxia and hypercapnia. In anaesthetized rats, sympathetic trunk stimulation caused an inhibition of breathing which was sometimes followed by excitation. These responses were unaffected by alpha- or beta-adrenoceptor blockade but were abolished by cutting the carotid sinus nerves. Sympathetic stimulation also caused a fall in upper airway resistance which was reduced by bypassing the nose, unaffected by propranolol or carotid sinus nerve section and abolished by phentolamine. It was concluded that the cervical sympathetic nerves exert important influences on ventilation and upper airway resistance. PMID:9701434

  15. Sympathetic Hyperinnervation and Inflammatory Cell NGF Synthesis Following Myocardial Infarction in Rats

    PubMed Central

    Hasan, Wohaib; Jama, Abdi; Donohue, Timothy; Wernli, Gwenaelle; Onyszchuk, Gregory; Al-Hafez, Baraa; Bilgen, Mehmet; Smith, Peter G.

    2006-01-01

    Sympathetic hyperinnervation occurs in human ventricular tissue after myocardial infarction and may contribute to arrhythmias. Aberrant sympathetic sprouting is associated with elevated nerve growth factor (NGF) in many contexts, including ventricular hyperinnervation. However, it is unclear whether cardiomyocytes or other cell types are responsible for increased NGF synthesis. In this study, left coronary arteries were ligated and ventricular tissue examined in rats 1-28 days post-infarction. Infarct and peri-infarct tissue was essentially devoid of sensory and parasympathetic nerves at all time points. However, areas of increased sympathetic nerve density were observed in the peri-infarct zone between post-ligation days 4-14. Hyperinnervation occurred in regions containing accumulations of macrophages and myofibroblasts. To assess whether these inflammatory cells synthesize NGF, sections were processed for NGF in situ hybridization and immunohistochemistry. Both macrophage1 antigen-positive macrophages and α-smooth muscle actin immunoreactive myofibroblasts expressed NGF in areas where they were closely proximate to sympathetic nerves. To investigate whether NGF produced by peri-infarct cells induces sympathetic outgrowth, we co-cultured adult sympathetic ganglia with peri-infarct explants. Neurite outgrowth from sympathetic ganglia was significantly greater at post-ligation days 7-14 as compared to control tissue. Addition of an NGF function-blocking antibody prevented the increased neurite outgrowth induced by peri-infarct tissue. These findings provide evidence that inflammatory cell NGF synthesis plays a causal role in sympathetic hyperinnervation following myocardial infarction. Section: Disease-Related Neuroscience PMID:17084822

  16. Effect of experimental hyperinsulinemia on sympathetic nervous system activity in the rat

    SciTech Connect

    Young, J.B.

    1988-01-01

    Since insulin acutely stimulates the sympathetic nervous system, a role for sympathetic overactivity has been hypothesized to underlie the association between chronic hyperinsulinemia and hypertension. To assess the effect of sustained hyperinsulinemia on sympathetic function, (/sup 3/H)norepinephrine (NE) turnover was measured in rats injected with insulin for 14d. NE turnover in insulin-treated animals given free access to lab chow and a 10% sucrose solution was compared with that obtained in rats fed chow alone or chow plus sucrose. Sucrose ingestion increased NE turnover in heart, brown adipose tissue, and liver, but exogenous insulin did not augment turnover beyond that seen in animals given sucrose alone. This study, therefore, provides no evidence that chronic hyperinsulinemia, sufficient to induce peripheral insulin resistance, stimulates sympathetic activity more than that produced by chronic sucrose ingestion.

  17. Respiratory modulation of sympathetic nerve activity is enhanced in male rat offspring following uteroplacental insufficiency.

    PubMed

    Menuet, C; Wlodek, M E; Fong, A Y; Allen, A M

    2016-06-01

    Sympathetic nerve activity to the cardiovascular system displays prominent respiratory-related modulation which leads to the generation of rhythmic oscillations in blood pressure called Traube-Hering waves. An amplification of this respiratory modulation of sympathetic activity is observed in hypertension of both genetic, the spontaneously hypertensive rat, and induced, chronic intermittent hypoxia or maternal protein restriction during gestation, origin. Male offspring of mothers with uteroplacental insufficiency, induced by bilateral uterine vessel ligation at 18 days of gestation, are also hypertensive in adulthood. In this study we examined whether these male offspring display altered respiratory modulation of sympathetic activity at pre-hypertensive ages compared to controls. Respiratory, cardiovascular and sympathetic parameters were examined using the working heart-brainstem preparation in 35 day old male rats that had reduced birth weight due to uteroplacental insufficiency. Whilst all respiratory parameters were not different between groups, we observed an enhanced respiratory-related burst of thoracic sympathetic nerve activity and amplified Traube-Hering waves in the growth-restricted group. This group also showed an increased sympathetic and bradycardic response to activation of peripheral chemoreceptors. The observations add support to the view that altered respiratory modulation of sympathetic activity represents a common mechanism involved in the development of several forms of hypertension. PMID:26593642

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

    PubMed

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

    2005-06-01

    The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5-11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O(2))11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O(2))11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM. PMID:15731401

  19. Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation

    PubMed Central

    Kim, Woo-Yang; Gonsiorek, Eugene A.; Barnhart, Chris; Davare, Monika A.; Engebose, Abby J.; Lauridsen, Holly; Bruun, Donald; Lesiak, Adam; Wayman, Gary; Bucelli, Robert; Higgins, Dennis; Lein, Pamela J.

    2014-01-01

    Clinical and experimental evidence suggest that statins decrease sympathetic activity, but whether peripheral mechanisms involving direct actions on post-ganglionic sympathetic neurons contribute to this effect is not known. Because tonic activity of these neurons is directly correlated with the size of their dendritic arbor, we tested the hypothesis that statins decrease dendritic arborization in sympathetic neurons. Oral administration of atorvastatin (20 mg/kg/day for 7 days) significantly reduced dendritic arborization in vivo in sympathetic ganglia of adult male rats. In cultured sympathetic neurons, statins caused dendrite retraction and reversibly blocked bone morphogenetic protein-induced dendritic growth without altering cell survival or axonal growth. Supplementation with mevalonate or isoprenoids, but not cholesterol, attenuated the inhibitory effects of statins on dendritic growth, whereas specific inhibition of isoprenoid synthesis mimicked these statin effects. Statins blocked RhoA translocation to the membrane, an event that requires isoprenylation, and constitutively active RhoA reversed statin effects on dendrites. These observations that statins decrease dendritic arborization in sympathetic neurons by blocking RhoA activation suggest a novel mechanism by which statins decrease sympathetic activity and protect against cardiovascular and cerebrovascular disease. PMID:19209406

  20. GABA and enkephalin tonically alter sympathetic outflows in the rat spinal cord.

    PubMed

    Bowman, Belinda R; Goodchild, Ann K

    2015-12-01

    GABA and enkephalin provide significant innervation of sympathetic preganglionic neurons. Despite some investigation as to the identity of premotor sources of these innervations no comprehensive analyses have been conducted. Similarly, although data describing the cardiovascular effects of blockade of GABAA receptors in the spinal cord is available, the effects at other sympathetic outflows are unknown. In contrast the sympathetic effects of opioid blockade in the spinal cord are unclear. The aims of this study were to identify potential sympathetic premotor sources of GABAergic and enkephalinergic input to the spinal cord and to describe the sympathetic and cardiovascular effects of spinal GABAA receptor and delta/mu opioid receptor blockade in urethane anaesthetised rats. Glutamic acid decarboxylase (GAD67) and preproenkephalin (PPE) mRNA were found in all regions containing sympathetic premotor neurons, with the medullary raphe and RVMM providing the major GABAergic projections, while the PVN, RVMM and medullary raphe provided the major enkephalinergic projections. Intrathecal injection of bicuculline, a GABAA antagonist, elicited large and prolonged increases in all outflows measured, confirming previous work describing a tonic GABAergic influence on vasomotor tone, and revealing a tonic GABAergic inhibition of interscapular brown adipose tissue temperature. Intrathecal naloxone elicited transient small inhibitory effects only on MAP and HR. Thus GABA acting in the spinal cord plays an important role in the tonic suppression of sympathetic outflows while enkephalin appears to play only a minor role. PMID:26329875

  1. Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure

    PubMed Central

    Lu, Jian

    2014-01-01

    Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185

  2. Effects of anesthetics on the renal sympathetic response to anaphylactic hypotension in rats.

    PubMed

    Sun, Lingling; Tanida, Mamoru; Wang, Mofei; Kuda, Yuhichi; Kurata, Yasutaka; Shibamoto, Toshishige

    2014-01-01

    The autonomic nervous system plays an important role in rat anaphylactic hypotension. It is well known that sympathetic nerve activity and cardiovascular function are affected by anesthetics. However, the effects of different types of anesthesia on the efferent renal sympathetic nerve activity (RSNA) during anaphylactic hypotension remain unknown. Therefore, we determined the renal sympathetic responses to anaphylactic hypotension in anesthetized and conscious rats and the roles of baroreceptors in these responses. Sprague-Dawley rats were randomly allocated to anesthetic groups that were given pentobarbital, urethane, or ketamine-xylazine and to a conscious group. The rats were sensitized using subcutaneously injected ovalbumin. The systemic arterial pressure (SAP), RSNA and heart rate (HR) were measured. The effects of sinoaortic baroreceptor denervation on RSNA during anaphylaxis were determined in pentobarbital-anesthetized and conscious rats. In all of the sensitized rats, the RSNA increased and SAP decreased after antigen injection. At the early phase within 35 min of the antigen injection, the antigen-induced sympathoexcitation in the conscious rats was significantly greater than that in the anesthetized rats. Anaphylactic hypotension was attenuated in the conscious rats compared to the anesthetized rats. The anesthetic-induced suppression of SAP and RSNA was greater in the order ketamine-xylazine >urethane = pentobarbital. Indeed, in the rats treated with ketamine-xylazine, RSNA did not increase until 40 min, and SAP remained at low levels after the antigen injection. The baroreceptor reflex, as evaluated by increases in RSNA and HR in response to the decrease in SAP induced by sodium nitroprusside (SNP), was suppressed in the anesthetized rats compared with the conscious rats. Consistent with this finding, baroreceptor denervation attenuated the excitatory responses of RSNA to anaphylaxis in the conscious rats but not in the pentobarbital

  3. Modulation of the sympathetic response to acute hypoxia by the caudal ventrolateral medulla in rats

    PubMed Central

    Mandel, Daniel A; Schreihofer, Ann M

    2009-01-01

    Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. We examined the hypothesis that cardiovascular-related neurones in the caudal ventrolateral medulla (CVLM) contribute to the complex sympathetic response to hypoxia. In chloralose-anaesthetized, ventilated, vagotomized rats, acute hypoxia (10% O2, 60 s) evoked an increase in SNA (103 ± 12%) that was characterized by a decrease in activity during early inspiration followed by a prominent rise during expiration. Some recorded baro-activated CVLM neurones (n= 13) were activated by hypoxia, and most of these neurones displayed peak activity during inspiration that was enhanced during hypoxia. In contrast, other baro-activated CVLM neurones were inhibited during hypoxia (n= 6), and most of these neurones showed peak activity during expiration prior to the onset of hypoxia. Microinjection of the glutamate antagonist kynurenate into the CVLM eliminated the respiratory-related fluctuations in SNA during hypoxia and exaggerated the magnitude of the sympathetic response. In contrast, microinjection of a GABAA antagonist (bicuculline or gabazine) into the CVLM dramatically attenuated the sympathetic response to hypoxia. These data suggest the response to hypoxia in baro-activated CVLM neurones is related to their basal pattern of respiratory-related activity, and changes in the activity of these neurones is consistent with a contribution to the respiratory-related sympathetic responses to hypoxia. Furthermore, both glutamate and GABA in the CVLM contribute to the complex sympathetic response to acute hypoxia. PMID:19047207

  4. TRPA1 and Sympathetic Activation Contribute to Increased Risk of Triggered Cardiac Arrhythmias in Hypertensive Rats Exposed to Diesel Exhaust

    PubMed Central

    Haykal-Coates, Najwa; Winsett, Darrell W.; Krantz, Q. Todd; King, Charly; Costa, Daniel L.; Farraj, Aimen K.

    2011-01-01

    Background: Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias. Objective: We hypothesized that increased risk of triggered arrhythmias 1 day after DE exposure is mediated by airway sensory nerves bearing transient receptor potential (TRP) channels [e.g., transient receptor potential cation channel, member A1 (TRPA1)] that, when activated by noxious chemicals, can cause a centrally mediated autonomic imbalance and heightened risk of arrhythmia. Methods: Spontaneously hypertensive rats implanted with radiotelemeters were whole-body exposed to either 500 μg/m3 (high) or 150 μg/m3 (low) whole DE (wDE) or filtered DE (fDE), or to filtered air (controls), for 4 hr. Arrhythmogenesis was assessed 24 hr later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored. Results: Rats exposed to wDE or fDE had slightly higher HRs and increased low-frequency:high-frequency ratios (sympathetic modulation) than did controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than did controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE–exposed rats with a TRPA1 antagonist or sympathetic blockade prevented the heightened sensitivity to arrhythmia. Conclusions: These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. The gaseous components appear to play an important role in the proarrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants may partly exhibit their toxicity by lowering the threshold for secondary triggers, complicating assessment of their risk. PMID:21377951

  5. Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

    PubMed Central

    Muntzel, Martin S.

    2013-01-01

    The sympathetic nervous system plays a pivotal role in homeostasis through its direct innervation and functional impact on a variety of end organs. In rats, a number of methods are available to assess sympathetic nervous system function. Traditionally, direct recording of sympathetic nerve activity (SNA) has been restricted to acute, anesthetized preparations or conscious animals within a few days after electrode implantation. However, these approaches provide short-term data in studies designed to investigate changes in SNA during chronic disease states. Over the last several years, chronic SNA recording has been pioneered in rabbits and more recently in rats. The purpose of this article is to provide insights and a “how to” guide for chronic SNA recordings in rats based on experiences from two independent laboratories. We will present common methodologies used to chronically record SNA, characteristics and methods to distinguish sympathetic bursts versus electrical artifacts (and provide corresponding audio clips when available), and provide suggestions for analysis and presentation of data. In many instances, these same guidelines are applicable to acute SNA recordings. Using the surgical approaches described herein, both laboratories have been able to chronically record SNA in >50% of rats for a duration >3 wk. The ability to record SNA over the time course of several weeks will, undoubtedly, greatly impact the field of autonomic and cardiovascular physiology. PMID:24014674

  6. Neurophysiological assessment of sympathetic cardiovascular activity after loss of postganglionic neurons in the anesthetized rat.

    PubMed

    Zahner, Matthew R; Liu, Chang-Ning; Okerberg, Carlin V; Opsahl, Alan C; Bobrowski, Walter F; Somps, Chris J

    2016-01-01

    The goal of this study was to determine the degree of sympathetic postganglionic neuronal loss required to impair cardiovascular-related sympathetic activity. To produce neuronal loss separate groups of rats were treated daily with guanethidine for either 5days or 11days, followed by a recovery period. Sympathetic activity was measured by renal sympathetic nerve activity (RSNA). Stereology of thoracic (T13) ganglia was performed to determine neuronal loss. Despite loss of more than two thirds of neurons in T13 ganglia in both treated groups no effect on resting blood pressure (BP) or heart rate (HR) was detected. Basal RSNA in rats treated for 5days (0.61±0.10μV∗s) and 11days (0.37±0.08μV∗s) was significantly less than vehicle-treated rats (0.99±0.13μV∗s, p<0.05). Increases in RSNA by baroreceptor unloading were significantly lower in 5-day (1.09±0.19μV∗s) and 11-day treated rats (0.59±0.11μV∗s) compared with vehicle-treated rats (1.82±0.19μV∗s, p<0.05). Increases in RSNA to chemoreceptor stimulation were significantly lower in 5-day treated rats (1.54±0.25μV∗s) compared with vehicle-treated rats (2.69±0.23μV∗s, p<0.05). Increases in RSNA in 11-day treated rats were significantly lower (0.75±0.15μV∗s, p<0.05) compared with both vehicle-treated and 5-day treated rats. A positive correlation of neurons to sympathetic responsiveness but not basal activity was detected. These data suggest that diminished capacity for reflex sympathetic responsiveness rather than basal activity alone must be assessed for complete detection of neurophysiological cardiovascular impairment. PMID:27085835

  7. 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.

  8. Do the carotid body chemoreceptors mediate cardiovascular and sympathetic adjustments induced by sodium overload in rats?

    PubMed

    Pedrino, Gustavo R; Mourão, Aline A; Moreira, Marina C S; da Silva, Elaine F; Lopes, Paulo R; Fajemiroye, James O; Schoorlemmer, Guss H M; Sato, Mônica A; Reis, Ângela A S; Rebelo, Ana C S; Cravo, Sergio L

    2016-05-15

    Acute plasma hypernatremia induces several cardiovascular and sympathetic responses. It is conceivable that these responses contribute to rapid sodium excretion and restoration of normal conditions. Afferent pathways mediating these responses are not entirely understood. The present study analyses the effects of acute carotid chemoreceptor inactivation on cardiovascular and sympathetic responses induced by infusion of hypertonic saline (HS). All experiments were performed on anesthetized male Wistar rats instrumented for recording of arterial blood pressure (ABP), renal blood flow (RBF) and renal sympathetic nerve activity (RSNA). Animals were subjected to sham surgery or carotid chemoreceptor inactivation by bilateral ligation of the carotid body artery (CBA). In sham rats (n=8), intravenous infusion of HS (3 M NaCl, 1.8 ml/kg b.wt.) elicited a transient increase (9±2mmHg) in ABP, and long lasting (30 min) increases in RBF (138±5%) and renal vascular conductance (RVC) (128±5%) with concurrent decrease in RSNA (-19±4%). In rats submitted to CBA ligation (n=8), the pressor response to HS was higher (24±2mmHg; p<0.05). However, RBF and RVC responses to HS infusion were significantly reduced (113±5% and 93±4%, respectively) while RSNA was increased (13±2%). When HS (3M NaCl, 200μl) was administrated into internal carotid artery (ICA), distinct sympathetic and cardiovascular responses were observed. In sham-group, HS infusion (3M NaCl, 200μl) into ICA promoted an increase in ABP (26±8mmHg) and RSNA (29±13%). In CBA rats, ABP (-3±5.6mmHg) remained unaltered despite sympathoinhibition (-37.6±5.4%). These results demonstrate that carotid body chemoreceptors play a role in the development of hemodynamic and sympathetic responses to acute HS infusion. PMID:27060222

  9. 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.

  10. Nonselective Blocking of the Sympathetic Nervous System Decreases Detrusor Overactivity in Spontaneously Hypertensive Rats

    PubMed Central

    Kim, Khae-Hawn; Jin, Long-Hu; Choo, Gwoan-Youb; Lee, Hun-Jae; Choi, Bo-Hwa; Kwak, Jiyeon; Yoon, Sang-Min; Park, Chang-Shin; Lee, Tack

    2012-01-01

    The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min−1 to 0.28 ± 0.19 min−1 (p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H2O to 1.90 ± 0.86 cm H2O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required. PMID:22606029

  11. Sympathetic axonopathies and hyperinnervation in the small intestine smooth muscle of aged Fischer 344 rats

    PubMed Central

    Phillips, Robert J.; Hudson, Cherie N.; Powley, Terry L.

    2013-01-01

    It is well documented that the intrinsic enteric nervous system of the gastrointestinal (GI) tract sustains neuronal losses and reorganizes as it ages. In contrast, age-related remodeling of the extrinsic sympathetic projections to the wall of the gut is poorly characterized. The present experiment, therefore, surveyed the sympathetic projections to the aged small intestine for axonopathies. Furthermore, the experiment evaluated the specific prediction that catecholaminergic inputs undergo hyperplastic changes. Jejunal tissue was collected from 3-, 8-, 16-, and 24-month-old male Fischer 344 rats, prepared as whole mounts consisting of the muscularis, and processed immunohistochemically for tyrosine hydroxylase, the enzymatic marker for norepinephrine, and either the protein CD163 or the protein MHCII, both phenotypical markers for macrophages. Four distinctive sympathetic axonopathy profiles occurred in the small intestine of the aged rat: (1) swollen and dystrophic terminals, (2) tangled axons, (3) discrete hyperinnervated loci in the smooth muscle wall, including at the bases of Peyer's patches, and (4) ectopic hyperplastic or hyperinnervating axons in the serosa/subserosal layers. In many cases, the axonopathies occurred at localized and limited foci, involving only a few axon terminals, in a pattern consistent with incidences of focal ischemic, vascular, or traumatic insult. The present observations underscore the complexity of the processes of aging on the neural circuitry of the gut, with age-related GI functional impairments likely reflecting a constellation of adjustments that range from selective neuronal losses, through accumulation of cellular debris, to hyperplasias and hyperinnervation of sympathetic inputs. PMID:24104187

  12. The existence of a linear system consisting of sympathetic endings in rat skin.

    PubMed

    Liu, Li-Yuan; Zhang, Hui; Pan, Juan; Pen, An

    2005-09-01

    In a previous pilot study we suggested the novel notion that the catecholaminergic sympathetic nerve endings are non-homogeneously distributed in the rat skin. In the present study we have utilized several independent methods to determine the in vivo distribution of catecholamine-containing fibers in rat skin. Using whole body macro-autoradiography with an iodine125-labeled tyrosine, we localized the distribution of iodine-125-catecholamine in rat skin. The images on the film showed various pairs of symmetrical linear arrays running from the head through the back and to the hind limbs of the animal that we arbitrarily termed sympathetic substance lines (SSLs). The distribution of catecholamine in rat skin was also visualized by light microscopy autoradiography with tritiated tyrosine. The majority of silver grains in the sections were located among hair follicles along a band or zone. Furthermore, a modified sucrose-phosphate-glyoxilic acid (SPG) method was adapted to observe sympathetic fibers in the skin sections. Dense clusters of fluorescent nerve fibers in correspondence of arrector pili muscles (AP muscles) were located along lengthwise lines of the body, in a pattern coinciding with the linear arrays identified by macro-autoradiography. We concluded that concentrated clusters of noradrenergic nerve fibers innervate AP muscles and form a longitudinal linear system in the whole skin. These results are discussed in terms of physiological functions associated with hair follicles, sensory signal pathways and Meridians in Chinese traditional medicine. PMID:16133589

  13. Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats

    PubMed Central

    Lemes, Eduardo V.; Aiko, Simone; Orbem, Caroline B.; Formentin, Cleiton; Bassi, Mirian; Colombari, Eduardo; Zoccal, Daniel B.

    2015-01-01

    Aim Acute intermittent hypoxia (AIH) promotes persistent increases in ventilation and sympathetic activity, referred as long-term facilitation (LTF). Augmented inspiratory activity is suggested as a major component of respiratory LTF. In the present study, we hypothesized that AIH also elicits a sustained increase in expiratory motor activity. We also investigated whether the expiratory LTF contributes to the development of sympathetic LTF after AIH. Methods Rats were exposed to AIH (10 × 6–7 % O2 for 45 s, every 5 min) and the cardiorespiratory parameters were evaluated during 60 min using in vivo and in situ approaches. Results In unanesthetized conditions (n=9), AIH elicited a modest but sustained increase in baseline mean arterial pressure (MAP, 104±2 vs 111±3 mmHg, P<0.05) associated with enhanced sympathetic and respiratory-related variabilities. In the in situ preparations (n=9), AIH evoked LTF in phrenic (33±12%), thoracic sympathetic (75±25%) and abdominal nerve activities (69±14%). The sympathetic overactivity after AIH was phase-locked with the emergence of bursts in abdominal activity during the late-expiratory phase. In anesthetized vagus-intact animals, AIH increased baseline MAP (113±3 vs 122±2 mmHg, P<0.05) and abdominal muscle activity (535±94%), which were eliminated after pharmacological inhibition of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Conclusion These findings indicate that increased expiratory activity is also an important component of AIH-elicited respiratory LTF. Moreover, the development of sympathetic LTF after AIH is linked to the emergence of active expiratory pattern and depends on the integrity of the neurones of the RTN/pFRG. PMID:26910756

  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. Upregulation of orexin receptor in paraventricular nucleus promotes sympathetic outflow in obese Zucker rats

    PubMed Central

    Zhou, Jing-Jing; Yuan, Fang; Zhang, Yi; Li, De-Pei

    2015-01-01

    Sympathetic vasomotor tone is elevated in obesity-related hypertension. Orexin importantly regulates energy metabolism and autonomic function. We hypothesized that alteration of orexin receptor in the paraventricular nucleus (PVN) of the hypothalamus leads to elevated sympathetic vasomotor tone in obesity. We used in vivo measurement of sympathetic vasomotor tone and microinjection into brain nucleus, whole-cell patch clamp recording in brain slices, and immunocytochemical staining in obese Zucker rats (OZRs) and lean Zucker rats (LZRs). Microinjection of orexin 1 receptor (OX1R) antagonist SB334867 into the PVN reduced basal arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized OZRs but not in LZRs. Microinjection of orexin A into the PVN produced greater increases in ABP and RSNA in OZRs than in LZRs. Western blot analysis revealed that OX1R expression levels in the PVN were significantly increased in OZRs compared with LZRs. OX1R immunoreactivity was positive in retrogradely labeled PVN-spinal neurons. The basal firing rate of labeled PVN-spinal neurons was higher in OZRs than in LZRs. SB334867 decreased the basal firing activity of PVN-spinal neurons in OZRs but had no effect in LZRs. Orexin A induced a greater increase in the firing rate of PVN-spinal neurons in OZRs than in LZRs. In addition, orexin A induced larger currents in PVN-spinal neurons in OZRs than in LZRs. These data suggest that upregulation of OX1R in the PVN promotes hyperactivity of PVN presympathetic neurons and elevated sympathetic outflow in obesity. PMID:26277341

  16. 5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats.

    PubMed

    García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

    2015-09-01

    Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3±1.0, 43.7±2.7 and 66.7±4.0 for 2, 4 and 6Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT1/7 agonist) (0.00000125-0.1μg/kg each) or l-694,247 (5-HT1D agonist; 0.0125μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT2), 1-PBG (5-HT3), cisapride (5-HT4), AS-19 (5-HT7), CGS-12066B (5-HT1B) or 8-OH-DPAT (5-HT1A) (0.0125μg/kg each). The effect of l-694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT1D; 1mg/kg) or l-NAME (nitric oxide; 10mg/kg), but not by indomethacin (COX1/2; 2mg/kg) or glibenclamide (ATP-dependent K(+) channel; 20mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT1D receptors via nitric oxide release. PMID:26003124

  17. Continuous thoracic epidural anesthesia induces segmental sympathetic block in the awake rat.

    PubMed

    Freise, Hendrik; Anthonsen, Sören; Fischer, Lars G; Van Aken, Hugo K; Sielenkämper, Andreas W

    2005-01-01

    Thoracic epidural anesthesia (TEA) is used increasingly in critical care, especially for cardiac and intestinal sympathetic block. In this study we evaluated cardiorespiratory function and sympathetic activity in a new model of continuous TEA in awake rats. Thirteen rats received epidural saline control (CON) or bupivacaine 0.5% epidural infusion (EPI) at 15 microl/h for 2 h on day 1 and day 3. Mean arterial blood pressure, heart rate, respiration rate, arterial PCO2, and motor score were recorded at baseline and after 30, 60, 90, and 120 min. Skin temperature was measured at front paws, high-thoracic, mid-thoracic, and low-thoracic, hind paws, and the proximal and distal tail. Changes in sympathetic activity were assessed by skin temperature changes from baseline (DeltaT). In the EPI group, hemodynamics and respiration remained unchanged and only mild motor deficits occurred. DeltaT in thoracic segments was higher in the EPI than in the CON group (P <0.001 at all times at high-thoracic, mid-thoracic, and low-thoracic segments). Skin temperature decreased in the distal tail in the EPI group, e.g., after 90 min DeltaT=-0.86 +/- 0.25 degrees C (EPI) versus 0.4 +/- 0.12 degrees C (CON) (P <0.05 at 60, 90, and 120 min). DeltaT on day 3 was comparable to day 1. TEA induced stable segmental sympathetic block without cardiorespiratory and motor side effects in awake rats. This new technique may be applied in prolonged models of critical illness. PMID:15616087

  18. Modification of sympathetic neuronal function in the rat tail artery by dietary lipid treatment

    SciTech Connect

    Panek, R.L.; Dixon, W.R.; Rutledge, C.O.

    1985-06-01

    The effect of dietary lipid treatment on sympathetic neuronal function was examined in isolated perfused tail arteries of adult rats. The hypothesis that dietary manipulations alter the lipid environment of receptor proteins which may result in the perturbation of specific membrane-associated processes that regulate peripheral adrenergic neurotransmission in the vasculature was the basis for this investigation. In the present study, rats were fed semisynthetic diets enriched in either 16% coconut oil (saturated fat) or 16% sunflower oil (unsaturated fat). The field stimulation-evoked release of endogenous norepinephrine and total /sup 3/H was decreased significantly in rats receiving the coconut oil diet when compared to either sunflower oil- or standard lab chow-fed rats. Norepinephrine content in artery segments from coconut oil-treated rats was significantly higher compared to either sunflower oil- or standard lab chow-fed rats. Tail arteries from rats receiving the coconut oil diet displayed significantly lower perfusion pressure responses to nerve stimulation at all frequencies tested when compared to the sunflower oil- or standard lab chow-fed rats. Vasoconstrictor responses of perfused tail arteries exposed to exogenous norepinephrine resulted in an EC50 for norepinephrine that was not changed by the dietary treatment, but adult rats receiving the sunflower oil diet displayed a significantly greater maximum response to exogenous norepinephrine (10(-5) M) compared to arteries from either coconut oil- or standard lab chow-fed rats.

  19. Reactive Oxygen Species are involved in BMP-Induced Dendritic Growth in Cultured Rat Sympathetic Neurons

    PubMed Central

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J.

    2015-01-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons. PMID:26079955

  20. 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

  1. 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

  2. Increased peripherin in sympathetic axons innervating plantar metatarsal arteries in STZ-induced type I diabetic rats

    PubMed Central

    Johansen, Niloufer J.; Frugier, Tony; Hunne, Billie; Brock, James A.

    2014-01-01

    A common characteristic of axonopathy is the abnormal accumulation of cytoskeletal proteins. We recently reported that streptozotocin (STZ)-induced type 1 diabetes produced a change in the morphology of sympathetic nerve fibers supplying rat plantar metatarsal arteries (PMAs). Here we investigated whether these morphological changes are associated with axonal accumulation of the type III intermediate filament peripherin and the microtubule protein β-tubulin III, as both are implicated in axonal remodeling. PMAs from hyperglycemic STZ-treated rats receiving a low dose of insulin (STZ-LI) were compared with those from normoglycemic STZ-treated rats receiving a high dose of insulin (STZ-HI) and vehicle-treated controls. Western blotting revealed an increase in protein expression level for peripherin in PMAs from STZ-LI rats but no change in that for β-tubulin III. In addition, there was an increase in the number of peripherin immunoreactive nerve fibers in the perivascular nerve plexus of PMAs from STZ-LI rats. Co-labeling for peripherin and neuropeptide Y (a marker for sympathetic axons) revealed that peripherin immunoreactivity increased in sympathetic axons. None of these changes were detected in PMAs from STZ-HI rats, indicating that increased peripherin in sympathetic axons of STZ-LI rats is likely due to hyperglycemia and provides a marker of diabetes-induced nerve damage. PMID:24847201

  3. Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts

    PubMed Central

    Lee, Tsung-Ming; Chen, Wei-Ting; Yang, Chen-Chia; Lin, Shinn-Zong; Chang, Nen-Chung

    2015-01-01

    We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP-4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated formation of superoxide in the non-diabetic infarcted rats. PMID:25388908

  4. Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries

    PubMed Central

    Caracuel, Laura; Callejo, María; Balfagón, Gloria

    2015-01-01

    Background and Purpose We investigated whether pregnancy was associated with changed function in components of perivascular mesenteric innervation and the mechanism/s involved. Experimental Approach We used superior mesenteric arteries from female Sprague-Dawley rats divided into two groups: control rats (in oestrous phase) and pregnant rats (20 days of pregnancy). Modifications in the vasoconstrictor response to electrical field stimulation (EFS) were analysed in the presence/absence of phentolamine (alpha-adrenoceptor antagonist) or L-NAME (nitric oxide synthase-NOS- non-specific inhibitor). Vasomotor responses to noradrenaline (NA), and to NO donor DEA-NO were studied, NA and NO release measured and neuronal NOS (nNOS) expression/activation analysed. Key Results EFS induced a lower frequency-dependent contraction in pregnant than in control rats. Phentolamine decreased EFS-induced vasoconstriction in segments from both experimental groups, but to a greater extent in control rats. EFS-induced vasoconstriction was increased by L-NAME in arteries from both experimental groups. This increase was greater in segments from pregnant rats. Pregnancy decreased NA release while increasing NO release. nNOS expression was not modified but nNOS activation was increased by pregnancy. Pregnancy decreased NA-induced vasoconstriction response and did not modify DEA-NO-induced vasodilation response. Conclusions and Implications Neural control of mesenteric vasomotor tone was altered by pregnancy. Diminished sympathetic and enhanced nitrergic components both contributed to the decreased vasoconstriction response to EFS during pregnancy. All these changes indicate the selective participation of sympathetic and nitrergic innervations in vascular adaptations produced during pregnancy. PMID:25951331

  5. Omega-conotoxin GVIA is a potent inhibitor of sympathetic neurogenic responses in rat small mesenteric arteries.

    PubMed Central

    Pruneau, D.; Angus, J. A.

    1990-01-01

    1. We have investigated the effects of the N-type calcium channel blocker, omega-conotoxin GVIA, on contractile responses to nerve stimulation, noradrenaline and KCl in rat small mesenteric arteries. In separate experiments, single and summated excitatory junctional potentials (e.j.ps) evoked by nerve stimulation were recorded with an intracellular electrode in the absence and presence of omega-conotoxin. 2. Electrical field stimulation of intramural sympathetic nerves (30 V; 0.25 ms pulse width; 3 s train length; 4-24 Hz) caused frequency-dependent contractions. Cumulative concentration-response curves for the contractions induced by noradrenaline and KCl were constructed in the same preparations. Stimulation at 0.2 Hz and 10 Hz induced respectively single e.j.ps without contractions and summated e.j.ps associated with a contractile response. 3. omega-Conotoxin (0.1 to 3 nM) inhibited markedly and in a concentration-dependent manner both the contractions and e.j.ps to electrical field stimulation. The concentration-response curves to exogenous noradrenaline and KCl remained unaffected. 4. The time-course for the effects of omega-conotoxin (0.3 to 3 nM) indicated a slow onset of action with at least one hour to achieve an equilibrium. 5. The experiments indicate that omega-conotoxin acts prejunctionally to inhibit sympathetic neurotransmission in rat small arteries presumably by inhibition of noradrenaline release. We suggest that omega-conotoxin could be a useful tool to study the control of vascular tone through the autonomic nervous system. PMID:2372658

  6. 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

  7. Cardiac Dysregulation and Myocardial Injury in a 6-Hydroxydopamine-Induced Rat Model of Sympathetic Denervation

    PubMed Central

    Yang, Jin-long; Ma, Du-Fang; Lin, Hai-Qing; Su, Wen-ge; Wang, Zhen; Li, Xiao

    2015-01-01

    Background Cardiac sympathetic denervation is found in various cardiac pathologies; however, its relationship with myocardial injury has not been thoroughly investigated. Methods Twenty-four rats were assigned to the normal control group (NC), sympathectomy control group (SC), and a sympathectomy plus mecobalamin group (SM). Sympathectomy was induced by injection of 6-OHDA, after which, the destruction and distribution of sympathetic and vagal nerve in the left ventricle (LV) myocardial tissue were determined by immunofluorescence and ELISA. Heart rate variability (HRV), ECG and echocardiography, and assays for myocardial enzymes in serum before and after sympathectomy were examined. Morphologic changes in the LV by HE staining and transmission electron microscope were used to estimate levels of myocardial injury and concentrations of inflammatory cytokines were used to reflect the inflammatory reaction. Results Injection of 6-OHDA decreased NE (933.1 ± 179 ng/L for SC vs. 3418.1± 443.6 ng/L for NC, P < 0.01) and increased NGF (479.4± 56.5 ng/mL for SC vs. 315.85 ± 28.6 ng/mL for NC, P < 0.01) concentrations. TH expression was reduced, while ChAT expression showed no change. Sympathectomy caused decreased HRV and abnormal ECG and echocardiography results, and histopathologic examinations showed myocardial injury and increased collagen deposition as well as inflammatory cell infiltration in the cardiac tissue of rats in the SC and SM groups. However, all pathologic changes in the SM group were less severe compared to those in the SC group. Conclusions Chemical sympathectomy with administration of 6-OHDA caused dysregulation of the cardiac autonomic nervous system and myocardial injuries. Mecobalamin alleviated inflammatory and myocardial damage by protecting myocardial sympathetic nerves. PMID:26230083

  8. Sympathetic activation by chemical stimulation of white adipose tissues in rats.

    PubMed

    Shi, Zhen; Chen, Wei-Wei; Xiong, Xiao-Qing; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-03-01

    Injection of leptin into white adipose tissue (WAT) increases sympathetic outflow. The present study was designed to determine the effects of capsaicin and other chemicals in WAT on the sympathetic outflow and blood pressure and the roles of WAT afferents and hypothalamic paraventricular nucleus (PVN) in the adipose afferent reflex (AAR). The AAR was induced by injection of capsaicin, bradykinin, adenosine, adenosine triphosphate (ATP), or leptin into inguinal WAT (iWAT) or retroperitoneal WAT (rWAT) in anesthetized rats. The iWAT injection of capsaicin increased the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) but not the heart rate. Bradykinin, adenosine, or leptin but not ATP in the iWAT caused similar effects to capsaicin on the RSNA and MAP. Intravenous, intramuscular, or intradermal injection of capsaicin had no significant effects on the RSNA and MAP. The effects of capsaicin in rWAT were similar to that in iWAT on the RSNA and MAP. Furthermore, injection of capsaicin into the iWAT increased the WAT afferent nerve activities, WAT efferent nerve activity, and brown adipose tissue efferent nerve activity. The iWAT denervation or chemical lesion of the PVN neurons with kainic acid abolished the AAR induced by the iWAT injection of capsaicin. These results indicate that the stimulation of iWAT afferents with capsaicin, bradykinin, adenosine, or leptin reflexly increases the RSNA and blood pressure. The iWAT afferents and the PVN are involved in the AAR induced by capsaicin in the iWAT. PMID:22223453

  9. Nociception attenuates parasympathetic but not sympathetic baroreflex via NK1 receptors in the rat nucleus tractus solitarii

    PubMed Central

    Pickering, Anthony E; Boscan, Pedro; Paton, Julian F R

    2003-01-01

    Somatic noxious stimulation can evoke profound cardiovascular responses by altering activity in the autonomic nervous system. This noxious stimulation attenuates the cardiac vagal baroreflex, a key cardiovascular homeostatic reflex. This attenuation is mediated via NK1 receptors expressed on GABAergic interneurones within the nucleus of the solitary tract (NTS). We have investigated the effect of noxious stimulation and exogenous substance P (SP) on the sympathetic component of the baroreflex. We recorded from the sympathetic chain in a decerebrate, artificially perfused rat preparation. Noxious hindlimb pinch was without effect on the sympathetic baroreflex although the cardiac vagal baroreflex gain was decreased (56%, P < 0.01). Bilateral NTS microinjection of SP (500 fmol) produced a similar selective attenuation of the cardiac vagal baroreflex gain (62%, P < 0.005) without effect on the sympathetic baroreflex. Recordings from the cardiac sympathetic and vagal nerves confirmed the selectivity of the SP inhibition. Control experiments using a GABAA receptor agonist, isoguvacine, indicated that both components of the baroreflex (parasympathetic and sympathetic) could be blocked from the NTS injection site. The NTS microinjection of a NK1 antagonist (CP-99,994) in vivo attenuated the tachycardic response to hindlimb pinch. Our data suggest that noxious pinch releases SP within the NTS to selectively attenuate the cardiac vagal, but not the sympathetic, component of the baroreflex. This selective withdrawal of the cardiac vagal baroreflex seems to underlie the pinch-evoked tachycardia seen in vivo. Further, these findings confirm that baroreflex sympathetic and parasympathetic pathways diverge, and can be independently controlled, within the NTS. PMID:12813142

  10. Nociception attenuates parasympathetic but not sympathetic baroreflex via NK1 receptors in the rat nucleus tractus solitarii.

    PubMed

    Pickering, Anthony E; Boscan, Pedro; Paton, Julian F R

    2003-09-01

    Somatic noxious stimulation can evoke profound cardiovascular responses by altering activity in the autonomic nervous system. This noxious stimulation attenuates the cardiac vagal baroreflex, a key cardiovascular homeostatic reflex. This attenuation is mediated via NK1 receptors expressed on GABAergic interneurones within the nucleus of the solitary tract (NTS). We have investigated the effect of noxious stimulation and exogenous substance P (SP) on the sympathetic component of the baroreflex. We recorded from the sympathetic chain in a decerebrate, artificially perfused rat preparation. Noxious hindlimb pinch was without effect on the sympathetic baroreflex although the cardiac vagal baroreflex gain was decreased (56 %, P < 0.01). Bilateral NTS microinjection of SP (500 fmol) produced a similar selective attenuation of the cardiac vagal baroreflex gain (62 %, P < 0.005) without effect on the sympathetic baroreflex. Recordings from the cardiac sympathetic and vagal nerves confirmed the selectivity of the SP inhibition. Control experiments using a GABAA receptor agonist, isoguvacine, indicated that both components of the baroreflex (parasympathetic and sympathetic) could be blocked from the NTS injection site. The NTS microinjection of a NK1 antagonist (CP-99,994) in vivo attenuated the tachycardic response to hindlimb pinch. Our data suggest that noxious pinch releases SP within the NTS to selectively attenuate the cardiac vagal, but not the sympathetic, component of the baroreflex. This selective withdrawal of the cardiac vagal baroreflex seems to underlie the pinch-evoked tachycardia seen in vivo. Further, these findings confirm that baroreflex sympathetic and parasympathetic pathways diverge, and can be independently controlled, within the NTS. PMID:12813142

  11. Role of neuronal nitric oxide in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats.

    PubMed

    Jendzjowsky, Nicholas G; DeLorey, Darren S

    2013-07-01

    Isoform-specific nitric oxide (NO) synthase (NOS) contributions to NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle are incompletely understood. The purpose of the present study was to investigate the role of neuronal NOS (nNOS) in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats. We hypothesized that acute pharmacological inhibition of nNOS would augment sympathetic vasoconstriction in resting and contracting skeletal muscle, demonstrating that nNOS is primarily responsible for NO-mediated inhibition of sympathetic vasoconstriction. Sprague-Dawley rats (n = 13) were anesthetized and instrumented with an indwelling brachial artery catheter, femoral artery flow probe, and lumbar sympathetic chain stimulating electrodes. Triceps surae muscles were stimulated to contract rhythmically at 60% of maximal contractile force. In series 1 (n = 9), the percent change in femoral vascular conductance (%FVC) in response to sympathetic stimulations delivered at 2 and 5 Hz was determined at rest and during muscle contraction before and after selective nNOS blockade with S-methyl-l-thiocitrulline (SMTC, 0.6 mg/kg iv) and subsequent nonselective NOS blockade with N(ω)-nitro-l-arginine methyl ester (l-NAME, 5 mg/kg iv). In series 2 (n = 4), l-NAME was injected first, and then SMTC was injected to determine if the effect of l-NAME on constrictor responses was influenced by selective nNOS inhibition. Sympathetic stimulation decreased FVC at rest (-25 ± 7 and -44 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (-7 ± 3 and -19 ± 5%FVC at 2 and 5 Hz, respectively). The decrease in FVC in response to sympathetic stimulation was greater in the presence of SMTC at rest (-32 ± 6 and -49 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (-21 ± 4 and -28 ± 4%FVC at 2 and 5 Hz, respectively). l-NAME further increased (P < 0.05) the sympathetic vasoconstrictor

  12. Circadian changes in autonomic function in conscious rats with heart failure: effects of amiodarone on sympathetic surge.

    PubMed

    Ohori, Takashi; Hirai, Tadakazu; Joho, Shuji; Kameyama, Tomoki; Nozawa, Takashi; Asanoi, Hidetsugu; Inoue, Hiroshi

    2011-01-20

    Cardiovascular events are characterized by circadian periodicity with a peak prevalence during the awakening period, which suggests a morning surge in sympathetic activity. We developed an experimental system to determine circadian changes in heart rate (HR), blood pressure (BP), locomotor activity (Loc), respiratory rate and autonomic function in conscious, unrestrained rats. The effects of amiodarone on circadian variation of these variables were determined in rats with myocardial infarction and subsequent congestive heart failure (CHF). We continuously recorded BP, HR and Loc for 24h in rats with CHF (n=16) or after a sham operation (Sham; n=7). To determine circadian changes in sympathovagal balance, digitized BP and HR data throughout 24h were analyzed based on maximum entropy. The study was repeated after 3 weeks of oral amiodarone (50mg/kg/day) or saline administration. Baseline HR, mean BP, and Loc were higher in the dark period than in the light period (all p<0.05) in both CHF and Sham rats, which is consistent with the circadian periodicity of nocturnal animals. Low-frequency components of diastolic BP variability (LFdp), an index of sympathetic tone, were significantly higher during the awakening period (16:00-20:00) than during the sleeping period (08:00-14:00), a finding analogous to the sympathetic morning surge in men. Amiodarone suppressed this transient increase in LFdp power during the awakening period. Our experimental system could detect sympathetic surge in conscious rats. Amiodarone suppressed the sympathetic surge, which could explain, at least in part, beneficial effects of amiodarone in patients with CHF. PMID:20674512

  13. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

    PubMed Central

    2011-01-01

    Background Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE) release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ) rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function. Methods Cardiac sympathetic nervous integrity was investigated in vivo via biodistribution of the positron emission tomography radiotracer and NE analogue [11C]meta-hydroxyephedrine ([11C]HED). Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET) expression were evaluated as correlative measurements. Results The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [11C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle. Conclusions Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system signaling in the absence of

  14. Peripheral Hot Spots for Local Ca2+ Release after Single Action Potentials in Sympathetic Ganglion Neurons

    PubMed Central

    Cseresnyés, Zoltán; Schneider, Martin F.

    2004-01-01

    Ca2+ release from the endoplasmic reticulum (ER) contributes to Ca2+ transients in frog sympathetic ganglion neurons. Here we use video-rate confocal fluo-4 fluorescence imaging to show that single action potentials reproducibly trigger rapidly rising Ca2+ transients at 1–3 local hot spots within the peripheral ER-rich layer in intact neurons in fresh ganglia and in the majority (74%) of cultured neurons. Hot spots were located near the nucleus or the axon hillock region. Other regions exhibited either slower and smaller signals or no response. Ca2+ signals spread into the cell at constant velocity across the ER in nonnuclear regions, indicating active propagation, but spread with a (time)1/2 dependence within the nucleus, consistent with diffusion. 26% of cultured cells exhibited uniform Ca2+ signals around the periphery, but hot spots were produced by loading the cytosol with EGTA or by bathing such cells in low-Ca2+ Ringer's solution. Peripheral hot spots for Ca2+ release within the perinuclear and axon hillock regions provide a mechanism for preferential initiation of nuclear and axonal Ca2+ signals by single action potentials in sympathetic ganglion neurons. PMID:14695260

  15. 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

  16. 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. PMID:26988151

  17. 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

  18. 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

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

    PubMed Central

    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

  20. Vasovagal oscillations and vasovagal responses produced by the vestibulo-sympathetic reflex in the rat.

    PubMed

    Yakushin, Sergei B; Martinelli, Giorgio P; Raphan, Theodore; Xiang, Yongqing; Holstein, Gay R; Cohen, Bernard

    2014-01-01

    Sinusoidal galvanic vestibular stimulation (sGVS) induces oscillations in blood pressure (BP) and heart rate (HR), i.e., vasovagal oscillations, as well as transient decreases in BP and HR, i.e., vasovagal responses, in isoflurane-anesthetized rats. We determined the characteristics of the vasovagal oscillations, assessed their role in the generation of vasovagal responses, and determined whether they could be induced by monaural as well as by binaural sGVS and by oscillation in pitch. Wavelet analyses were used to determine the power distributions of the waveforms. Monaural and binaural sGVS and pitch generated vasovagal oscillations at the frequency and at twice the frequency of stimulation. Vasovagal oscillations and vasovagal responses were maximally induced at low stimulus frequencies (0.025-0.05 Hz). The oscillations were attenuated and the responses were rarely induced at higher stimulus frequencies. Vasovagal oscillations could occur without induction of vasovagal responses, but vasovagal responses were always associated with a vasovagal oscillation. We posit that the vasovagal oscillations originate in a low frequency band that, when appropriately activated by strong sympathetic stimulation, can generate vasovagal oscillations as a precursor for vasovagal responses and syncope. We further suggest that the activity responsible for the vasovagal oscillations arises in low frequency, otolith neurons with orientation vectors close to the vertical axis of the head. These neurons are likely to provide critical input to the vestibulo-sympathetic reflex to increase BP and HR upon changes in head position relative to gravity, and to contribute to the production of vasovagal oscillations and vasovagal responses and syncope when the baroreflex is inactivated. PMID:24772102

  1. Reflex control of rat tail sympathetic nerve activity by abdominal temperature

    PubMed Central

    Shafton, Anthony D; Kitchener, Peter; McKinley, Michael J; McAllen, Robin M

    2014-01-01

    The thermoregulatory reflex effects of warming and cooling in the abdomen were investigated in 4 urethane-anesthetized Sprague-Dawley rats. Animals were shaved and surrounded by a water-perfused silastic jacket. Skin temperature under the jacket was recorded by thermocouples at 3 sites and brain temperature was monitored by a thermocouple inserted lateral to the hypothalamus. A heat exchanger made from an array of silicon tubes in parallel loops was placed through a ventral incision into the abdomen; it rested against the intestinal serosa and the temperature of this interface was monitored by a thermocouple. Few- or multi-unit postganglionic activity was recorded from sympathetic nerves supplying tail vessels (tail SNA). Intra-abdominal temperature was briefly lowered or raised between 35–41 °C by perfusing the heat exchanger with cold or warm water. Warming the abdomen inhibited tail SNA while cooling it excited tail SNA in all 4 animals. We also confirmed that cooling the trunk skin activated tail SNA. Multivariate analysis of tail SNA with respect to abdominal, brain and trunk skin temperatures revealed that all had highly significant independent inhibitory actions on tail SNA, but in these experiments abdominal temperature had the weakest and brain temperature the strongest effect. We conclude that abdominal temperature has a significant thermoregulatory action in the rat, but its influence on cutaneous vasomotor control appears to be weaker than that of skin or brain temperatures.

  2. Altered firing pattern of single-unit muscle sympathetic nerve activity during handgrip exercise in chronic heart failure

    PubMed Central

    Murai, Hisayoshi; Takamura, Masayuki; Maruyama, Michirou; Nakano, Manabu; Ikeda, Tatsunori; Kobayashi, Daisuke; Otowa, Kan-ichi; Ootsuji, Hiroshi; Okajima, Masaki; Furusho, Hiroshi; Takata, Shigeo; Kaneko, Shuichi

    2009-01-01

    Sympathetic activation in chronic heart failure (CHF) is greatly augmented at rest but the response to exercise remains controversial. We previously demonstrated that single-unit muscle sympathetic nerve activity (MSNA) provides a more detailed description of the sympathetic response to physiological stress than multi-unit nerve recordings. The purpose of this study was to determine whether the reflex response and discharge properties of single-unit MSNA are altered during handgrip exercise (HG, 30% of maximum voluntary contraction for 3 min) in CHF patients (New York Heart Association functional class II or III, n= 16) compared with age-matched healthy control subjects (n= 13). At rest, both single-unit and multi-unit indices of sympathetic outflow were augmented in CHF compared with controls (P < 0.05). However, the percentage of cardiac intervals that contained one, two, three or four single-unit spikes were not different between the groups. Compared to the control group, HG elicited a larger increase in multi-unit total MSNA (Δ1002 ± 50 compared with Δ636 ± 76 units min−1, P < 0.05) and single-unit MSNA spike incidence (Δ27 ± 5 compared with Δ8 ± 2 spikes (100 heart beats)−1), P < 0.01) in the CHF patients. More importantly, the percentage of cardiac intervals that contained two or three single-unit spikes was increased (P < 0.05) during exercise in the CHF group only (Δ8 ± 2% and Δ5 ± 1% for two and three spikes, respectively). These results suggest that the larger multi-unit total MSNA response observed during HG in CHF is brought about in part by an increase in the probability of multiple firing of single-unit sympathetic neurones. PMID:19403612

  3. Peripheral nerve injury leads to the establishment of a novel pattern of sympathetic fibre innervation in the rat skin.

    PubMed

    Ruocco, I; Cuello, A C; Ribeiro-Da-Silva, A

    2000-06-26

    Peripheral nerve injury has been shown to result in sympathetic fibre sprouting around dorsal root ganglia (DRG) neurons. It has been suggested that this anomalous sympathetic fibre innervation of the DRG plays a role in neuropathic pain. Other studies have suggested an interaction between sympathetic and sensory fibres more peripherally. To date, no anatomical study of these possible interactions in the terminal fields of sensory and sympathetic fibres has been performed; therefore, the authors set out to study them in the rat lower lip after bilateral lesions of a sensory nerve, the mental nerve (MN). Immunocytochemistry for both substance P (SP) and dopamine-beta-hydroxylase (DbetaH) was performed. Within the first week post-MN lesions, the SP-immunoreactive (IR) fibres had degenerated almost completely, whereas DbetaH-IR fibres were found in the upper dermis, an area from which they normally are absent. These DbetaH-IR fibres were present in the upper dermis at all postsurgery times studied (1, 2, 3, 4, 6, and 8 weeks). It is noteworthy that, although, by week 6 post-MN lesions, SP-IR fibre reinnervation of the lower lip was occurring, the DbetaH-IR fibres still were present in the upper dermis. Quantification revealed that the migration and branching of the DbetaH-IR fibres into the upper dermis occurred gradually and was most significant at 4 weeks post-MN lesions, as demonstrated by the fact that the DbetaH-IR fibres were found 169.6 +/- 91.4 microm away from the surface of the skin compared with 407.1 +/- 78.4 microm away in sham-operated animals. These findings suggest that the ectopic innervation of the upper dermis by sympathetic fibres may be important in the genesis of neuropathic pain through the interactions of sympathetic and SP-containing sensory fibres. PMID:10842232

  4. 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

  5. Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats

    PubMed Central

    2011-01-01

    Background This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats. Methods Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME). Results In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists. Conclusions Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats. PMID:21047287

  6. Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats

    PubMed Central

    Briant, Linford J. B.; Stalbovskiy, Alexey O.; Nolan, Matthew F.; Champneys, Alan R.

    2014-01-01

    Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15–30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. PMID:25122704

  7. Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

    PubMed

    Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

    2014-12-01

    Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. PMID:25122704

  8. Hierarchical recruitment of the sympathetic and parasympathetic limbs of the baroreflex in normotensive and spontaneously hypertensive rats.

    PubMed

    Simms, Annabel E; Paton, Julian F R; Pickering, Anthony E

    2007-03-01

    The arterial baroreflex acts to buffer acute changes in blood pressure by reciprocal modulation of sympathetic and parasympathetic activity that controls the heart and vasculature. We have examined the baroreflex pressure-function curves for changes in heart rate and non-cardiac sympathetic nerve activity (SNA, thoracic chain T8-12) in artificially perfused in situ rat preparations. We found that the non-cardiac SNA baroreflex is active over a lower range of pressures than the cardiac baroreflex (threshold 66 +/- 1 mmHg versus 82 +/- 5 mmHg and mid-point 77 +/- 3 versus 87 +/- 4 mmHg, respectively, P < 0.05, n = 6). This can manifest as a complete dissociation of the baroreflex limbs at low pressures. This difference between the cardiac and non-cardiac SNA baroreflex is also seen in end-organ sympathetic outflows (adrenal and renal nerves). Recordings of the cardiac vagal (parasympathetic) and the inferior cardiac (sympathetic) nerves identify the cardiac parasympathetic baroreflex component as being active over a higher range of pressures. This difference in the operating range of the baroreflex-function curves is exaggerated in the spontaneously hypertensive rat where the cardiac component has selectively reset by 20-25 mmHg to a higher pressure range (threshold of 104 +/- 4 mmHg and mid-point 113 +/- 4, n = 6). The difference in the pressure-function curves for the cardiac versus the vascular baroreflex indicates that there is a hierarchical recruitment of the output limbs of the baroreflex with a sympathetic predominance at lower arterial pressures. PMID:17170043

  9. TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion

    PubMed Central

    Xing, Jihong; Lu, Jian; Li, Jianhua

    2015-01-01

    Autonomic responses to activation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1) has been reported to contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP) responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves' TRPA1 plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24–72 h of femoral artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV); and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia. PMID:26441669

  10. Pharmacological evidence that dopamine inhibits the cardioaccelerator sympathetic outflow via D2-like receptors in pithed rats.

    PubMed

    Alcántara-Vázquez, Oscar; Villamil-Hernández, Ma Trinidad; Sánchez-López, Araceli; Centurión, David

    2013-01-01

    It has been suggested that N,N-di-n-propyl-dopamine (dopamine analogue) decreased heart rate in rats through stimulation of dopamine receptors. Nevertheless, the role of prejunctional dopamine D1/2-like receptors or even α2-adrenoceptors to mediate cardiac sympatho-inhibition induced by dopamine remains unclear. Hence, this study identified the pharmacological profile of the cardiac sympatho-inhibition to dopamine in pithed rats. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. I.v. continuous infusions of dopamine (endogenous ligand) or quinpirole (D2-like agonist) dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. In contrast, SKF-38393 (100 μg/kg∙min, D1-like agonist) failed to modify both of these responses. The sympatho-inhibition to dopamine (1.8 μg/kg∙min) or quinpirole (100 μg/kg∙min): i) remained unaltered after saline or the antagonists SCH-23390 (D1-like, 300 μg/kg) and rauwolscine (α2-adrenoceptors, 300 μg/kg); and ii) was significantly antagonized by raclopride (D2-like, 300 μg/kg). These antagonists, at the above doses, failed to modify the sympathetically-induced tachycardic responses. The above results suggest that the inhibition of the cardiac sympathetic outflow to dopamine and quinpirole is primarily mediated by prejunctional D2-like receptors but not D1-like receptors or α2-adrenoceptors. PMID:24225403

  11. Potassium activation of [3H]-choline accumulation by isolated sympathetic ganglia of the rat.

    PubMed Central

    Higgins, A. J.; Neal, M. J.

    1982-01-01

    1 The effect of K-depolarization on the uptake of low and high concentrations of [3H]-choline by isolated superior sympathetic ganglia of the rat has been studied. 2 In unstimulated ganglia, the uptake of [3H]-choline (0.1 microM) ('high affinity uptake') was unaffected by denervation or by hemicholinium-3 (HC-3), suggesting uptake by structures other than cholinergic nerve terminals. 3 K-depolarization of the ganglia increased [3H]-choline accumulation by the high affinity uptake process but in contrast the 'low affinity' accumulation of [3H]-choline (100 microM) was decreased. 4 The K-activated, 'high affinity' component of choline uptake was highly sodium-dependent, inhibited by HC-3, and was abolished by denervation. 5 In incubation conditions designed to prevent transmitter release (Ca-free medium and high-Mg medium), the K-activated uptake of [3H]-choline was abolished. 6 It is concluded that in unstimulated ganglia, there is little choline uptake by nerve terminals. However, when the terminals are depolarized, choline uptake is increased by the activation of a sodium-dependent, HC-3-sensitive transport process. The activation of this uptake process is apparently associated with the release of acetylcholine from the terminals, or by changes in ionic fluxes, and not by the depolarization per se. PMID:7150866

  12. Involvement of sympathetic function in the sleep-related change of gastric myoelectrical activity in rats.

    PubMed

    Huang, Yu-Min; Yang, Cheryl C H; Lai, Ching Jung; Kuo, Terry B J

    2010-03-01

    The gastric myoelectrical activity (GMA) fluctuates across sleep-wake states as a result of modulation by the brain-gut axis. The role of the autonomic nervous system in this phenomenon, however, was not elucidated fully. Through simultaneous recording and subsequent continuous power spectral analysis of electroencephalogram, electromyogram, electrocardiogram and electrogastromyogram (EGMG) in 16 freely moving Wistar rats, the sleep-wake states of the animals were defined and indices of cardiac autonomic regulation and GMA were calculated. We found that both cardiac autonomic regulation and GMA fluctuated through sleep-wake cycles. Correlation analysis further revealed significant correlations between EGMG power and each of the R-R interval, high-frequency power, low-frequency power, very-low-frequency power, low-frequency power to high-frequency power ratio and normalized low-frequency power of heart rate variability with respect to their trend of change across different sleep-wake states. These results suggest that the sleep-wake-related change of GMA was related to sympathovagal balance. The sympathetic nerve may play a more important role in the central modulation of GMA than perceived previously. PMID:19845848

  13. 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

  14. 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

  15. Neurochemical evidence for the presence of sympathetic nerve terminals in the rat mammary gland: Changes during the lactogenic cycle.

    PubMed

    Donoso, E A; Sapag-Hagar, M; Lara, H E

    1992-02-01

    Experiments were undertaken to obtain neurochemical evidence of the presence of sympathetic nerve terminals in the rat mammary gland and the changes occurring in them during the lactogenic cycle. The norepinephrine (NE) content of the gland changed during the lactogenic cycle. Higher levels of NE were found during virginity and involution, whereas a lower level was found at 14 days of lactation. Surgical and chemical (with 6-hydroxydopamine) denervation reduced the norepinephrine content of the gland by 61 and 90%, respectively. Uptake of [(3)H]norepinephrine by the mammary gland was saturable and specifically blocked by cocaine. No changes in the maximal capacity of incorporation during the lactogenic cycle were found, but the affinity of NE for the transmembrane carrier was low during lactation, as was the NE content, suggesting a decrease in the sympathetic nerve activity during this stage of the lactogenic cycle. In support of this, we found a decrease in total NE released after stimulation with 80 mM KCI. The neurochemical evidence obtained during this research strongly suggests that rat mammary gland is innervated by sympathetic nerves and that their activity changes during the lactogenic cycle. PMID:19912841

  16. Changes in baroreflex control of renal sympathetic nerve activity in high-fat-fed rats as a predictor of hypertension.

    PubMed

    Fardin, Núbia M; Oyama, Lila M; Campos, Ruy R

    2012-08-01

    There is evidence that obesity is associated with increased sympathetic activity and hypertension. However, the mechanisms responsible for these changes are not fully understood. Therefore, the aim of the present study was to evaluate the cardiovascular function and the baroreceptor reflex control of renal sympathetic nerve activity (rSNA) in rats exposed to a high-fat diet over different periods (10 and 20 weeks) compared to control rats. Serum leptin levels were assessed for all time points. Male Wistar rats weighing 150-180 g were used. Four groups of rats were studied: control 10 weeks (Ct10), obese 10 weeks (Ob10), control 20 weeks (Ct20), and obese 20 weeks (Ob20). Blood pressure (BP) and rSNA were recorded in urethane-anesthetized rats (1.4 g/kg, intravenous).The sensitivity of rSNA responses to baroreceptor reflex was assessed by changes in BP induced by increasing doses of phenylephrine or sodium nitroprusside. Significant and progressive increases in serum leptin levels were found in the obese rats, but not in the control rats. No changes in basal BP or rSNA were found in the Ob10 and Ob20 groups; however, a significant impairment in the baroreceptor sensitivity was observed in the Ob20 group for phenylephrine (slope Ob20: -0.78 ± 0.12 vs. Ct20: -1.00 ± 0.08 potential per second (pps)/mm Hg, P < 0.05) and sodium nitroprusside (slope Ob20: -0.82 ± 0.09 vs. 1.13 ± 0.13 pps/mm Hg, P < 0.05). The results suggest that the baroreceptor dysfunction that controls the rSNA is an initial change in the obesity induced in high-fat-fed rats, which might be a predictor of sympathoexcitation and hypertension associated to obesity. PMID:22257982

  17. 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

  18. Individual sympathetic postganglionic neurons coinnervate myenteric ganglia and smooth muscle layers in the gastrointestinal tract of the rat.

    PubMed

    Walter, Gary C; Phillips, Robert J; McAdams, Jennifer L; Powley, Terry L

    2016-09-01

    A full description of the terminal architecture of sympathetic axons innervating the gastrointestinal (GI) tract has not been available. To label sympathetic fibers projecting to the gut muscle wall, dextran biotin was injected into the celiac and superior mesenteric ganglia (CSMG) of rats. Nine days postinjection, animals were euthanized and stomachs and small intestines were processed as whole mounts (submucosa and mucosa removed) to examine CSMG efferent terminals. Myenteric neurons were counterstained with Cuprolinic Blue; catecholaminergic axons were stained immunohistochemically for tyrosine hydroxylase. Essentially all dextran-labeled axons (135 of 136 sampled) were tyrosine hydroxylase-positive. Complete postganglionic arbors (n = 154) in the muscle wall were digitized and analyzed morphometrically. Individual sympathetic axons formed complex arbors of varicose neurites within myenteric ganglia/primary plexus and, concomitantly, long rectilinear arrays of neurites within circular muscle/secondary plexus or longitudinal muscle/tertiary plexus. Very few CSMG neurons projected exclusively (i.e., ∼100% of an arbor's varicose branches) to myenteric plexus (∼2%) or smooth muscle (∼14%). With less stringent inclusion criteria (i.e., ≥85% of an axon's varicose branches), larger minorities of neurons projected predominantly to either myenteric plexus (∼13%) or smooth muscle (∼27%). The majority (i.e., ∼60%) of all individual CSMG postganglionics formed mixed, heterotypic arbors that coinnervated extensively (>15% of their varicose branches per target) both myenteric ganglia and smooth muscle. The fact that ∼87% of all sympathetics projected either extensively or even predominantly to smooth muscle, while simultaneously contacting myenteric plexus, is consistent with the view that these neurons control GI muscle directly, if not exclusively. J. Comp. Neurol. 524:2577-2603, 2016. © 2016 Wiley Periodicals, Inc. PMID:26850701

  19. Contribution of adenosine to the depression of sympathetically evoked vasoconstriction induced by systemic hypoxia in the rat

    PubMed Central

    Coney, Andrew M; Marshall, Janice M

    2003-01-01

    Previous studies have shown that systemic hypoxia evokes vasodilatation in skeletal muscle that is mediated mainly by adenosine acting on A1 receptors, and that the vasoconstrictor effects of sympathetic nerve activity are depressed during hypoxia. The aim of the present study was to investigate the role of adenosine in this depression. In anaesthetised rats, increases in femoral vascular resistance (FVR) evoked by stimulation of the lumbar sympathetic chain with bursts of impulses at 40 or 20 Hz were greater than those evoked by continuous stimulation at 2 Hz with the same number of impulses (120) over 1 min. All of these responses were substantially reduced by infusion of adenosine or by graded systemic hypoxia (breathing 12, 10 or 8 % O2), increases in FVR evoked by continuous stimulation at 2 Hz being most vulnerable. Blockade of A1 receptors ameliorated the depression caused by adenosine infusion of the increase in FVR evoked by 2 Hz only and did not ameliorate the depression caused by 8 % O2 of increases in FVR evoked by any pattern of sympathetic stimulation. A2A receptor blockade accentuated hypoxia-induced depression of the increase in FVR evoked by burst stimulation at 40 Hz, but had no other effect. Neither A1 nor A2A receptor blockade affected the depression caused by hypoxia (8 % O2) of the FVR increase evoked by noradrenaline infusion. These results indicate that endogenously released adenosine is not responsible for the depression of sympathetically evoked muscle vasoconstriction caused by systemic hypoxia; adenosine may exert a presynaptic facilitatory influence on the vasoconstrictor responses evoked by bursts at high frequency. PMID:12702736

  20. 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

  1. Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat

    PubMed Central

    Schreihofer, Ann M; Stornetta, Ruth L; Guyenet, Patrice G

    2000-01-01

    In this study we examined whether the rostral ventrolateral medulla (RVLM) maintains resting sympathetic vasomotor tone and activates sympathetic nerve activity (SNA) after the depletion of bulbospinal C1 adrenergic neurones. Bulbospinal C1 cells were destroyed (≈84% loss) by bilateral microinjections (spinal segments T2-T3) of an anti-dopamine-β-hydroxylase antibody conjugated to the ribosomal toxin saporin (anti-DβH-SAP). Extracellular recording and juxtacellular labelling of bulbospinal barosensitive neurones in the RVLM revealed that treatment with anti-DβH-SAP spared the lightly myelinated neurones with no tyrosine hydroxylase immunoreactivity. In rats treated with anti-DβH-SAP, inhibition of RVLM neurones by bilateral microinjection of muscimol eliminated splanchnic SNA and produced the same degree of hypotension as in control rats. Following treatment with anti-DβH-SAP the sympathoexcitatory (splanchnic nerve) and pressor responses to electrical stimulation of the RVLM were reduced. Treatment with anti-DβH-SAP also eliminated the majority of A5 noradrenergic neurones. However, rats with selective lesion of A5 cells by microinjection of 6-hydroxydopamine into the pons showed no deficits to stimulation of the RVLM. In summary, the loss of 84% of bulbospinal adrenergic neurones does not alter the ability of RVLM to maintain SNA and arterial pressure at rest in anaesthetized rats, but this loss reduces the sympathoexcitatory and pressor responses evoked by RVLM stimulation. The data suggest sympathoexcitatory roles for both the C1 cells and non-C1 cells of the RVLM and further suggest the C1 cells are critical for the full expression of sympathoexcitatory responses generated by the RVLM. PMID:11080264

  2. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring.

    PubMed

    García, Ana Paula; Palou, Mariona; Sánchez, Juana; Priego, Teresa; Palou, Andreu; Picó, Catalina

    2011-01-01

    Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT) sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively) were analyzed in male and female offspring of control and 20% caloric-restricted (from 1-12 d of pregnancy) (CR) dams. Body weight (BW), the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry) of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH(+) and NPY(+), suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH(+) and NPY(+). Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture. PMID:21364997

  3. Moderate Caloric Restriction during Gestation in Rats Alters Adipose Tissue Sympathetic Innervation and Later Adiposity in Offspring

    PubMed Central

    García, Ana Paula; Palou, Mariona; Sánchez, Juana; Priego, Teresa; Palou, Andreu; Picó, Catalina

    2011-01-01

    Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT) sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively) were analyzed in male and female offspring of control and 20% caloric-restricted (from 1–12 d of pregnancy) (CR) dams. Body weight (BW), the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry) of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH+ and NPY+, suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH+ and NPY+. Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture. PMID:21364997

  4. Virtual leak channels modulate firing dynamics and synaptic integration in rat sympathetic neurons: implications for ganglionic transmission in vivo

    PubMed Central

    Springer, Mitchell G; Kullmann, Paul H M; Horn, John P

    2015-01-01

    Abstract The excitability of rat sympathetic neurons and integration of nicotinic EPSPs were compared in primary cell culture and in the acutely isolated intact superior cervical ganglion using whole cell patch electrode recordings. When repetitive firing was classified by Hodgkin's criteria in cultured cells, 18% displayed tonic class 1 excitability, 36% displayed adapting class 2 excitability and 46% displayed phasic class 3 excitability. In the intact ganglion, 71% of cells were class 1 and 29% were class 2. This diverges from microelectrode reports that nearly 100% of superior cervical ganglion neurons show phasic class 3 firing. The hypothesis that the disparity between patch and microelectrode data arises from a shunt conductance was tested using the dynamic clamp in cell culture. Non-depolarizing shunts of 3–10 nS converted cells from classes 1 and 2 to class 3 dynamics with current–voltage relations that replicated microelectrode data. Primary and secondary EPSPs recorded from the intact superior cervical ganglion were modelled as virtual synapses in cell culture using the dynamic clamp. Stimulating sympathetic neurons with virtual synaptic activity, designed to replicate in vivo recordings of EPSPs in muscle vasoconstrictor neurons, produced a 2.4-fold amplification of presynaptic activity. This gain in postsynaptic output did not differ between neurons displaying the three classes of excitability. Mimicry of microelectrode damage by virtual leak channels reduced and eventually obliterated synaptic gain by inhibiting summation of subthreshold EPSPs. These results provide a framework for interpreting sympathetic activity recorded from intact animals and support the hypothesis that paravertebral ganglia function as activity-dependent amplifiers of spinal output from preganglionic circuitry. PMID:25398531

  5. Sympathetic overactivity prevails over the vascular amplifier phenomena in a chronic kidney disease rat model of hypertension

    PubMed Central

    Ameer, Omar Z.; Hildreth, Cara M.; Phillips, Jacqueline K.

    2014-01-01

    Abstract We examined whether increased sympathetic nerve activity (SNA) accounts for enhanced depressor responses to ganglionic blockade in the Lewis polycystic kidney (LPK) model of chronic kidney disease (CKD) or whether it reflects increased vascular responses to vasodilation (vascular amplifier). Under urethane anesthesia, depressor responses to ganglionic blockade (hexamethonium, 0.5–40 mg/kg i.v.), and direct vasodilation (sodium nitroprusside [SNP], 2.5–40 μg/kg i.v. and adenosine, 3–300 μg/kg i.v.) were compared in the LPK with normotensive Lewis and spontaneously hypertensive rats (SHR) (total n = 37). Hexamethonium (8 mg/kg) produced a greater depressor response in the LPK (−51 ± 3 mmHg) compared with Lewis (−31 ± 3 mmHg, P <0.05) but not SHR (−46 ± 3 mmHg). In LPK, the ratio of the hexamethonium/vasodilator MAP responses was greater when compared with Lewis (hexamethonium/SNP 1.34 ± 0.1 vs. 0.9 ± 0.09 and hexamethonium/adenosine: 2.28 ± 0.3 vs. 1.16 ± 0.1, both P <0.05) but not SHR. Results for systolic blood pressure (SBP) were comparable. The slope of the relationship between the fall in SBP induced by hexamethonium and normalized low frequency (LFnu) power was also greater in the LPK (17.93 ± 3.26 mmHg/LFnu) compared with Lewis (2.78 ± 0.59 mmHg/LFnu, P =0.001) and SHR (3.36 ±0.72 mmHg/LFnu, P =0.003). These results indicate that in the LPK, sympathetic activity predominates over any vascular amplifier effect, supporting increased sympathetic vasomotor tone as a major contributor to hypertension in this model of CKD. PMID:25413325

  6. Gastrointestinal Intervention Ameliorates High Blood Pressure Through Antagonizing Overdrive of the Sympathetic Nerve in Hypertensive Patients and Rats

    PubMed Central

    Zhang, Hexuan; Pu, Yunfei; Chen, Jing; Tong, Weidong; Cui, Yuanting; Sun, Fang; Zheng, Zhou; Li, Qiang; Yang, Tao; Meng, Changyuan; Lu, Zongshi; Li, Li; Yan, Zhencheng; Liu, Daoyan; Zhu, Zhiming

    2014-01-01

    Background We investigated the hypothesis that the favorable effects of gastrointestinal (GI) intervention on hypertension (HTN) and cardiovascular (CV) disturbances are mediated by antagonizing overdrive of the sympathetic nervous system (SNS). Methods and Results Hypertensive patients with metabolic disturbances underwent laparoscopic Roux‐en‐Y gastric bypass surgery, and spontaneously hypertensive rats (SHRs) underwent RYGB or sham surgery. Blood pressure (BP), heart rate (HR), endothelium‐dependent flow‐mediated dilation, and anthropometric as well as laboratory parameters were measured at baseline and during follow‐up. Changes of BP and HR in response to cold stress, renal sympathetic nervous activity (RSNA), vasoconstriction induced by electrical field stimulation, microinjection of nucleus of the solitary tract (NTS), and CV function and structure were examined in SHRs with or without surgery. Compared with baseline, BP and HR were significantly reduced in both hypertensive patients with type 2 diabetes and rats. Impaired endothelial‐dependent vasodilatation and metabolic disturbances in hypertensive patients were also ameliorated after surgery. CV disturbances were reversed by surgery in SHRs. Under acute cold exposure, the variations in BP and HR were smaller in surgically treated SHRs, compared to sham SHRs. RSNA and vasoconstriction induced by perivascular nerve stimulation as well as NTS‐mediated changes of BP were decreased in surgically treated SHRs, compared to sham SHR. Weight loss did not affect BP and RSNA in sham SHRs. Conclusions GI intervention ameliorates HTN in both hypertensive patients and rats by inhibiting overdrive of the SNS. Therefore, targeting gastrointestine could be a novel strategy to treat HTN with metabolic disturbances. PMID:25240055

  7. Activation and integration of bilateral GABA-mediated synaptic inputs in neonatal rat sympathetic preganglionic neurones in vitro

    PubMed Central

    Whyment, Andrew D; Wilson, Jennifer M M; Renaud, Leo P; Spanswick, David

    2004-01-01

    The role of GABA receptors in synaptic transmission to neonatal rat sympathetic preganglionic neurones (SPNs) was investigated utilizing whole-cell patch clamp recording techniques in longitudinal and transverse spinal cord slice preparations. In the presence of glutamate receptor antagonists (NBQX, 5 μm and D-APV, 10 μm), electrical stimulation of the ipsilateral or contralateral lateral funiculi (iLF and cLF, respectively) revealed monosynaptic inhibitory postsynaptic potentials (IPSPs) in 75% and 65% of SPNs, respectively. IPSPs were sensitive to bicuculline (10 μm) in all neurones tested and reversed polarity around −55 mV, the latter indicating mediation via chloride conductances. In three neurones IPSPs evoked by stimulation of the iLF (n = 1) or cLF (n = 2) were partly sensitive to strychnine (2 μm). The expression of postsynaptic GABAA and GABAB receptors were confirmed by the sensitivity of SPNs to agonists, GABA (2 mm), muscimol (10–100 μm) or baclofen (10–100 μm), in the presence of TTX, each of which produced membrane hyperpolarization in all SPNs tested. Muscimol-induced responses were sensitive to bicuculline (1–10 μm) and SR95531 (10 μm) and baclofen-induced responses were sensitive to 2-hydroxy-saclofen (100–200 μm) and CGP55845 (200 nm). The GABAC receptor agonist CACA (200 μm) was without significant effect on SPNs. These results suggest that SPNs possess postsynaptic GABAA and GABAB receptors and that subsets of SPNs receive bilateral GABAergic inputs which activate GABAA receptors, coupled to a chloride conductance. At resting or holding potentials close to threshold either single or bursts (10–100 Hz) of IPSPs gave rise to a rebound excitation and action potential firing at the termination of the burst. This effect was mimicked by injection of small (10–20 pA) rectangular-wave current pulses, which revealed a time-dependent, Cs+-sensitive inward rectification and rebound excitation at the termination of the response to

  8. Differential action for ethanol on baroreceptor reflex control of heart rate and sympathetic efferent discharge in rats

    SciTech Connect

    Xin, Z.; Abdel-Rahman, A.R.A.; Wooles, W.R.

    1988-01-01

    The acute effects of ethanol (0.33, 0.66, or 1 g/kg) on baroreflex control of heart rate (HR) and sympathetic efferent discharge (SED) were investigated in rats. The two higher doses of ethanol caused a progressive and significant increase in baseline SED and a slight increase in HR. The findings suggest that the sensitivity of the reflex control of SED was preserved whereas that of HR was impaired after acute ethanol administration. Since these findings were obtained in the same animals, the data suggest that acute ethanol has a differential action on reflex control of SED and HR. Further, the significant increase in SED after moderate and high doses of ethanol suggests an increased central sympathetic tone as recordings were made from preganglionic nerve fibers (splanchnic nerve). The absence of an increase in baseline MAP, in spite of a significant increase in baseline SED following acute ethanol injection, could be explained, at least in part, by an ethanol-evoked reduction in pressor responsiveness to phenylephrine, an ..cap alpha..-adrenergic agonist.

  9. Colocalisation of insulin and IGF-1 receptors in cultured rat sensory and sympathetic ganglion cells

    PubMed Central

    KARAGIANNIS, S. N.; KING, R. H. M.; THOMAS, P. K.

    1997-01-01

    Peripheral sensory and autonomic neurons are known to possess insulin receptors. These have been considered to be of the peripheral type, i.e. similar to those of hepatic and fat cells rather than of the brain type which show dual specificity for both insulin and insulin-like growth factor (IGF-1). We have examined the localisation of insulin and IGF-1 receptors in cultured sensory and sympathetic ganglion cells using confocal microscopy and indirect labelling with FITC (fluorescein isothiocyanate) and TRITC (tetramethyl rhodamine isothiocyanate) respectively. We have shown that in cultured U266B1 multiple myeloma cells these receptors display separate localisation, whereas they are colocalised in IM-9 lymphocytes which are known to possess hybrid receptors. We have confirmed the sequestration of insulin and IGF-1 receptors in the cytoplasm of sensory and sympathetic neurons, consistent with a brain-type receptor. The colocalisation of insulin and IGF-1 receptors in sensory and sympathetic ganglion cells is consistent with the view that they are hybrid receptors, similar to those present in the CNS. The function of these receptors, as suggested for the CNS, may be related to trophic support for neurons. PMID:9419000

  10. 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

  11. BETA ADRENERGIC CONTROL OF MACROMOLECULE SYNTHESIS IN NEONATAL RAT HEART, KIDNEY AND LUNG: RELATIONSHIP TO SYMPATHETIC NEURONAL DEVELOPMENT

    EPA Science Inventory

    The sympathetic nervous system has been hypothesized to coordinate the timing of cellular development in peripheral tissues. n the current study, we evaluated the relationships among the ontogeny of sympathetic projections to peripheral organs, the patterns of macromolecule synth...

  12. 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

  13. 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

  14. Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs

    PubMed Central

    Zheng, Xiaoxin; Li, Xiaoyan; Lyu, Yongnan; He, Yiyu; Wan, Weiguo; Jiang, Xuejun

    2016-01-01

    Background The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. Material/Methods MI and RSD were induced in Sprague–Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. Results In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. Conclusions The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21. PMID:27490896

  15. Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs.

    PubMed

    Zheng, Xiaoxin; Li, Xiaoyan; Lyu, Yongnan; He, Yiyu; Wan, Weiguo; Jiang, Xuejun

    2016-01-01

    BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. RESULTS In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. CONCLUSIONS The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21. PMID:27490896

  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. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

    SciTech Connect

    DiCicco-Bloom, E.; Black, I.B. )

    1988-06-01

    While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating ({sup 3}H)thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of ({sup 3}H)thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain.

  18. 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

  19. 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.

  20. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries

    PubMed Central

    Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Arribas, Silvia M.; González, Maria Carmen; Fresco, Paula; Diniz, Carmen

    2015-01-01

    Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation. PMID:26075386

  1. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

    PubMed

    Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Arribas, Silvia M; González, Maria Carmen; Fresco, Paula; Diniz, Carmen

    2015-01-01

    Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation. PMID:26075386

  2. Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic premotor neurons in the in situ arterially perfused preparation of rats.

    PubMed

    Koganezawa, Tadachika; Paton, Julian F R

    2014-11-01

    Brainstem hypoperfusion is a major excitant of sympathetic activity triggering hypertension, but the exact mechanisms involved remain incompletely understood. A major source of excitatory drive to preganglionic sympathetic neurons originates from the ongoing activity of premotor neurons in the rostral ventrolateral medulla (RVLM sympathetic premotor neurons). The chemosensitivity profile of physiologically characterized RVLM sympathetic premotor neurons during hypoxia and hypercapnia remains unclear. We examined whether physiologically characterized RVLM sympathetic premotor neurons can sense brainstem ischaemia intrinsically. We addressed this issue in a unique in situ arterially perfused preparation before and after a complete blockade of fast excitatory and inhibitory synaptic transmission. During hypercapnic hypoxia, respiratory modulation of RVLM sympathetic premotor neurons was lost, but tonic firing of most RVLM sympathetic premotor neurons was elevated. After blockade of fast excitatory and inhibitory synaptic transmission, RVLM sympathetic premotor neurons continued to fire and exhibited an excitatory firing response to hypoxia but not hypercapnia. This study suggests that RVLM sympathetic premotor neurons can sustain high levels of neuronal discharge when oxygen is scarce. The intrinsic ability of RVLM sympathetic premotor neurons to maintain responsivity to brainstem hypoxia is an important mechanism ensuring adequate arterial pressure, essential for maintaining cerebral perfusion in the face of depressed ventilation and/or high cerebral vascular resistance. PMID:25016023

  3. Effects of arachidonic acid on unitary calcium currents in rat sympathetic neurons

    PubMed Central

    Liu, Liwang; Rittenhouse, Ann R

    2000-01-01

    We have characterized the actions of arachidonic acid (AA) on whole cell and unitary calcium (Ca2+) currents in rat neonatal superior cervical ganglion (SCG) neurons using barium (Ba2+) as the charge carrier. Whole cell currents were elicited by stepping the membrane potential from −90 mV to +10 mV. Arachidonic acid (5 μm) was introduced into the bath in the continued presence of 1 μm (+)-202-791, an L-type Ca2+ channel agonist. Under these conditions, the peak current, comprised mainly of N-type current, and a slow, (+)-202-791-induced component of the tail current were inhibited by 67 ± 6 and 60 ± 10%, respectively, indicating that AA inhibits both N- and L-type currents. At a test potential of +30 mV, AA (5 μm) decreased unitary L- and N-type Ca2+ channel open probability (Po) in cell-attached patches that contained a single channel. For both channels, the underlying causes of the decrease in Po were similar. Arachidonic acid caused an increase in the percentage of null sweeps and in the number of null sweeps that clustered together. In sweeps with activity, the average number of openings per sweep decreased, while first latency and mean closed time increased. Arachidonic acid had no significant effect on unitary current amplitude or mean open time. Our findings are the first description of the inhibition of unitary L- and N-type Ca2+ channel activity by AA and are consistent with both channels spending more time in their null mode and with increased dwell time in one or more closed states. PMID:10835042

  4. Targeted NGF siRNA Delivery Attenuates Sympathetic Nerve Sprouting and Deteriorates Cardiac Dysfunction in Rats with Myocardial Infarction

    PubMed Central

    Wang, Ye; Xue, Mei; Suo, Fei; Li, Xiaolu; Cheng, Wenjuan; Li, Xinran; Yin, Jie; Liu, Ju; Yan, Suhua

    2014-01-01

    Nerve growth factor (NGF) is involved in nerve sprouting, hyper-innervation, angiogenesis, anti-apoptosis, and preservation of cardiac function after myocardial infarction (MI). Positively modulating NGF expression may represent a novel pharmacological strategy to improve post-infarction prognosis. In this study, lentivirus encoding NGF short interfering RNA (siRNA) was prepared, and MI was modeled in the rat using left anterior descending coronary artery ligation. Rats were randomly grouped to receive intramyocardial injection of lentiviral solution containing NGF-siRNA (n = 19, MI-SiNGF group), lentiviral solution containing empty vector (n = 18, MI-GFP group) or 0.9% NaCl solution (n = 18, MI-control group), or to receive thoracotomy and pericardiotomy (n = 17, sham-operated group). At 1, 2, 4, and 8 wk after transduction, rats in the MI-control group had higher levels of NGF mRNA and protein than those in the sham-operated group, rats in the MI-GFP group showed similar levels as the MI-control group, and rats in the MI-SiNGF group had lower levels compared to the MI-GFP group, indicating that MI model was successfully established and NGF siRNA effectively inhibited the expression of NGF. At 8 wk, echocardiographic and hemodynamic studies revealed a more severe cardiac dysfunction in the MI-siRNA group compared to the MI-GFP group. Moreover, rats in the MI-siRNA group had lower mRNA and protein expression levels of tyrosine hydroxylase (TH) and growth-associated protein 43-positive nerve fibers (GAP-43) at both the infarcted border and within the non-infarcted left ventricles (LV). NGF silencing also reduced the vascular endothelial growth factor (VEGF) expression and decreased the arteriolar and capillary densities at the infarcted border compared to the MI-GFP group. Histological analysis indicated a large infarcted size in the MI-SiNGF group. These findings suggested that endogenous NGF silencing attenuated sympathetic nerve sprouting and

  5. Stimulation of sympathetic innervation in the upper gastrointestinal tract as a treatment for obesity

    PubMed Central

    Zheng, Jolene; DiLorenzo, Daniel J.; McLaughlin, Leslie; Roberts, Andrew T.; Greenway, Frank L.

    2009-01-01

    SUMMARY Sympathetic activity and obesity have a reciprocal relationship. Firstly, hypothalamic obesity is associated with decreased sympathetic activity. Caffeine and ephedrine increase sympathetic activity and induce weight loss, of which 25% is due to increased metabolic rate and 75% is due to a reciprocally decreased food intake. Secondly, hormones and drugs that affect body weight have an inverse relationship between food intake and metabolic rate. Neuropeptide Y decreases sympathetic activity and increases food intake and body weight. Thirdly, a gastric pacemaker Transcend® and vagotomy increase the ratio of sympathetic to parasympathetic activation, decrease food intake, and block gut satiety hormones. Weight loss with the pacemaker or vagotomy is variable. Significant weight reduction is seen only in a small group of those treated. This suggests that activation of the sympathetic arm of the autonomic nervous system may be most important for weight loss. Systemic sympathetic activation causes weight loss in obese patients, but side effects limited its use. We hypothesize that selective local electrical sympathetic stimulation of the upper gastrointestinal tract may induce weight loss and offer a safer, yet effective, obesity treatment. Celiac ganglia delivers sympathetic innervation to the upper gastrointestinal tract. Voltage regulated electrical simulation of the rat celiac ganglia increased metabolic rate in a dose-dependent manner. Stimulation of 6, 3, or 1.5 V increased metabolic rate 15.6%, 6.2%, and 5%, respectively in a single rat. These responses support our hypothesis that selective sympathetic stimulation of the upper GI tract may treat obesity while avoiding side effects of systemic sympathetic activation. PMID:19246162

  6. The α2-adrenoceptors mediating inhibition of the vasopressor sympathetic outflow in pithed rats: pharmacological correlation with α2A, α2B and α2C subtypes.

    PubMed

    Villamil-Hernández, Ma Trinidad; Alcántara-Vázquez, Oscar; Sánchez-López, Araceli; Centurión, David

    2013-10-15

    α2-Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In vitro studies have confirmed that α2A, α2B and α2C subtypes inhibited noradrenaline release from postganglionic sympathetic neurons but no study has been reported their involvement in the vasopressor sympathetic outflow in vivo. Thus, this study analysed the subtype(s) involved in the inhibition produced by the α2-adrenoceptor agonist, B-HT 933, on the vasopressor sympathetic outflow. Male Wistar pithed rats were pre-treated with i.v. bolus injections of gallamine (25mg/kg) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9) or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or exogenous noradrenaline produced, respectively, frequency-dependent and dose-dependent vasopressor responses. I.v. continuous infusion of B-HT 933 (30 μg/kg min) failed to modify the vasopressor responses to exogenous noradrenaline and inhibited those induced by preganglionic stimulation of the vasopressor sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii) partially antagonised by BRL44408 (300 μg/kg; α2A), imiloxan (3000 μg/kg; α2B) and/or JP-1302 (300 μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300 μg/kg) or the combination of BRL44408 (300 μg/kg)+imiloxan (3000 μg/kg)+JP-1302 (300 μg/kg). The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. These results suggest that the vasopressor sympatho-inhibition to B-HT 933 is primarily mediated by activation of α2A/2B/2C-adrenoceptors in pithed rats. PMID:24028939

  7. Role of brainstem thyrotropin-releasing hormone-triggered sympathetic overactivation in cardiovascular mortality in type 2 diabetic Goto-Kakizaki rats.

    PubMed

    Yang, Hong; Nyby, Michael D; Ao, Yan; Chen, Ai; Adelson, David W; Smutko, Victoria; Wijesuriya, Janake; Go, Vay Liang W; Tuck, Michael L

    2012-02-01

    Sympathetic hyperactivity has an important role in cardiovascular mortality in patients with type 2 diabetes (T2D). Thyrotropin-releasing hormone (TRH)-containing fibers innervate autonomic motor and premotor nuclei of the brainstem and spinal cord that regulate cardiovascular functions. We compared cardiovascular responses to application of TRH-analog in the brainstem of Wistar and T2D Goto-Kakizaki (GK) rats. GK rats exhibited basal systolic hypertension (152±2 mm Hg) and had a significantly potentiated, dose-related hypertensive response to intracisternal (i.c.) injection of the TRH-analog RX77368 (10-60 ng). In GK rats only, i.c. RX77368 (30-60 ng) markedly increased heart rate (HR; +88 b.p.m.) and induced acute cardiac mortality (100%), concurrent with extreme hyperglycemia (>26 mmol l(-1)), increased plasma H(2)O(2) and 8-isoprostane, and enhanced heart expression of NADPH oxidase 4 and vascular cell adhesion molecule-1 mRNAs. GK rats also had elevated basal plasma epinephrine, higher adrenal gene expression of tyrosine hydroxylase and dopamine β-hydroxylase (DβH), and greater plasma catecholamine and adrenal DβH responses to i.c. TRH-analog, compared with Wistar rats. In GK rats, hexamethonium blocked i.c. RX77368-induced hypertensive and tachycardic responses, and reduced mortality by 86%, whereas phentolamine abolished the hypertensive response but enhanced tachycardia (+160 b.p.m.), and reduced mortality by 50%. The angiotensin II type 1 receptor antagonist irbesartan prevented i.c. RX77368-induced increases in blood pressure, HR and mortality. In conclusion, sympathetic overactivation triggered by brainstem TRH contributes to the mechanism of cardiovascular morbidity and mortality in T2D, which involves heightened cardiac inflammation and peripheral oxidative stress responses to sympathetic drive, and a mediating role of the renin-angiotensin system. PMID:21900943

  8. Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats.

    PubMed

    Samuelsson, Anne-Maj; Morris, Abigail; Igosheva, Natalia; Kirk, Shona L; Pombo, Joaquim M C; Coen, Clive W; Poston, Lucilla; Taylor, Paul D

    2010-01-01

    Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension in adult offspring. In this study we investigated the influence of maternal obesity in the rat on blood pressure and blood pressure regulatory pathways in juvenile and adult offspring. Obesity was induced before pregnancy in female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. In juvenile animals (30 days of age), before the onset of obesity and hyperleptinemia, basal nighttime mean arterial pressure was significantly raised in the offspring of obese dams (OffOb) relative to offspring of controls (OffCon; mean arterial pressure, males: OffOb, 121.8+/-0.6 mm Hg versus OffCon, 115.0+/-0.5 mm Hg, n=6, P<0.01; females: OffOb, 125.4+/-0.4 mm Hg versus OffCon, 114.4+/-0.5 mm Hg, n=6, P<0.001), as was the mean arterial pressure response to restraint stress (P<0.01). The pressor response to a leptin challenge was enhanced in OffOb rats (Deltamean arterial pressure: OffOb, 9.7+/-0.8 mm Hg versus OffCon, 5.3+/-1.3 mm Hg; n=8; P<0.05). Renal tissue norepinephrine content (P<0.001) and renin expression (P<0.05) were markedly raised. Analysis of heart rate variability revealed an increased low:high frequency ratio in OffOb versus OffCon rats (P<0.05). At 90 days, hypertension in OffOb rats persisted and was abolished by alpha1- and beta-adrenergic blockade, and cardiovascular responses to phenylephrine or sodium nitroprusside indicated altered baroreceptor function. The exaggerated pressor response to leptin in OffOb rats was maintained. Hypertension in the offspring of obese rats may arise from persistent sympathoexcitatory hyperresponsiveness acquired in early stages of development. PMID:19901159

  9. Use-dependent loss of active sympathetic neurogenic vasodilation after nitric oxide synthase inhibition in conscious rats. Evidence for the presence of preformed stores of nitric oxide-containing factors

    NASA Technical Reports Server (NTRS)

    Davisson, R. L.; Shaffer, R. A.; Johnson, A. K.; Lewis, S. J.

    1996-01-01

    In this study, we examined whether air-jet stress-induced active sympathetic hindlimb vasodilation in conscious rats involves the release of preformed stores of nitric oxide-containing factors. We determined the effects of repeated episodes of air-jet stress (six episodes given 5 minutes apart) on mean arterial pressure and vascular resistances in the mesenteric bed and intact and sympathetically denervated hindlimb beds of conscious rats treated with saline or the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg IV). In saline-treated rats, air-jet stress produced alerting behavior, minor changes in blood pressure, pronounced mesenteric vaso-constriction, and immediate and marked vasodilation in the sympathetically intact hindlimb but a minor vasodilation in the sympathetically denervated hindlimb. Each air-jet stress produced virtually identical responses. In L-NAME-treated rats, the first air-jet stress produced vasodilator responses in the sympathetically intact and sympathetically denervated hindlimbs that were similar to those in the saline-treated rats. However, each subsequent air-jet stress produced progressively smaller vasodilator responses in the sympathetically intact but not the sympathetically denervated hindlimb. There was no loss of air-jet stress-induced alerting behavior or mesenteric vasoconstriction, suggesting that L-NAME did not interfere with the central processing of the air-jet or the resultant changes in autonomic nerve activity. The progressive diminution of air-jet stress-induced vasodilation in the intact hindlimb of L-NAME-treated rats may be due to the use-dependent depletion of preformed stores of nitric oxide-containing factors that cannot be replenished in the absence of nitric oxide synthesis.

  10. Inhibition of Notch signaling pathway attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats post-myocardial infarction.

    PubMed

    Yin, Jie; Hu, Hesheng; Li, Xiaolu; Xue, Mei; Cheng, Wenjuan; Wang, Ye; Xuan, Yongli; Li, Xinran; Yang, Na; Shi, Yugen; Yan, Suhua

    2016-01-01

    Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although being a key immune mediator, the role of Notch has yet to be explored. We investigated whether Notch regulates macrophage responses to inflammation and affects cardiac sympathetic reinnervation in rats undergoing MI. MI was induced by coronary artery ligation. A high level of Notch intracellular domain was observed in the macrophages that infiltrated the infarct area at 3 days post-MI. The administration of the Notch inhibitor N-N-(3,5-difluorophenacetyl-L-alanyl)-S-phenylglycine-t-butyl ester (DAPT) (intravenously 30 min before MI and then daily until death) decreased the number of macrophages and significantly increased the M2 macrophage activation profile in the early stages and attenuated the expression of nerve growth factor (NGF). Eventually, NGF-induced sympathetic hyperinnervation was blunted, as assessed by the immunofluorescence of tyrosine hydroxylase. At 7 days post-MI, the arrhythmia score of programmed electric stimulation in the vehicle-treated infarcted rats was higher than that in rats treated with DAPT. Further deterioration in cardiac function and decreases in the plasma levels of TNF-α and IL-1β were also detected. In vitro studies revealed that LPS/IFN-γ upregulated the surface expression of NGF in M1 macrophages in a Notch-dependent manner. We concluded that Notch inhibition during the acute inflammatory response phase is associated with the downregulation of NGF, probably through a macrophage-dependent pathway, thus preventing the process of sympathetic hyperinnervation. PMID:26491050

  11. 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. PMID:27070752

  12. Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations.

    PubMed

    Sastre, Esther; Caracuel, Laura; Prieto, Isabel; Llévenes, Pablo; Aller, M Ángeles; Arias, Jaime; Balfagón, Gloria; Blanco-Rivero, Javier

    2016-01-01

    We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis. PMID:27484028

  13. Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations

    PubMed Central

    Sastre, Esther; Caracuel, Laura; Prieto, Isabel; Llévenes, Pablo; Aller, M. Ángeles; Arias, Jaime; Balfagón, Gloria; Blanco-Rivero, Javier

    2016-01-01

    We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis. PMID:27484028

  14. The effects of various carbohydrates on sympathetic activity in heart and interscapular brown adipose tissue of the rat.

    PubMed

    Walgren, M C; Young, J B; Kaufman, L N; Landsberg, L

    1987-06-01

    The present studies were undertaken to determine the effect of various carbohydrates on sympathetic nervous system (SNS) activity. Tritiated-norepinephrine (3H-NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed either chow or chow plus 50% caloric supplements of fructose, sucrose, dextrose, or corn starch. Additional studies were performed to examine whether absorption of carbohydrate plays a role in the SNS response, and to determine whether sweet taste in the form of artificial sweeteners may influence SNS activity. After five to ten days on the respective diets, 3H-NE turnover was increased to a similar extent by all carbohydrates tested (from 38% to 160% greater than controls in different studies). Addition of acarbose (which impairs sucrose absorption) to a sucrose-supplemented diet abolished the SNS stimulatory response, whereas cholestyramine (a drug that blocks fat absorption) had no effect. Finally, the addition of saccharin or aspartame to a chow diet failed to alter SNS activity. Thus, caloric supplementation with several carbohydrates, in addition to sucrose, stimulates both cardiac and IBAT SNS activity, absorption of carbohydrate is required for this effect, and noncaloric sugar substitutes do not alter SNS function. PMID:3587017

  15. Local knockdown of the NaV1.6 sodium channel reduces pain behaviors, sensory neuron excitability, and sympathetic sprouting in rat models of neuropathic pain.

    PubMed

    Xie, W; Strong, J A; Zhang, J-M

    2015-04-16

    In the spinal nerve ligation (SNL) model of neuropathic pain, as in other pain models, abnormal spontaneous activity of myelinated sensory neurons occurs early and is essential for establishing pain behaviors and other pathologies. Sympathetic sprouting into the dorsal root ganglion (DRG) is observed after SNL, and sympathectomy reduces pain behavior. Sprouting and spontaneous activity may be mutually reinforcing: blocking neuronal activity reduces sympathetic sprouting, and sympathetic spouts functionally increase spontaneous activity in vitro. However, most studies in this field have used nonspecific methods to block spontaneous activity, methods that also block evoked and normal activity. In this study, we injected small inhibitory (si) RNA directed against the NaV1.6 sodium channel isoform into the DRG before SNL. This isoform can mediate high-frequency repetitive firing, like that seen in spontaneously active neurons. Local knockdown of NaV1.6 markedly reduced mechanical pain behaviors induced by SNL, reduced sympathetic sprouting into the ligated sensory ganglion, and blocked abnormal spontaneous activity and other measures of hyperexcitability in myelinated neurons in the ligated sensory ganglion. Immunohistochemical experiments showed that sympathetic sprouting preferentially targeted NaV1.6-positive neurons. Under these experimental conditions, NaV1.6 knockdown did not prevent or strongly alter single evoked action potentials, unlike previous less specific methods used to block spontaneous activity. NaV1.6 knockdown also reduced pain behaviors in another pain model, chronic constriction of the sciatic nerve, provided the model was modified so that the lesion site was relatively close to the siRNA-injected lumbar DRGs. The results highlight the relative importance of abnormal spontaneous activity in establishing both pain behaviors and sympathetic sprouting, and suggest that the NaV1.6 isoform may have value as a therapeutic target. PMID:25686526

  16. Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats.

    PubMed

    Centurión, David; De la Cruz, Saúl Huerta; Gutiérrez-Lara, Erika J; Beltrán-Ornelas, Jesús H; Sánchez-López, Araceli

    2016-01-01

    It has been reported that i.v. administration of NaHS, a donor of H2S, elicited dose-dependent hypotension although the mechanisms are not completely understood. In this regard, several mechanisms could be involved including the inhibition of the vasopressor sympathetic outflow. Thus, this study was designed to determine the potential capability of NaHS to mediate inhibition of the vasopressor responses induced by preganglionic sympathetic stimulation. For this purpose, Wistar rats were anaesthetised, pithed and cannulated for drug administration. In animals pre-treated with gallamine, the effect of i.v. infusion of NaHS (310 and 560μg/kgmin) or its vehicle (phosphate buffer) was determined on the vasopressor responses induced by: (1) sympathetic stimulation (0.03-10Hz); (2) i.v. bolus injections of exogenous noradrenaline (0.03-3μg/kg); or (3) methoxamine (1-100μg/kg). The vasopressor responses induced by preganglionic sympathetic stimulation were dose-dependently inhibited by i.v. infusion of NaHS (310 and 560μg/kgmin), but not by vehicle, particularly at high frequencies. In marked contrast, the vasopressor responses to exogenous noradrenaline or methoxamine were not inhibited by the above doses of NaHS or its vehicle. The above results, taken together, demonstrate that NaHS inhibited the vasopressor responses induced by preganglionic sympathetic outflow by a prejunctional mechanism. This is the first evidence demonstrating this effect by NaHS that may contribute, at least in part, to the hypotension induced by NaHS. PMID:26643171

  17. Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system.

    PubMed

    Maranon, Rodrigo O; Reckelhoff, Jane F

    2016-02-01

    Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P < 0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142 ± 10 vs. 161 ± 6 mm Hg; P < 0.05 vs. RD, P < 0.05 vs. baseline). However, female SHR rats remained significantly hypertensive despite both pharmacological intervention and RD. The data suggest that both the renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women. PMID:26811052

  18. Physiological regulation of pro-inflammatory cytokines expression in rat cardiovascular tissues by sympathetic nervous system and angiotensin II.

    PubMed

    Dab, Houcine; Hachani, Rafik; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

    2013-12-01

    Pro-inflammatory cytokines regulation by sympathetic nervous system (SNS) and angiotensin II (ANG II) was widely described in cardiovascular system, but the role of such neuro-humoral interaction needs further investigation in this context. We tested SNS-ANG II interaction on IL-6 and TNF-α mRNA expression in left ventricle and aorta from normotensive rats by sympathectomy with guanethidine and blockade of the ANG II AT1 receptors (AT1R) antagonist with losartan. mRNA synthesis of IL-6 and TNF-α were performed by Q-RT-PCR. In the left ventricle, IL-6 mRNA increased by 63% (p < 0.01) after sympathectomy, still unchanged after losartan treatment and decreased by 38% (p < 0.05) after combined treatment. TNF-α mRNA decreased by 44% (p < 0.01), only after combined treatment. In the aorta, IL-6 mRNA increased equally by 65% (p < 0.05) after sympathectomy or losartan treatment. TNF-α mRNA decreased by 28, 41, and 42% (p < 0.05) after sympathectomy, losartan and combined treatments, respectively. Our data suggest that ANG II stimulates directly (via AT1R) and indirectly (via SNS) IL-6 mRNA synthesis in left ventricle and aorta and TNF-α mRNA in left ventricle. ANG II seems unable to influence directly TNF-α mRNA synthesis in the aorta but can stimulate this cytokine via SNS. The results are relevant to prevent or reduce proinflammatory cytokines overexpression seen in cardiovascular diseases. PMID:23846262

  19. 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

  20. Characterization of the hyperpolarization-activated chloride current in dissociated rat sympathetic neurons.

    PubMed

    Clark, S; Jordt, S E; Jentsch, T J; Mathie, A

    1998-02-01

    1. Dissociated rat superior cervical ganglion (SCG) neurons have been shown to possess a hyperpolarization-activated inwardly rectifying chloride current. The current was not altered by changes in external potassium concentration, replacing external cations with NMDG (N-methyl-D-glucamine) or by addition of 10 mM caesium or barium ions. 2. The reversal potential of the current was altered by changing external anions. The anion selectivity of the current was Cl- > Br- > I- > cyclamate. All substituted permeant anions also blocked the current. 3. The current was blocked by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid), 9AC (anthracene-9-carboxylic acid) and NPPB (5-nitro-2-(3-phenylpropylamino)benzoic acid) but was unaffected by SITS (4-acetamido-4'-isothiocyanatostilbene- 2,2'-disulphonic acid) and niflumic acid. The effective blockers were voltage dependent; DIDS and NPPB were more effective at depolarized potentials while 9AC was more effective at hyperpolarized potentials. 4. The current was enhanced by extracellular acidification and reduced by extracellular alkalinization. Reducing external osmolarity was without effect in conventional whole-cell recording but enhanced current amplitude in those perforated-patch recordings where little current was evident in control external solution. 5. The current in SCG neurons was blocked by external cadmium and zinc. ClC-2 chloride currents expressed in Xenopus oocytes were also sensitive to block by these divalent ions and by DIDS but the sensitivity of ClC-2 to block by cadmium ions was lower than that of the current in SCG neurons. 6. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments showed the presence of mRNA for ClC-2 in SCG neurons but not in rat cerebellar granule cells which do not possess a hyperpolarization-activated Cl- current. 7. The data suggest that ClC-2 may be functionally expressed in rat SCG neurons. This current may play a role in regulating the internal chloride

  1. A single oral dose of flavan-3-ols enhances energy expenditure by sympathetic nerve stimulation in mice.

    PubMed

    Kamio, Naoya; Suzuki, Takuma; Watanabe, Yuto; Suhara, Yoshitomo; Osakabe, Naomi

    2016-02-01

    Numerous clinical studies have found that ingestion of chocolate reduces the risk of metabolic syndrome, however, the mechanisms were remain unclear. We have reported that a single dose of a flavan-3-ol fraction derived from cocoa (FL) enhanced energy expenditure (EE) and increased the mRNA expression levels of uncoupling proteins (UCPs) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and the protein level of phosphorylated AMP-activated protein kinase (AMPK)α in tissues, along with plasma adrenaline level. In the present study, we examined whether the EE enhancing activity of FL is mediated by adrenergic effect using several adrenalin receptor (AR) blockers. In the first study, mice were butoxamine, as β2AR blocker, with vehicle or 10mg/kg FL orally. We found that pretreatment with butoxamine prevented the increases of EE, the mRNA expression of UCP-3, and phosphorylated AMPKα that were induced in the gastrocnemius muscle of mice by 10mg/kg FL. Secondly, mice were given SR52930, as β3AR blocker. Pretreatment with SR52930 prevented the increases of EE, the mRNA expression of UCP-3, and phosphorylated AMPKα that were induced in the gastrocnemius muscle of mice by 10mg/kg FL. Pretreatment with a combination of both blockers also reduced the increments in mRNA expression levels of UCPs and PGC-1α, however, phosphorylated AMPKα in skeletal muscle was rather increased. These results suggest that the ability of a single oral dose of FL to enhance metabolic activity is mediated by sympathetic nerve system (SNS). PMID:26738802

  2. Activity of the sympathetic-adrenomedullary system in rats after space flight on the COSMOS biosatellites

    NASA Astrophysics Data System (ADS)

    Kvetňanský, R.; Vigaš, M.; Németh, Š.; Macho, L.; Tigranyan, R. A.

    The indicators of adrenomedullary activity (catecholamine content (CA) and the activity of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH)) were measured in the adrenal glands of rats living in a state of weightlessness for 18.5-19.5 days on board the biosatellites COSMOS 936 and COSMOS 1129. None of these indicators was significantly changed by space flight, neither in the group living in a state of weightlessness nor in the group living in a centrifuge on board the spacecraft and exposed to artificial gravity of 1 g (COSMOS 936). Animals exposed after space flight to repeated immobilization stress on Earth showed a significant decrease of adrenal adrenaline and an appreciable increase in adrenal TH activity compared to stressed animals which were not in space. These results suggest that a prolonged state of weightlessness during space flight does not by itself represent an intensive stressful stimulus for the adrenomedullary system but potentiates the response of cosmonauts to stress after return to Earth.

  3. The role of dopamine D2, but not D3 or D4, receptor subtypes, in quinpirole-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats

    PubMed Central

    Altamirano-Espinoza, A H; González-Hernández, A; Manrique-Maldonado, G; Marichal-Cancino, B A; Ruiz-Salinas, I; Villalón, C M

    2013-01-01

    Background and Purpose Quinpirole (a dopamine D2-like receptor agonist) inhibits the cardioaccelerator sympathetic outflow in pithed rats by sympathoinhibitory D2-like receptors. The present study was designed to identify pharmacologically the specific D2-like receptor subtypes (i.e. D2, D3 and D4) involved in this sympathoinhibition by quinpirole. Experimental Approach One hundred fourteen male Wistar rats were pithed, artificially ventilated with room air and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n = 102) or i.v. bolus injections of exogenous noradrenaline (n = 12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively, as previously reported by our group. Key Results I.v. continuous infusions of quinpirole (0.1–10 μg kg−1 min−1), but not of saline (0.02 mL min−1), dose-dependently inhibited the sympathetically induced tachycardic responses. Moreover, the cardiac sympathoinhibition induced by 3 μg kg−1 min−1 quinpirole (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unchanged after i.v. injections of the antagonists SB-277011-A (D3; 100–300 μg kg−1) or L-745,870 (D4; 30–100 μg kg−1); and (ii) markedly blocked and abolished by, respectively, 100 and 300 μg kg−1 of the D2 preferring receptor subtype antagonist L-741,626. These doses of antagonists, which did not affect per se the sympathetically induced tachycardic responses, were high enough to completely block their respective receptors. Conclusions and Implications The cardiac sympathoinhibition induced by 3 μg kg−1 min−1 quinpirole involves the dopamine D2 receptor subtype, with no evidence for the involvement of the D3 or D4 subtypes. This provides new evidence for understanding the modulation of the cardioaccelerator sympathetic outflow. PMID:24032529

  4. Blockade of Rostral Ventrolateral Medulla (RVLM) Bombesin Receptor Type 1 Decreases Blood Pressure and Sympathetic Activity in Anesthetized Spontaneously Hypertensive Rats

    PubMed Central

    Pinto, Izabella S.; Mourão, Aline A.; da Silva, Elaine F.; Camargo, Amanda S.; Marques, Stefanne M.; Gomes, Karina P.; Fajemiroye, James O.; da Silva Reis, Angela A.; Rebelo, Ana C. S.; Ferreira-Neto, Marcos L.; Rosa, Daniel A.; Freiria-Oliveira, André H.; Castro, Carlos H.; Colombari, Eduardo; Colugnati, Diego B.; Pedrino, Gustavo R.

    2016-01-01

    Intrathecal injection of bombesin (BBS) promoted hypertensive and sympathoexcitatory effects in normotensive (NT) rats. However, the involvement of rostral ventrolateral medulla (RVLM) in these responses is still unclear. In the present study, we investigated: (1) the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR); (2) the contribution of RVLM BBS type 1 receptors (BB1) to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v.) were instrumented to record mean arterial pressure (MAP), diaphragm (DIA) motor, and renal sympathetic nerve activity (RSNA). In NT rats and SHR, BBS (0.3 mM) nanoinjected into RVLM increased MAP (33.9 ± 6.6 and 37.1 ± 4.5 mmHg, respectively; p < 0.05) and RSNA (97.8 ± 12.9 and 84.5 ± 18.1%, respectively; p < 0.05). In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7%; p < 0.05). BB1 receptors antagonist (BIM-23127; 3 mM) reduced MAP (–19.9 ± 4.4 mmHg; p < 0.05) and RSNA (−17.7 ± 3.8%; p < 0.05) in SHR, but not in NT rats (−2.5 ± 2.8 mmHg; −2.7 ± 5.6%, respectively). These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR. PMID:27313544

  5. A HaloTag® method for assessing the retrograde axonal transport of the p75 neurotrophin receptor and other proteins in compartmented cultures of rat sympathetic neurons.

    PubMed

    Mok, Sue-Ann; Lund, Karen; Lapointe, Paul; Campenot, Robert B

    2013-03-30

    We have adapted HaloTag® (HT) technology for use in compartmented cultures of rat sympathetic neurons in order to provide a technique that can be broadly applied to studies of the retrograde transport of molecules that play roles in neurotrophin signaling. Transfected neurons expressing HT protein alone, HT protein fused to the p75 neurotrophin receptor (p75NTR) or HT protein fused to tubulin α-1B were maintained in compartmented cultures in which cell bodies and proximal axons of rat sympathetic neurons reside in proximal compartments and their distal axons extend into distal compartments. HT ligand containing a fluorescent tetramethylrhodamine (TMR) label was applied either in the distal compartments or the proximal compartments, and the transport of labeled proteins was assayed by gel fluorescence imaging and TMR immunoblot. HT protein expressed alone displayed little or no retrograde transport. HT protein fused to either the intracellular C-terminus or the extracellular N-terminus of p75NTR was retrogradely transported. The retrograde transport of p75NTR was augmented when the distal axons were provided with nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) or antibodies to BDNF. The anterograde transport of HT protein fused to the N-terminus of tubulin α-1B was also demonstrated. We conclude that retrograde transport of HT fusion proteins provides a powerful and novel approach in studies of axonal transport. PMID:23348044

  6. Maternal coordination of the daily rhythm of malate dehydrogenase activity in testes from young rats: effect of maternal sympathetic denervation of the pineal gland and administration of melatonin.

    PubMed

    Vermouth, N T; Carriazo, C S; Gallará, R V; Carpentieri, A R; Bellavía, S L

    1995-02-01

    Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of tests in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats. PMID:7750160

  7. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat.

    PubMed

    Nasimi, Ali; Kafami, Marzieh

    2016-07-01

    The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release. PMID:26820216

  8. Pharmacological evidence that 5-HT1A/1B/1D, α2-adrenoceptors and D2-like receptors mediate ergotamine-induced inhibition of the vasopressor sympathetic outflow in pithed rats.

    PubMed

    Villamil-Hernández, Ma Trinidad; Alcántara-Vázquez, Oscar; Sánchez-López, Araceli; Gutiérrez-Lara, Erika J; Centurión, David

    2014-10-01

    The sympathetic nervous system that innervates the peripheral circulation is regulated by several mechanisms/receptors. It has been reported that prejunctional 5-HT1A, 5-HT1B, 5-HT1D, D2-like receptors and α2-adrenoceptors mediate the inhibition of the vasopressor sympathetic outflow in pithed rats. In addition, ergotamine, an antimigraine drug, displays affinity at the above receptors and may explain some of its adverse/therapeutic effects. Thus, the aims of this study were to investigate in pithed rats: (i) whether ergotamine produces inhibition of the vasopressor sympathetic outflow; and (ii) the major receptors involved in this effect. For this purpose, male Wistar pithed rats were pre-treated with gallamine (25 mg/kg; i.v.) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9; 0.03-3 Hz) or to receive i.v. bolus of exogenous noradrenaline (0.03-3 µg/kg). I.v. continuous infusions of ergotamine (1 and 1.8 μg/kgmin) dose-dependently inhibited the vasopressor responses to sympathetic stimulation but not those to exogenous noradrenaline. The sympatho-inhibition elicited by 1.8 μg/kg min ergotamine was (i) unaffected by saline (1 ml/kg); (ii) partially antagonised by WAY 100635 (5-HT1A; 30 μg/kg) and rauwolscine (α2-adrenoceptor; 300 μg/kg), and (iii) dose-dependently blocked by GR 127935 (5-HT1B/1D; 100 and 300 μg/kg) or raclopride (D2-like; 300 and 1000 μg/kg), The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that ergotamine induces inhibition of the vasopressor sympathetic outflow by activation of prejunctional 5-HT1A, 5-HT1B/1D, α2-adrenoceptors and D2-like receptors in pithed rats. PMID:24975101

  9. Characterization of prejunctional 5-HT1 receptors that mediate the inhibition of pressor effects elicited by sympathetic stimulation in the pithed rat

    PubMed Central

    Morán, A; Fernández, M M; Velasco, C; Martín, M L; San Román, L

    1998-01-01

    A study was made of the effects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 μg kg−1 min−1 reduced the pressor effects obtained by electrical stimulation. The inhibitory effect of 5-CT was significantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-CT.The inhibition induced by 0.01 μg kg−1 min−1 of 5-CT on sympathetically-induced pressor responses was partially blocked after i.v. treatment with methiothepin (10  μg kg−1), WAY-100,635 (100 μg kg−1) or GR127935T (250 μg kg−1), but was not affected by cyanopindolol (100 μg kg−1).The selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT1B/1D receptor agonists sumatriptan and L-694,247 inhibited the pressor response, whereas the 5-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor symapthetic responses.The selective 5-HT1A receptor antagonist WAY-100,635 (100 μg kg−1) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT1B/1D receptor antagonist GR127935T (250 μg kg−1) abolished the inhibition induced either by L-694,247 or sumatriptan.None of the 5-HT receptor agonists used in our experiments modified the pressor responses induced by exogenous noradrenaline (NA).These results suggest that the presynaptic inhibitory action of 5-CT on the electrically-induced pressor response is mediated by both r-5-HT1D and 5-HT1A receptors. PMID:9559906

  10. Subclassification of muscarinic receptors in the heart, urinary bladder and sympathetic ganglia in the pithed rat. Selectivity of some classical agonists.

    PubMed

    van Charldorp, K J; de Jonge, A; Thoolen, M J; van Zwieten, P A

    1985-12-01

    In pithed normotensive rats muscarinic receptors were characterized in heart, urinary bladder and sympathetic ganglia; the selectivity of some classical muscarinic agents for these subtypes was investigated. The potencies in decreasing heart rate, increasing bladder pressure and increasing diastolic blood pressure were measured for the following, intraarterially administered cholinergic agonists: McN-A-343 ([4-m-chlorophenylcarbamoyloxy]-2-butynyltrimethylammonium), pilocarpine, carbachol, oxotremorine, arecoline, acetyl-beta-methylcholine and acetylcholine. The selective M1-antagonist pirenzepine, the mixed M1/M2-antagonist dexetimide and the cardioselective M2-antagonist gallamine were used as tools for identification of the receptors. All data were obtained after intravenous pretreatment with a high dose of atenolol to eliminate tachycardia induced by stimulating sympathetic ganglionic muscarinic receptors. Dexetimide strongly antagonized the bradycardia as well as the increase in bladder pressure induced by pilocarpine, carbachol, oxotremorine, arecoline, acetyl-beta-methylcholine and acetylcholine, whereas pirenzepine was much less effective. Gallamine antagonized the bradycardia, whereas no influence was found on the bladder contraction. Pilocarpine acted as a partial agonist in reducing heart rate as well as in increasing bladder pressure, whereas McN-A-343 was almost ineffective in doses up to 1 mg/kg. The hypertensive response to pilocarpine and carbachol was less pronounced than that produced by McN-A-343. Pirenzepine and dexetimide significantly antagonized the hypertensive response to McN-A-343 and pilocarpine, whereas gallamine was much less effective. The hypertensive response induced by carbachol was totally blocked by hexamethonium. The other agonists used in this study did not produce a significant increase in diastolic blood pressure in doses that produced a maximal effect on heart rate and urinary bladder pressure.(ABSTRACT TRUNCATED AT 250 WORDS

  11. Systemic Anti-inflammatory Corticosteroid Reduces Mechanical Pain Behavior, Sympathetic Sprouting, and Elevation of Pro-inflammatory Cytokines in a Rat Model of Neuropathic Pain

    PubMed Central

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

    2007-01-01

    Background: Chronic pain models are commonly defined as either nerve-injury or inflammation models, but recent work suggests inflammatory processes are important in nerve injury-induced pain. Methods: In the rat spinal nerve ligation model, the authors examined effects of systemic corticosteroid triamcinolone acetonide (TA) on the cytokine protein profile and sympathetic sprouting in the axotomized sensory ganglia, excitability of sensory neurons, and mechanical sensitivity. Results: By postoperative day 3, marked increases (5- to 16-fold) in monocyte chemoattractant protein-1, growth-related oncogene (GRO/KC or CXCL1), and interleukin (IL)-6 were observed, whereas IL-4 and IL-2 levels fell more than 4-fold. The increased cytokines and number of sympathetic basket formations in the sensory ganglia were reduced toward normal values by TA given starting at the time of injury. IL-4 and IL-2 levels were not restored by TA. Systemic TA also reduced the firing rate and incidence of bursting activity, but not the overall incidence of spontaneous activity, in large- and medium-sized neurons. Mechanical hypersensitivity on postoperative day 3 was reduced by TA, and some effect could still be observed 4 days after cessation of TA. However, starting TA at day 7 was ineffective. Conclusions: Several components of the spinal nerve injury model are responsive to corticosteroid, suggesting inflammatory processes are important in the development of neuropathic pain. The observation that TA was effective when given starting at the time of injury suggests that steroid treatment might alter the development of chronic pain after surgical procedures that involve nerve injury, such as amputation or hernia repair. PMID:17721250

  12. Changes in the daily rhythm of serum testosterone levels following superior cervical sympathetic ganglionectomy in the cold-exposed rat: the role of the pineal.

    PubMed

    Peschke, E; Peschke, D; Peil, J; Rúzsás, C; Mess, B

    1988-01-01

    The effect superior cervical sympathetic ganglionectomy (Gx) exerted on the daily rhythm of serum testosterone levels was investigated in cold-exposed rats. Rhythmic changes in pineal and pituitary weights were also measured. 1. Exposure to cold (10 degrees C for 72 h) resulted in a significant decrease of serum testosterone level and in an increase of the pineal weight. 2. In neutral ambient temperature (24 degrees C) Gx, 30 d after operation, led to a moderate, statistically insignificant increase of serum testosterone levels and to decreased pineal weights (statistically significant). 3. The reactions provoked by cold exposure were counteracted by Gx. Testosterone levels, as well as the pineal weight, showed no remarkable change in the Gx, cold-exposed animals. 4. These results confirm our assumption that experimental manipulations of the pineal gland can provoke significant changes in the neuroendocrine system only under special loading circumstances, e.g., cold exposure. Sympathetic denervation of the pineal gland counteracts the cold-induced decrease of testosterone levels by counteracting the pineal antigonadotropic activity. 5. The empirical regression curves of the investigated parameters indicate that Gx or cold exposure provide a shift in the upper and lower limits of the daily rhythm. Partly inverted rhythms were also observed. 6. The presented results are discussed in relation to the parallel changes previously described in serum thyroxin, cholesterol, thyrotropin (TSH), and pituitary TSH levels. Thyroidal-gonadal interactions, as well as cold exposure as a stress-generating factor, have been considered in the possible explanation of the data herein reported. PMID:3367268

  13. Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat.

    PubMed

    Shimizu, Takahiro; Tanaka, Kenjiro; Nakamura, Kumiko; Taniuchi, Keisuke; Yawata, Toshio; Higashi, Youichirou; Ueba, Tetsuya; Dimitriadis, Fotios; Shimizu, Shogo; Yokotani, Kunihiko; Saito, Motoaki

    2014-07-01

    We recently reported that intracerebroventricularly administered 2-arachidonoylglycerol elevated plasma noradrenaline and adrenaline by brain monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms in the rat. These results suggest that 2-arachidonoylglycerol is hydrolyzed by MGL to free arachidonic acid, which is further metabolized to prostaglandins (PGs) by cyclooxygenase in the brain, thereby elevating plasma noradrenaline and adrenaline. On the other hand, 2-arachidonoylglycerol can be also metabolized by cyclooxygenase to PG glycerol esters (PG-Gs), which seems to be hydrolyzed by MGL to free PGs. Here, we examined the involvement of brain PG-Gs in the elevation of plasma noradrenaline and adrenaline regarding PGE2-G and prostanoid EP receptors using anesthetized male Wistar rats. Intracerebroventricularly administered PGE2-G (1.5 and 3 nmol/animal) dose-dependently elevated plasma noradrenaline but not adrenaline. PGE2-G also elevated systolic, mean and diastolic blood pressure and heart rate. The PGE2-G-induced elevation of plasma noradrenaline was attenuated by JZL184 (MGL inhibitor). Intracerebroventricularly administered PGE2 (0.3 and 1.5 nmol/animal) and sulprostone (0.1 and 0.3 nmol/animal) (EP1/EP3 agonist) also elevated plasma noradrenaline but not adrenaline in a dose-dependent manner. The sulprostone-induced elevation was attenuated by L-798,106 (EP3 antagonist), but not by SC-51322 (EP1 antagonist). L-798,106 also attenuated the PGE2-G- and PGE2-induced elevation of plasma noradrenaline, while PF-04418948 (EP2 antagonist) and L-161,982 (EP4 antagonist) had no effect on the PGE2-G-induced response. These results suggest a possibility that brain PGE2-G produced from 2-arachidonoylglycerol can be hydrolyzed to free PGE2, thereby activating central sympathetic outflow by brain prostanoid EP3 receptor-mediated mechanisms in the rat. PMID:24657150

  14. Blocking Sympathetic Nervous System Reverses Partially Stroke-Induced Immunosuppression but does not Aggravate Functional Outcome After Experimental Stroke in Rats.

    PubMed

    Deng, Qi-Wen; Yang, Heng; Yan, Fu-Ling; Wang, Huan; Xing, Fang-Lan; Zuo, Lei; Zhang, Han-Qing

    2016-08-01

    Stoke results in activation of the sympathetic nervous system (SNS), inducing systemic immunosuppression. However, the potential mechanisms underlying stroke-induced immunosuppression remain unclear. Here, we determined the SNS effects on functional outcome and explored the interactions among SNS, β-arrestin2 and nuclear factor-κB (NF-κB) after experimental stroke in rats. In the current study, stroke was induced by a transient middle cerebral artery occlusion (MCAO) in rats, and SNS activity was inhibited by intraperitoneal injection of 6-hydroxydopamine HBr (6-OHDA). 7.0 T Micro-MRI and Longa score were employed to assess the functional outcome after stroke. Flow cytometry and ELISA assay were used to measure the expression of MHC class II, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Western blot was conducted to analyze β-arrestin2 and NF-κB protein expression levels after experimental stroke. We found significantly increased infarct volumes and functional impairment after MCAO at different post-surgery time points, which were not aggravated by 6-OHDA treatment. SNS blockade partially reversed the expression of MHC class II after stroke over time, as well as TNF-α and IFN-γ levels in lipopolysaccharide-stimulated macrophages in vitro. Treatment of MCAO rats with SNS-inhibitor significantly diminished NF-κB activation and enhanced β-arrestin2 expression after stroke. This study suggests that pharmacological SNS inhibition dose not aggravate functional outcome after stroke. Stroke-induced immunosuppression may be involved in the SNS-β-arrestin2-NF-κB pathway. PMID:27059792

  15. Specific role of α2A - and α2B -, but not α2C -, adrenoceptor subtypes in the inhibition of the vasopressor sympathetic out-flow in diabetic pithed rats.

    PubMed

    Altamirano-Espinoza, Alain H; Manrique-Maldonado, Guadalupe; Marichal-Cancino, Bruno A; Villalón, Carlos M

    2015-07-01

    Several lines of evidence have shown an association of diabetes with a catecholamines' aberrant homeostasis involving a drastic change in the expression of adrenoceptors. This homeostatic alteration includes, among other things, atypical actions of α2 -adrenoceptor agonists within central and peripheral α2 -adrenoceptors (e.g. profound antinociceptive effects in diabetic subjects). Hence, this study investigated the pharmacological profile of the α2 -adrenoceptor subtypes that inhibit the vasopressor sympathetic out-flow in streptozotocin-pre-treated (diabetic) pithed rats. For this purpose, B-HT 933 (up to 30 μg/kg min) was used as a selective α2 -adrenoceptor agonist and rauwolscine as a non-selective α2A/2B/2C -adrenoceptor antagonist; in addition, BRL 44408, imiloxan and JP-1302 were used as subtype-selective α2A -, α2B - and α2C -adrenoceptor antagonists, respectively (all given i.v.). I.v. continuous infusions of B-HT 933 inhibited the vasopressor responses induced by electrical sympathetic stimulation without affecting those by i.v. bolus injections of noradrenaline in both normoglycaemic and diabetic rats. Interestingly, the ED50 for B-HT 933 in diabetic rats (25 μg/kg min) was almost 1-log unit greater than that in normoglycaemic rats (3 μg/kg.min). Moreover, the sympatho-inhibition induced by 10 μg/kg min B-HT 933 in diabetic rats was (i) abolished by 300 μg/kg rauwolscine or 100 and 300 μg/kg BRL 44408; (ii) partially blocked by 1000 μg/kg imiloxan; and (iii) unchanged by 1000 μg/kg JP-1302. Our findings, taken together, suggest that B-HT 933 has a less potent inhibitory effect on the sympathetic vasopressor responses in diabetic (compared to normoglycaemic) rats and that can probably be ascribed to a down-regulation of α2C -adrenoceptors. PMID:25407049

  16. Gβ₂ mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons.

    PubMed

    Hernández-Castellanos, Juan M; Vivas, Oscar; Garduño, Julieta; De la Cruz, Lizbeth; Arenas, Isabel; Elías-Viñas, David; Mackie, Ken; García, David E

    2014-02-28

    Several neurotransmitters and hormones acting through G protein-coupled receptors elicit a voltage-dependent regulation of CaV2.2 channels, having profound effects on cell function and the organism. It has been hypothesized that protein-protein interactions define specificity in signal transduction. Yet it is unknown how the molecular interactions in an intracellular signaling cascade determine the specificity of the voltage-dependent regulation induced by a specific neurotransmitter. It has been suspected that specific effector regions on the Gβ subunits of the G proteins are responsible for voltage-dependent regulation. The present study examines whether a neurotransmitter's specificity can be revealed by simple ion-current kinetic analysis likely resulting from interactions between Gβ subunits and the channel-molecule. Noradrenaline is a neurotransmitter that induces voltage-dependent regulation. By using biochemical and patch-clamp methods in rat sympathetic neurons we examined calcium current modulation induced by each of the five Gβ subunits and found that Gβ2 mimics activation kinetic slowing of CaV2.2 channels by noradrenaline. Furthermore, overexpression of the Gβ2 isoform reproduces the effect of noradrenaline in the willing-reluctant model. These results advance our understanding on the mechanisms by which signals conveying from a variety of membrane receptors are able to display precise homeostatic responses. PMID:24513289

  17. 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

  18. Noradrenaline synthesis after sympathetic nerve activation in rat atria and its dependence on calcium but not CAM kinase II and protein kinases A or C.

    PubMed Central

    Kotsonis, P.; Binko, J.; Majewski, H.

    1996-01-01

    1. The biosynthesis of noradrenaline following sympathetic nerve activation was investigated in rat atria. In particular the time course of noradrenaline synthesis changes, the relationship of changes in synthesis to transmitter release and the possible roles of second messengers and protein kinases were examined. 2. Rat atria incubated with the precursor [3H]-tyrosine synthesized [3H]-noradrenaline. Synthesis was enhanced following pulsatile electrical field stimulation (3 Hz for 5 min) with the bulk of the increase occurring in the first 45 min after the commencement of electrical stimulation. In separate experiments rat atria were pre-incubated with [3H]-noradrenaline and the radioactive outflow in response to electrical field stimulation (3 Hz for 5 min) was taken as an index of noradrenaline release. 3. Stimulation-induced (S-I) noradrenaline synthesis was significantly correlated to S-I noradrenaline release for a variety of procedures which modulate noradrenaline release by mechanisms altering Ca2+ entry into the neurone (r2 = 0.99): those which decreased release: tetrodotoxin (0.3 microM), Ca(2+)-free medium, lowering the frequency of nerve activation to 1 Hz, and those which increased release, tetraethylammonium (0.3 mM), phentolamine (1 microM) and the combination of phentolamine (1 microM) and adenosine (10 microM). On the strength of this relationship we suggest that Ca2+ entry is a determining factor in S-I synthesis changes rather than the amount of noradrenaline released. Indeed the reduction in noradrenaline release with the calmodulin-dependent protein (CAM) kinase II inhibitor KN-62 (10 microM) which acts subsequent to Ca2+ entry, did not affect S-I synthesis. 4. The cell permeable cyclic AMP analogue, 8-bromoadenosine 3',5'-monophosphate (BrcAMP, 90 and 270 microM), dose-dependently increased basal [3H]-noradrenaline synthesis in unstimulated rat atria. This effect was antagonized by the selective protein kinase A (PKA) antagonist, Rp-8

  19. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

    EPA Science Inventory

    Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

  20. Further evidence for the role of histamine H3, but not H1, H2 or H4, receptors in immepip-induced inhibition of the rat cardioaccelerator sympathetic outflow.

    PubMed

    Pinacho-García, Manuel; Marichal-Cancino, Bruno A; Villalón, Carlos M

    2016-02-15

    Since histamine H3 and H4 receptors are coupled to heterotrimeric Gi/o proteins, a signal transduction pathway associated with inhibition of neurotransmitter release, the present study has investigated the inhibition of the rat cardioaccelerator sympathetic outflow induced by the H3/H4 receptor agonist immepip by using antagonists for histamine H1 (ketotifen), H2 (ranitidine), H3 (thioperamide) and H4 (JNJ7777120) receptors. For this purpose, 102 male Wistar rats were pithed, artificially ventilated and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n=90) or i.v. bolus injections of noradrenaline (n=12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively. I.v. continuous infusions of immepip (3 and 10 μg/kg min), but not of saline (0.02 ml/min), dose-dependently inhibited the sympathetically-induced tachycardic responses. Moreover, the cardiac sympatho-inhibition induced by 10 μg/kg min immepip (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unaltered after i.v. treatment with 1 ml/kg vehicle, 100 μg/kg ketotifen, 3000 μg/kg ranitidine, 30 μg/kg thioperamide or 300 μg/kg JNJ7777120; and (ii) abolished after 100 μg/kg thioperamide (i.v.). These doses of antagonists, which did not affect per se the sympathetically-induced tachycardic responses, were high enough to block their respective receptors. In conclusion, the cardiac sympatho-inhibition induced by 10 μg/kg.min immepip involves histamine H3 receptors, with further pharmacological evidence excluding the involvement of H1, H2 and H4 receptors. PMID:26826593

  1. The storage of endogenous noradrenaline in sympathetic nerve terminals

    PubMed Central

    Bisby, M. A.; Fillenz, Marianne

    1971-01-01

    1. The subcellular distribution of noradrenaline in sympathetic nerve terminals of rat vas deferens and cat spleen has been studied by cell fractionation methods combined with fluorescence and electronmicroscopic histochemical methods for noradrenaline. 2. Pinched-off axon varicosities (synaptosomes) were isolated and identified by fluorescence and electronmicroscopy in the mitochondrial pellet. 3. The proportion of large to small dense-cored vesicles in electronmicrographs of sympathetic nerve terminals varies in different organs. In rat vas deferens 4% and in cat spleen 20% are large vesicles. 4. Density gradients of rat vas deferens have a single low density peak of noradrenaline at 0·6 M sucrose, whereas those of cat spleen have an additional peak of noradrenaline at 1·1 M sucrose. 5. Small dense-cored vesicles were identified electronmicroscopically in the low density fractions and large dense-cored vesicles in the high density fractions from density gradients. 6. We conclude that both small and large dense-cored vesicles store noradrenaline. ImagesPlate 1Plate 2Plate 3 PMID:5579649

  2. Fluorophore-assisted light inactivation produces both targeted and collateral effects on N-type calcium channel modulation in rat sympathetic neurons

    PubMed Central

    Guo, Juan; Chen, Huanmian; Puhl, Henry L; Ikeda*, Stephen R

    2006-01-01

    Fluorophore-assisted light inactivation (FALI) is a method to inactivate specific proteins on a time scale of seconds to minutes using either diffuse or coherent light. Here we examine a novel FALI modality that utilizes a fluorescein-conjugated polypeptide, α-bungarotoxin (BTX) and a 13 amino acid BTX-binding site engineered into the N-terminus of metabotropic glutamate receptor 8a (mGluR8a), a class C G-protein-coupled receptor (GPCR). The tagged mGluR8a was expressed in rat sympathetic neurons and labelled with fluorescein-conjugated BTX (FL-BTX). The efficacy of FALI was evaluated by monitoring mGluR8a-mediated inhibition of calcium currents (ICa) using whole-cell voltage-clamp techniques. Following either wide-field or laser illumination of FL-BTX-labelled neurons, mGluR8a-mediated ICa inhibition was greatly attenuated whereas holding current and basal ICa, measures of non-specific effects, were minimally affected. Sodium azide, a collision quencher of singlet oxygen, reduced the magnitude of FALI-mediated effects supporting a role for reactive oxygen species in the process. Although these results were consistent with an acute inactivation of mGluR8a, the intended target, two findings confounded this interpretation. First, effects on a natively expressed signalling pathway, α2-adrenergic receptor-mediated ICa modulation, were observed following illumination of neurons expressing FL-BTX-labelled sodium channel β2 subunits or ionotropic 5-HT3 receptors, proteins with no overt relationship to GPCR signalling pathways. Second, GPCR-independent ICa modulation induced with intracellular guanylyl imidophosphate was also attenuated by FALI. These data challenge the assumption that the fluorophore-tagged protein is the sole target of FALI and provide evidence that collateral damage to proximal proteins occurs following fluorophore illumination. PMID:16873413

  3. Analysis of anandamide- and lysophosphatidylinositol-induced inhibition of the vasopressor responses produced by sympathetic stimulation or noradrenaline in pithed rats.

    PubMed

    Marichal-Cancino, Bruno A; Manrique-Maldonado, Guadalupe; Altamirano-Espinoza, Alain H; Ruiz-Salinas, Inna; González-Hernández, Abimael; Maassenvandenbrink, Antoinette; Villalón, Carlos M

    2013-12-01

    The endocannabinoid system exhibits multiple functions in cardiovascular regulation mainly by cannabinoid (CB1 and CB2) receptors, vanilloid TRPV1 receptors and, probably, by the orphan G protein-coupled receptor 55 (GPR55). Hence, the role of these receptors was investigated in Wistar pithed rats on anandamide- and lysophosphatidylinositol (LPI)-induced inhibition of the vasopressor responses induced by preganglionic (T7-T9) stimulation of the vasopressor sympathetic outflow or i.v. bolus injections of noradrenaline. The corresponding frequency- and dose-dependent vasopressor responses were analyzed before and during i.v. continuous infusions of anandamide (CB1, CB2, TRPV1 and GPR55), JWH-015 (CB2) and LPI (GPR55) in animals receiving (i.v.) the antagonists NIDA41020 (CB1), AM630 (CB2), capsazepine (TRPV1) and/or cannabidiol (GPR55). Anandamide (0.1-3.1 μg/kg min) inhibited the vasopressor responses by electrical stimulation, but not those by noradrenaline; while LPI (5.6-10 μg/kg min) inhibited both responses. In contrast, JWH-015 (5.6-10 μg/kg min) failed to induce sympatho-inhibition. Anandamide-induced sympatho-inhibition was: (i) dose-dependently blocked by 31 and 100 μg/kg NIDA41020; (ii) slightly blocked by 310 μg/kg AM630 or 31 μg/kg cannabidiol; and (iii) unaffected by 310 μg/kg capsazepine. Moreover, LPI-induced inhibition of both vasopressor responses was blocked and abolished by 10 and 31 μg/kg cannabidiol, respectively, and weakly blocked by 100 μg/kg NIDA41020. Thus, the sympatho-inhibition by anandamide is primarily mediated by cannabinoid CB1 and, minimally, by cannabidiol-sensitive receptors. In contrast, LPI-induced inhibition of both responses seems to be mainly mediated by postjunctional cannabidiol-sensitive (presumably endothelial GPR55) receptors. PMID:24076186

  4. Regeneration of putative sensory and sympathetic cutaneous nerve endings in the rat foot after sciatic nerve injury.

    PubMed

    Stankovic, N; Johansson, O; Hildebrand, C

    1996-01-01

    The present study examines the occurrence of calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin from normal and nerve-injured rats. After neurotomy/suture, glabrous skin samples contain few calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profies. The number of calcitonin gene-related peptide- and substance P-like immunoreacive profiles in the epidermis is significantly subnormal. Hairy skin from these rats does also contain few calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profiles. In addition, the presence of epidermal calcitonin gene-related peptide-like imunoreactive profiles in glabrous skin is subnormal on the contralateral side. After nerve crush injury, the occurrence of calcitonin gene-related peptide-like, but not substance P-like, immunoreactive profiles in th epidermis of the glabrous skin is significantly subnormal. The occurrence of tyrosine hylase-like immnunoreactive fibres in relation to the digital artery is also subnormal. The occurrence in hairy skin of calcitonin gene-related peptide-like immunoreactive, substance P-like immunoreactive and tyrosine hydroxylase-like immunoreactive profiles is subnormal. In both skin types, the contralateral occurrence of such profiles is subjectively normal. These results show that the occurrence of calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin is clearly subnormal after neurotomy and suture and less abnormal after nerve crush. After neurotomy and suture the contralateral side is also affected. PMID:10970110

  5. Decreased endothelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats.

    PubMed

    da Cunha, Natalia Veronez; Pinge-Filho, Phileno; Panis, Carolina; Silva, Bruno Rodrigues; Pernomian, Laena; Grando, Marcella Daruge; Cecchini, Rubens; Bendhack, Lusiane Maria; Martins-Pinge, Marli Cardoso

    2014-05-15

    We investigated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) on autonomic cardiovascular parameters, vascular reactivity, and endothelial cells isolated from aorta of monosodium glutamate (MSG) obese rats. Obesity was induced by administration of 4 mg/g body wt of MSG or equimolar saline [control (CTR)] to newborn rats. At the 60th day, the treatment was started with N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) or 0.9% saline. At the 90th day, after artery catheterization, mean arterial pressure (MAP) and heart rate were recorded. Plasma was collected to assess lipid peroxidation. Endothelial cells isolated from aorta were evaluated by flow cytometry and fluorescence intensity (FI) emitted by NO-sensitive dye [4,5-diaminofluoresceindiacetate (DAF-2DA)] and by ROS-sensitive dye [dihydroethidium (DHE)]. Vascular reactivity was made by concentration-response curves of acetylcholine. MSG showed hypertension compared with CTR. Treatment with L-NAME increased MAP only in CTR. The MSG induced an increase in the low-frequency (LF) band and a decrease in the high-frequency band of pulse interval. L-NAME treatment increased the LF band of systolic arterial pressure only in CTR without changes in MSG. Lipid peroxidation levels were higher in MSG and were attenuated after L-NAME. In endothelial cells, basal FI to DAF was higher in CTR than in MSG. In both groups, acetylcholine increased FI for DAF from basal. The FI baseline to DHE was higher in MSG than in CTR. Acetylcholine increased FI to DHE in the CTR group, but decreased in MSG animals. We suggest that reduced NO production and increased production of ROS may contribute to hypertension in obese MSG animals. PMID:24633548

  6. 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.

  7. Prognostic Significance of Imaging Myocardial Sympathetic Innervation.

    PubMed

    Malhotra, Saurabh; Fernandez, Stanley F; Fallavollita, James A; Canty, John M

    2015-08-01

    There has been a longstanding interest in understanding whether the presence of inhomogeneity in myocardial sympathetic innervation can predict patients at risk of sudden cardiac arrest from lethal ventricular arrhythmias. The advent of radiolabeled norepinephrine analogs has allowed this to be imaged in patients with ischemic and non-ischemic cardiomyopathy using single, photon emission computed tomography (SPECT) and positron emission tomography (PET). Several observational studies have demonstrated that globally elevated myocardial sympathetic tone (as reflected by reduced myocardial norepinephrine analog uptake) can predict composite cardiac end-points including total cardiovascular mortality. More recent studies have indicated that quantifying the extent of regional denervation can predict the risk of lethal ventricular arrhythmias and sudden cardiac death. This review will summarize our current understanding of the prognostic significance of altered myocardial sympathetic innervation. PMID:26087899

  8. 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

  9. 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

  10. The 5-HT1-like receptors mediating inhibition of sympathetic vasopressor outflow in the pithed rat: operational correlation with the 5-HT1A, 5-HT1B and 5-HT1D subtypes

    PubMed Central

    Villalón, Carlos M; Centurión, David; Rabelo, Gonzalo; de Vries, Peter; Saxena, Pramod R; Sánchez-López, Araceli

    1998-01-01

    It has been suggested that the inhibition of sympathetically-induced vasopressor responses produced by 5-hydroxytryptamine (5-HT) in pithed rats is mediated by 5-HT1-like receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors.Intravenous (i.v.) continuous infusions of 5-HT and the 5-HT1 receptor agonists, 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP 93,129 (5-HT1B) and sumatriptan (5-HT1B/1D), resulted in a dose-dependent inhibition of sympathetically-induced vasopressor responses.The sympatho-inhibitory responses induced by 5-HT, 8-OH-DPAT, indorenate, CP 93,129 or sumatriptan were analysed before and after i.v. treatment with blocking doses of the putative 5-HT receptor antagonists, WAY 100635 (5-HT1A), cyanopindolol (5-HT1A/1B) or GR 127935 (5-HT1B/1D). Thus, after WAY 100635, the responses to 5-HT and indorenate, but not to 8-OH-DPAT, CP 93,129 and sumatriptan, were blocked. After cyanopindolol, the responses to 5-HT, indorenate and CP 93,129 were abolished, whilst those to 8-OH-DPAT and sumatriptan (except at the lowest frequency of stimulation) remained unaltered. In contrast, after GR 127935, the responses to 5-HT, CP 93,129 and sumatriptan, but not to 8-OH-DPAT and indorenate, were abolished.In additional experiments, the inhibition induced by 5-HT was not modified after 5-HT7 receptor blocking doses of mesulergine.The above results suggest that the 5-HT1-like receptors, which inhibit the sympathetic vasopressor outflow in pithed rats, display the pharmacological profile of the 5-HT1A, 5-HT1B and 5-HT1D, but not that of 5-HT7, receptors. PMID:9692787

  11. Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration: a whole cell recording study in situ

    PubMed Central

    Stalbovskiy, Alexey O; Briant, Linford J B; Paton, Julian F R; Pickering, Anthony E

    2014-01-01

    Sympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing from the CNS to the periphery to reach the target organs. Although previous in vivo and in vitro cell recording studies have explored their electrophysiological characteristics, it has not been possible to relate these characteristics to their roles in cardiorespiratory reflex integration. We used the working heart–brainstem preparation to make whole cell patch clamp recordings from T3–4 SPNs (n = 98). These SPNs were classified by their distinct responses to activation of the peripheral chemoreflex, diving response and arterial baroreflex, allowing the discrimination of muscle vasoconstrictor-like (MVClike, 39%) from cutaneous vasoconstrictor-like (CVClike, 28%) SPNs. The MVClike SPNs have higher baseline firing frequencies (2.52 ± 0.33 Hz vs. CVClike 1.34 ± 0.17 Hz, P = 0.007). The CVClike have longer after-hyperpolarisations (314 ± 36 ms vs. MVClike 191 ± 13 ms, P < 0.001) and lower input resistance (346 ± 49  MΩ vs. MVClike 496 ± 41 MΩ, P < 0.05). MVClike firing was respiratory-modulated with peak discharge in the late inspiratory/early expiratory phase and this activity was generated by both a tonic and respiratory-modulated barrage of synaptic events that were blocked by intrathecal kynurenate. In contrast, the activity of CVClike SPNs was underpinned by rhythmical membrane potential oscillations suggestive of gap junctional coupling. Thus, we have related the intrinsic electrophysiological properties of two classes of SPNs in situ to their roles in cardiorespiratory reflex integration and have shown that they deploy different cellular mechanisms that are likely to influence how they integrate and shape the distinctive sympathetic outputs. PMID:24665100

  12. Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration: a whole cell recording study in situ.

    PubMed

    Stalbovskiy, Alexey O; Briant, Linford J B; Paton, Julian F R; Pickering, Anthony E

    2014-05-15

    Sympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing from the CNS to the periphery to reach the target organs. Although previous in vivo and in vitro cell recording studies have explored their electrophysiological characteristics, it has not been possible to relate these characteristics to their roles in cardiorespiratory reflex integration. We used the working heart-brainstem preparation to make whole cell patch clamp recordings from T3-4 SPNs (n = 98). These SPNs were classified by their distinct responses to activation of the peripheral chemoreflex, diving response and arterial baroreflex, allowing the discrimination of muscle vasoconstrictor-like (MVC(like), 39%) from cutaneous vasoconstrictor-like (CVC(like), 28%) SPNs. The MVC(like) SPNs have higher baseline firing frequencies (2.52 ± 0.33 Hz vs. CVC(like) 1.34 ± 0.17 Hz, P = 0.007). The CVC(like) have longer after-hyperpolarisations (314 ± 36 ms vs. MVC(like) 191 ± 13 ms, P < 0.001) and lower input resistance (346 ± 49 MΩ vs. MVC(like) 496 ± 41 MΩ, P < 0.05). MVC(like) firing was respiratory-modulated with peak discharge in the late inspiratory/early expiratory phase and this activity was generated by both a tonic and respiratory-modulated barrage of synaptic events that were blocked by intrathecal kynurenate. In contrast, the activity of CVC(like) SPNs was underpinned by rhythmical membrane potential oscillations suggestive of gap junctional coupling. Thus, we have related the intrinsic electrophysiological properties of two classes of SPNs in situ to their roles in cardiorespiratory reflex integration and have shown that they deploy different cellular mechanisms that are likely to influence how they integrate and shape the distinctive sympathetic outputs. PMID:24665100

  13. 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

  14. [Rat uterus anastomoses in a single and a double layer].

    PubMed

    Gianaroli, L; Bufferli, M; Livani, M F

    1980-11-15

    The Authors display their results on microsurgical operations in rat's uteri. After having described the instruments and methods used, the surgical techniques and the differences between a single and a double layer suture are discussed. However the formation of intraoperative adherences, which can damage the functional results of the intervention, is studied. And what's more the mean number of live born foetuses is seen as an attainable parameter for future validations. PMID:7011341

  15. Continuous Thoracic Sympathetic Ganglion Block in Complex Regional Pain Syndrome Patients with Spinal Cord Stimulation Implantation

    PubMed Central

    Kim, EungDon; Roh, MiSun; Kim, SooHyang; Jo, DaeHyun

    2016-01-01

    The sympathetic block is widely used for treating neuropathic pain such as complex regional pain syndrome (CRPS). However, single sympathetic block often provides only short-term effect. Moreover, frequent procedures for sympathetic block may increase the risk of complications. The use of epidural route may be limited by concern of infection in case of previous implantation of the spinal cord stimulation (SCS). In contrast, a continuous sympathetic block can be administered without such concerns. The continuous thoracic sympathetic block (TSGB) has been used to treat the ischemic disease and other neuropathic conditions such as postherpetic neuralgia. We administered continuous thoracic sympathetic block using catheter in CRPS patients who underwent SCS implantations and achieved desirable outcomes. We believe a continuous sympathetic block is a considerable option before performing neurolysis or radiofrequency rhizotomy and even after SCS implantation.

  16. Catecholamine-induced excitation of nociceptors in sympathetically maintained pain.

    PubMed

    Jørum, Ellen; Ørstavik, Kristin; Schmidt, Roland; Namer, Barbara; Carr, Richard W; Kvarstein, Gunnvald; Hilliges, Marita; Handwerker, Hermann; Torebjörk, Erik; Schmelz, Martin

    2007-02-01

    Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found. PMID:16997471

  17. Single Glucose Biofuel Cells Implanted in Rats Power Electronic Devices

    PubMed Central

    Zebda, A.; Cosnier, S.; Alcaraz, J.-P.; Holzinger, M.; Le Goff, A.; Gondran, C.; Boucher, F.; Giroud, F.; Gorgy, K.; Lamraoui, H.; Cinquin, P.

    2013-01-01

    We describe the first implanted glucose biofuel cell (GBFC) that is capable of generating sufficient power from a mammal's body fluids to act as the sole power source for electronic devices. This GBFC is based on carbon nanotube/enzyme electrodes, which utilize glucose oxidase for glucose oxidation and laccase for dioxygen reduction. The GBFC, implanted in the abdominal cavity of a rat, produces an average open-circuit voltage of 0.57 V. This implanted GBFC delivered a power output of 38.7 μW, which corresponded to a power density of 193.5 μW cm−2 and a volumetric power of 161 μW mL−1. We demonstrate that one single implanted enzymatic GBFC can power a light-emitting diode (LED), or a digital thermometer. In addition, no signs of rejection or inflammation were observed after 110 days implantation in the rat. PMID:23519113

  18. Single glucose biofuel cells implanted in rats power electronic devices.

    PubMed

    Zebda, A; Cosnier, S; Alcaraz, J-P; Holzinger, M; Le Goff, A; Gondran, C; Boucher, F; Giroud, F; Gorgy, K; Lamraoui, H; Cinquin, P

    2013-01-01

    We describe the first implanted glucose biofuel cell (GBFC) that is capable of generating sufficient power from a mammal's body fluids to act as the sole power source for electronic devices. This GBFC is based on carbon nanotube/enzyme electrodes, which utilize glucose oxidase for glucose oxidation and laccase for dioxygen reduction. The GBFC, implanted in the abdominal cavity of a rat, produces an average open-circuit voltage of 0.57 V. This implanted GBFC delivered a power output of 38.7 μW, which corresponded to a power density of 193.5 μW cm(-2) and a volumetric power of 161 μW mL(-1). We demonstrate that one single implanted enzymatic GBFC can power a light-emitting diode (LED), or a digital thermometer. In addition, no signs of rejection or inflammation were observed after 110 days implantation in the rat. PMID:23519113

  19. Intraglomerular microcirculation: measurements of single glomerular loop flow in rats.

    PubMed

    Steinhausen, M; Zimmerhackl, B; Thederan, H; Dussel, R; Parekh, N; Esslinger, H U; von Hagens, G; Komitowski, D; Dallenbach, F D

    1981-08-01

    With the use of a new fluorescent microscopic technique, we were able to measure the mean intracapillary velocities and pressures of single capillary loops of renal glomeruli of living rats. The technique involved photographing and recording the flow of fluorescent latex particles through the glomerular loops with a television monitor. In 25 rats the single glomerular loop flow velocity was 781 +/- (SD) 271 micrometers . sec-1. The mean diameter of the capillary loops measured 8.4 +/- 1.4 micrometers; their lengths were 72.3 +/- 37.5 micrometers. From the decrease in velocity of flow along the capillary loop, we were able to evaluate the filtration equivalent for the capillary surface. It was possible to measure intracapillary pressures of single glomerular loops continuously under microscopic control. High intracapillary pressures correlated with high intracapillary velocities. From the data we obtained, we were unable to calculate a filtration equilibrium at the ends of the observed capillary loops. For further correlations, we injected the glomeruli we had studied in the living state and examined them with the scanning electron microscope. PMID:7289407

  20. Modulation of silent and constitutively active nociceptin/orphanin FQ receptors by potent receptor antagonists and Na+ ions in rat sympathetic neurons.

    PubMed

    Mahmoud, Saifeldin; Margas, Wojciech; Trapella, Claudio; Caló, Girolamo; Ruiz-Velasco, Victor

    2010-05-01

    The pharmacology of G protein-coupled receptors can be influenced by factors such as constitutive receptor activation and Na(+) ions. In this study, we examined the coupling of natively and heterologously expressed nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors with voltage-dependent Ca(2+) channels after exposure to four high-affinity NOP receptor blockers [[Nphe(1)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-101), 1-[1-(cyclooctylmethyl)-1,2,3,6-tetrahydro-5-(hydroxymethyl)-4-pyridinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (Trap-101), 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl}pyrrolidine-2-carboxamide (compound 24), and N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide hydrochloride (JTC-801)] in sympathetic neurons. The enhanced tonic inhibition of Ca(2+) currents in the absence of agonists, indicative of constitutively active NOP receptors in transfected neurons, was abolished after pretreatment with pertussis toxin. In control neurons, the four antagonists did not exert any effects when applied alone but significantly blocked the N/OFQ-mediated Ca(2+) current inhibition. Exposure of transfected neurons to UFP-101 resulted in partial agonist effects. In contrast, Trap-101, compound 24, and JTC-801 exerted inverse agonism, as measured by the loss of tonic Ca(2+) current inhibition. In experiments designed to measure the N/OFQ concentration-response relationship under varying Na(+) concentrations, a leftward shift of IC(50) values was observed after Na(+) exposure. Although similar N/OFQ efficacies were measured with all solutions, a significant decrease of Hill coefficient values was obtained with increasing Na(+) concentrations. Examination of the allosteric effects of Na(+) on heterologously overexpressed NOP receptors showed that the tonic Ca(2+) current inhibition was abolished in the presence of the monovalent cation. These results demonstrate that constitutively active NOP receptors exhibit differential blocker

  1. Low-order chaos in sympathetic nerve activity causes 1/f fluctuation of heartbeat intervals

    NASA Astrophysics Data System (ADS)

    Osaka, Motohisa; Kumagai, Hiroo; Sakata, Katsufumi; Onami, Toshiko; Chon, Ki H.; Watanabe, Mari A.; Saruta, Takao

    2004-04-01

    The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate that the dynamics of this system of 3 variables is low-order chaos, and that sympathetic nerve activity leads to heartbeat interval and blood pressure changes. It is suggested that 1/f scaling of heartbeat intervals results from the low-order chaos of these variables and that impaired regulation of blood pressure by sympathetic nerve activity is likely to cause experimentally observable steeper scaling of heartbeat intervals in hypertensive (high blood pressure) rats.

  2. Low-order chaos in sympathetic nerve activity and scaling of heartbeat intervals

    NASA Astrophysics Data System (ADS)

    Osaka, Motohisa; Kumagai, Hiroo; Sakata, Katsufumi; Onami, Toshiko; Chon, Ki H.; Watanabe, Mari A.; Saruta, Takao

    2003-04-01

    The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate that the dynamics of this system of three variables is low-order chaos, and that sympathetic nerve activity leads to heartbeat interval and blood pressure changes. It is suggested that impaired regulation of blood pressure by sympathetic nerve activity is likely to cause experimentally observable steeper scaling of heartbeat intervals in hypertensive (high blood pressure) rats.

  3. Influence of a single gamma-irradiation on rat microflora.

    PubMed

    Benová, K; Falis, M; Toropila, M; Sehnalková, H; Pastvová, L

    2002-01-01

    Changes in leukocyte counts and in the gut microflora of laboratory rats irradiated with single whole-body dose of gamma rays (5.0 Gy) were determined. The number of leukocytes was lower especially 1 and 2 weeks after irradiation. A significant decrease in lymphocytes was observed 1 week and in monocytes 1 and 2 weeks after irradiation. In parallel with these changes, an increase in common microflora was observed; some microorganisms, which normally are not present in duodenum, liver and mouth cavity, were detected in these organs. PMID:12422530

  4. Influence of simulated microgravity on the sympathetic response to exercise

    NASA Technical Reports Server (NTRS)

    Woodman, C. R.; Kregel, K. C.; Tipton, C. M.

    1997-01-01

    Rats exposed to simulated conditions of microgravity exhibit reductions in aerobic exercise capacity that may be due to an impaired ability of the sympathetic nervous system (SNS) to mediate an increase in cardiac output and to redistribute blood flow. The purpose of this study was to quantify the sympathetic response to exercise in rats after exposure to 14 days of simulated microgravity or control conditions. To achieve this aim, rats were exposed to 14 days of head-down suspension (HDS) or cage control (CC) conditions. On day 14, norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of NE depletion after synthesis blockade was used to estimate SNS activity in the left ventricle, spleen, and soleus muscle during treadmill exercise at 75% of maximal oxygen uptake. When compared with CC rats, the sympathetic response to exercise in HDS rats was characterized by a lower rate of NE depletion in the left ventricle (-82%) and spleen (-42%). The rate of NE depletion in the soleus muscle was 47% higher. These differences could contribute to the decrement in aerobic capacity of HDS rats by impairing their ability to augment cardiac output and to redirect blood flow to actively contracting skeletal muscle during exercise.

  5. Single and Double Alternation Learning in Rats: The Role of Set Size and Correction

    ERIC Educational Resources Information Center

    Kundey, Shannon M. A.; Rowan, James D.

    2009-01-01

    In many experiments, rats have evidenced extreme difficulty mastering alternation patterns. In three experiments, we explored rats' ability to learn double alternation patterns and possible reasons behind their past difficulties with such patterns. In Experiment 1, rats learned single and double alternation patterns. In the second and third…

  6. Hypercapnia selectively attenuates the somato-sympathetic reflex.

    PubMed

    Makeham, John M; Goodchild, A K; Costin, N S; Pilowsky, Paul M

    2004-05-20

    The effects of hyperoxic hypercapnia (5, 10 or 15% CO2 in O2) on splanchnic sympathetic nerve activity (sSNA) and sympathetic reflexes such as the somato-sympathetic reflex or baroreflex were studied in urethane anaesthetised, paralysed, artificially ventilated and vagotomized Sprague-Dawley rats. Hypercapnia caused a small increase in mean arterial blood pressure (MAP) in the 10% CO2 group and a fall in heart rate (HR) in all three groups. sSNA increased in all three groups. Phrenic frequency and amplitude increased during hypercapnia, with frequency adapting back towards baseline during the CO2 exposure. The somato-sympathetic reflex was attenuated in the 5% CO2 group and abolished in the 10 and 15% CO2 groups, whereas there was little effect on the sSNA baroreflex. Hypercapnia significantly affects phrenic nerve activity (PNA), sSNA and selectively inhibits the somato-sympathetic reflex with little effect on the sSNA baroreflex. PMID:15134661

  7. Effect of sympathetic denervation of the pineal gland on maternal co-ordination of the circadian rhythm of alpha-amylase in parotid gland from young rats.

    PubMed

    Bellavía, S L; Sanz, E G; Gallará, R V; Carpentieri, A; Vermouth, N T

    1993-12-01

    Twenty-five-day-old rats maintained in constant darkness since birth and born from mothers kept in the dark since the 14th day of pregnancy showed a circadian rhythm of alpha-amylase content in parotid glands, which may be explained by a mechanism of maternal co-ordination. Rats in the same conditions, except that their mothers had been submitted to bilateral excision of the superior cervical ganglia 30 days before mating, did not show diurnal variations of alpha-amylase activity in the parotid glands. When ganglionectomized mothers were treated with a daily dose of melatonin (1 mg/kg) from the 14th day of gestation up to the 10th day of lactation, their litters showed significant diurnal variations of amylase in the parotid glands, suggesting a role of the maternal pineal gland in the maternal-fetal and/or maternal-neonatal transfer of photoperiodic information. PMID:8141675

  8. [Reflex sympathetic dystrophy].

    PubMed

    Oliveira, Marta; Manuela, Manuela; Cantinho, Guilhermina

    2011-01-01

    Reflex Sympathetic Dystrophy is rare in pediatrics. It is a complex regional pain syndrome, of unknown etiology, usually post-traumatic, characterized by dysfunctions of the musculoskeletal, vascular and skin systems: severe persistent pain of a limb, sensory and vascular alterations, associated disability and psychosocial dysfunction. The diagnosis is based in high clinical suspection. In children and adolescents there are aspects that are different from the adult ones. Excessive tests may result in worsening of the clinical symptoms. Bone scintigraphy can help. Pain treatment is difficult, not specific. Physical therapies and relaxation technics give some relief. Depression must be treated. This syndrome includes fibromyalgia and complex regional pain syndrome type I. We present a clinical report of an adolescent girl, referred for pain, cold temperature, pallor and functional disability of an inferior limb, all signals disclosed by a minor trauma. She had been diagnosed depression the year before. The bone scintigraphy was a decisive test. The treatment with gabapentin, C vitamin, physiotherapy and pshycotherapy has been effective. PMID:22713207

  9. 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.

  10. Dexmedetomidine and Regulation of Splenic Sympathetic Nerve Discharge

    PubMed Central

    Kenney, MJ; Larsen, BT; McMurphy, RM; Mason, D; Fels, RJ

    2014-01-01

    Recent lines of inquiry indicate sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses. PMID:24656574

  11. Angiotensin II Stimulates Sympathetic Neurotransmission to Adipose Tissue.

    PubMed

    King, Victoria L; English, Victoria L; Bharadwaj, Kalyani; Cassis, Lisa A

    2013-08-01

    Angiotensin II (AngII) facilitates sympathetic neurotransmission by regulating norepinephrine (NE) synthesis, release and uptake. These effects of AngII contribute to cardiovascular control. Previous studies in our laboratory demonstrated that chronic AngII infusion decreased body weight of rats. We hypothesized that AngII facilitates sympathetic neurotransmission to adipose tissue and may thereby decrease body weight. The effect of chronic AngII infusion on the NE uptake transporter and NE turnover was examined in metabolic (interscapular brown adipose tissue, ISBAT; epididymal fat, EF) and cardiovascular tissues (left ventricle, LV; kidney) of rats. To examine the uptake transporter saturation isotherms were performed using [(3)H]nisoxetine (NIS). At doses that lowered body weight, AngII significantly increased ISBAT [(3)H]NIS binding density. To quantify NE turnover, alpha-methyl-para-tyrosine (AMPT) was injected in saline-infused, AngII-infused, or saline-infused rats that were pair-fed to food intake of AngII-infused rats. AngII significantly increased the rate of NE decline in all tissues compared to saline. The rate of NE decline in EF was increased to a similar extent by AngII and by pair-feeding. In rats administered AngII and propranolol, reductions in food and water intake and body weight were eliminated. These data support the hypothesis that AngII facilitates sympathetic neurotransmission to adipose tissue. Increased sympathetic neurotransmission to adipose tissue following AngII exposure is suggested to contribute to reductions in body weight. PMID:24224084

  12. 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

  13. Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

    PubMed

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2016-08-26

    Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. PMID:27320860

  14. 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

  15. Computational solution of spike overlapping using data-based subtraction algorithms to resolve synchronous sympathetic nerve discharge

    PubMed Central

    Su, Chun-Kuei; Chiang, Chia-Hsun; Lee, Chia-Ming; Fan, Yu-Pei; Ho, Chiu-Ming; Shyu, Liang-Yu

    2013-01-01

    Sympathetic nerves conveying central commands to regulate visceral functions often display activities in synchronous bursts. To understand how individual fibers fire synchronously, we establish “oligofiber recording techniques” to record “several” nerve fiber activities simultaneously, using in vitro splanchnic sympathetic nerve–thoracic spinal cord preparations of neonatal rats as experimental models. While distinct spike potentials were easily recorded from collagenase-dissociated sympathetic fibers, a problem arising from synchronous nerve discharges is a higher incidence of complex waveforms resulted from spike overlapping. Because commercial softwares do not provide an explicit solution for spike overlapping, a series of custom-made LabVIEW programs incorporated with MATLAB scripts was therefore written for spike sorting. Spikes were represented as data points after waveform feature extraction and automatically grouped by k-means clustering followed by principal component analysis (PCA) to verify their waveform homogeneity. For dissimilar waveforms with exceeding Hotelling's T2 distances from the cluster centroids, a unique data-based subtraction algorithm (SA) was used to determine if they were the complex waveforms resulted from superimposing a spike pattern close to the cluster centroid with the other signals that could be observed in original recordings. In comparisons with commercial software, higher accuracy was achieved by analyses using our algorithms for the synthetic data that contained synchronous spiking and complex waveforms. Moreover, both T2-selected and SA-retrieved spikes were combined as unit activities. Quantitative analyses were performed to evaluate if unit activities truly originated from single fibers. We conclude that applications of our programs can help to resolve synchronous sympathetic nerve discharges (SND). PMID:24198782

  16. Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal.

    PubMed

    Kreipke, R E; Birren, S J

    2015-12-01

    Sympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β-adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β-adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size. PMID:26420487

  17. 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

  18. 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

  19. Single and multiple congenic strains for hydrocephalus in the H-Tx rat

    PubMed Central

    Jones, Hazel C.; Chen, Gin-Fu; Yehia, Baligh R.; Carter, Barbara J.; Akins, Elizabeth J.; Wolpin, Logan C.

    2010-01-01

    The H-Tx rat has fetal-onset hydrocephalus with a complex mode of inheritance. Previously, quantitative trait locus mapping using a backcross with Fischer F344 rats demonstrated genetic loci significantly linked to hydrocephalus on Chromosomes 10, 11, and 17. Hydrocephalus was preferentially associated with heterozygous alleles on Chrs 10 and 11 and with homozygous alleles on Chr 17. This study aimed to determine the phenotypic contribution of each locus by constructing single and multiple congenic strains. Single congenic rats were constructed using Fischer F344 as the recipient strain and a marker-assisted protocol. The homozygous strains were maintained for eight generations and the brains examined for dilated ventricles indicative for hydrocephalus. No congenic rats had severe (overt) hydrocephalus. A few pups and a significant number of adults had mild disease. The incidence was significantly higher in the C10 and C17 congenic strains than in the nonhydrocephalic F344 strain. Breeding to F344 to make F.H-Tx C10 or C11 rats heterozygous for the hydrocephalus locus failed to produce progeny with severe disease. Both bicongenic and tricongenic rats of different genotype combinations were constructed by crossing congenic rats. None had severe disease but the frequency of mild hydrocephalus in adults was similar to congenic rats and significantly higher than in the F344 strain. Rats with severe hydrocephalus were recovered in low numbers when single congenic or bicongenic rats were crossed with the parental H-Tx strain. It is concluded that the genetic and epigenetic factors contributing to severe hydrocephalus in the H-Tx strain are more complex than originally anticipated. PMID:15965786

  20. Histopathological changes in rat liver after a single high dose of aluminium.

    PubMed

    Bogdanović, Milka; Janeva, Ana Begić; Bulat, Petar

    2008-06-01

    Aluminium (Al) exposure may affect the liver of experimental animals. This investigation aimed at evaluating morphological changes in rat liver after a single high dose of Al (as metallic powder suspension). A total of forty female Wistar rats were divided in one exposed and one control group, 20 rats each. The exposed rats received 0.5 mL of sterile physiological suspension of fine Al powder in the concentration of 100 mg mL-1 intraperitoneally (50 mg Al per rat). After 7 weeks all animals were killed (by exsanguination from the abdominal aorta in ether anaesthesia). Liver aluminium was analysed using electrothermal atomic absorption spectrometry. For light microscopy the liver tissue was stained with hematoxylin and eosin, and for histochemical analysis with aurin threecarbocsillic acid (aluminon). Liver Al level was markedly higher in the exposed (37.1 microg g-1) than in control rats (0.71 microg g-1). The exposed rats showed crystalloid Al inclusions in the capsular, subcapsular, and portal liver tissue. The basic liver structure remained intact. Slightly multiplied bile ductuli were found in 16 of 20 exposed and in 8 of 20 control rats. Three exposed rats had mycrovesicular steatosis. The peritoneum and Glisson's capsule showed strong macrophage infiltration and a foreign-body-like reaction with multiple giant macrophages containing Al crystalloid inclusions. Although this reaction was a defense against the metal, some Al passed this barrier and entered the liver tissue, exerting toxic effects in bile ductuli and hepatocytes. PMID:18573746

  1. Heart Rates of Male and Female Sprague–Dawley and Spontaneously Hypertensive Rats Housed Singly or in Groups

    PubMed Central

    Azar, Toni; Sharp, Jody; Lawson, David

    2011-01-01

    This study was conducted to confirm our previous reports that group housing lowered basal heart rate and various evoked heart-rate responses in Sprague–Dawley male and female rats and to extend these observations to spontaneously hypertensive rats. Heart rate data were collected by using radiotelemetry. Initially, group- and single-housed rats were evaluated in the same animal room at the same time. Under these conditions, group-housing did not decrease heart rate in undisturbed male and female rats of either strain compared with single-housed rats. Separate studies then were conducted to examine single-housed rats living in the room with only single-housed rats. When group-housed rats were compared with these single-housed rats, undisturbed heart rates were reduced significantly, confirming our previous reports for Sprague–Dawley rats. However, evoked heart rate responses to acute procedures were not reduced universally in group-housed rats compared with either condition of single housing. Responses to some procedures were reduced, but others were not affected or were significantly enhanced by group housing compared with one or both of the single-housing conditions. This difference may have been due, in part, to different sensory stimuli being evoked by the various procedures. In addition, the variables of sex and strain interacted with housing condition. Additional studies are needed to resolve the mechanisms by which evoked cardiovascular responses are affected by housing, sex, and strain. PMID:21439210

  2. Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias

    PubMed Central

    Hasan, Wohaib; Streiff, Cole T.; Houle, Jennifer C.; Woodward, William R.; Giraud, George D.; Brooks, Virginia L.; Habecker, Beth A.

    2013-01-01

    Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250–275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events. PMID:24014675

  3. Hindlimb unweighting does not alter vasoconstrictor responsiveness and nitric oxide-mediated inhibition of sympathetic vasoconstriction

    PubMed Central

    Just, Timothy P; Jendzjowsky, Nicholas G; DeLorey, Darren S

    2015-01-01

    Abstract We tested the hypothesis that physical inactivity would increase sympathetic vasoconstrictor responsiveness and diminish NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague–Dawley rats (n = 33) were randomly assigned to sedentary time control (S) or hindlimb unweighted (HU) groups for 21 days. Following the intervention, rats were anaesthetized and instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NO synthase blockade with l-NAME (5 mg kg i.v.). Sympathetic vasoconstrictor responsiveness was not different (P > 0.05) in S and HU rats at rest (S, 2 Hz, −26 ± 8% and 5 Hz, −46 ± 12%; and HU, 2 Hz, −29 ± 9% and 5 Hz, −51 ± 10%) and during contraction (S, 2 Hz, −10 ± 7% and 5 Hz, −23 ± 11%; and HU, 2 Hz, −9 ± 5% and 5 Hz, −22 ± 7%). Nitric oxide synthase blockade caused a similar increase (P > 0.05) in sympathetic vasoconstrictor responsiveness in HU and S rats at rest (S, 2 Hz, −41 ± 7% and 5 Hz, −58 ± 8%; and HU, 2 Hz, −43 ± 6% and 5 Hz, −63 ± 8%) and during muscle contraction (S, 2 Hz, −15 ± 6% and 5 Hz, −31 ± 11%; and HU, 2 Hz, −12 ± 5% and 5 Hz, −29 ± 8%). Skeletal muscle NO synthase expression and ACh-mediated vasodilatation were also not different between HU and S rats. These data suggest that HU does not alter sympathetic vasoconstrictor responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Key points Physical inactivity increases the risk of cardiovascular disease and may alter sympathetic nervous system control of vascular

  4. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats

    PubMed Central

    Sun, Seung-Ho; Park, Sunju; Jeong, Jong-Jin; Lee, Kwang-Ho; Yu, Jun-Sang; Seo, Hyung-Sik; Kwon, Ki-Rok

    2015-01-01

    Objectives: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg. PMID:26120487

  5. Bacillus anthracis lethal toxin alters regulation of visceral sympathetic nerve discharge.

    PubMed

    Garcia, A A; Fels, R J; Mosher, L J; Kenney, M J

    2012-03-01

    Bacillus anthracis infection is a pathophysiological condition that is complicated by progressive decreases in mean arterial pressure (MAP). Lethal toxin (LeTx) is central to the pathogenesis of B. anthracis infection, and the sympathetic nervous system plays a critical role in physiological regulation of acute stressors. However, the effect of LeTx on sympathetic nerve discharge (SND), a critical link between central sympathetic neural circuits and MAP regulation, remains unknown. We determined visceral (renal, splenic, and adrenal) SND responses to continuous infusion of LeTx [lethal factor (100 μg/kg) + protective antigen (200 μg/kg) infused at 0.5 ml/h for ≤6 h] and vehicle (infused at 0.5 ml/h) in anesthetized, baroreceptor-intact and baroreceptor (sinoaortic)-denervated (SAD) Sprague-Dawley rats. LeTx infusions produced an initial state of cardiovascular and sympathetic nervous system activation in intact and SAD rats. Subsequent to peak LeTx-induced increases in arterial blood pressure, intact rats demonstrated a marked hypotension that was accompanied by significant reductions in SND (renal and splenic) and heart rate (HR) from peak levels. After peak LeTx-induced pressor and sympathoexcitatory responses in SAD rats, MAP, SND (renal, splenic, and adrenal), and HR were progressively and significantly reduced, supporting the hypothesis that LeTx alters the central regulation of sympathetic nerve outflow. These findings demonstrate that the regulation of visceral SND is altered in a complex manner during continuous anthrax LeTx infusions and suggest that sympathetic nervous system dysregulation may contribute to the marked hypotension accompanying B. anthracis infection. PMID:22114180

  6. High precision micro-impulse measurements for micro-thrusters based on torsional pendulum and sympathetic resonance techniques

    NASA Astrophysics Data System (ADS)

    Zhang, Daixian; Wu, Jianjun; Zhang, Rui; Zhang, Hua; He, Zhen

    2013-12-01

    A sympathetic resonance theory is analyzed and applied in a newly developed torsional pendulum to measure the micro-impulse produced by a μN s-class ablative pulsed plasma thruster. According to theoretical analysis on the dynamical behaviors of a torsional pendulum, the resonance amplification effect of micro-signals is presented. In addition, a new micro-impulse measurement method based on sympathetic resonance theory is proposed as an improvement of the original single pulse measurement method. In contrast with the single pulse measurement method, the advantages of sympathetic resonance method are significant. First, because of the magnification of vibration signals due to resonance processes, measurement precision for the sympathetic resonance method becomes higher especially in reducing reading error. With an increase in peak number, the relative errors induced by readout of voltage signals decrease to approximately ±1.9% for the sympathetic resonance mode, whereas the relative error in single pulse mode is estimated as ±13.4%. Besides, by using the resonance amplification effect the sympathetic resonance method makes it possible to measure an extremely low-impulse beyond the resolution of a thrust stand without redesigning or purchasing a new one. Moreover, because of the simple operational principle and structure the sympathetic resonance method is much more convenient and inexpensive to be implemented than other high-precision methods. Finally, the sympathetic resonance measurement method can also be applied in other thrust stands to improve further the ability to measure the low-impulse bits.

  7. High precision micro-impulse measurements for micro-thrusters based on torsional pendulum and sympathetic resonance techniques.

    PubMed

    Zhang, Daixian; Wu, Jianjun; Zhang, Rui; Zhang, Hua; He, Zhen

    2013-12-01

    A sympathetic resonance theory is analyzed and applied in a newly developed torsional pendulum to measure the micro-impulse produced by a μN s-class ablative pulsed plasma thruster. According to theoretical analysis on the dynamical behaviors of a torsional pendulum, the resonance amplification effect of micro-signals is presented. In addition, a new micro-impulse measurement method based on sympathetic resonance theory is proposed as an improvement of the original single pulse measurement method. In contrast with the single pulse measurement method, the advantages of sympathetic resonance method are significant. First, because of the magnification of vibration signals due to resonance processes, measurement precision for the sympathetic resonance method becomes higher especially in reducing reading error. With an increase in peak number, the relative errors induced by readout of voltage signals decrease to approximately ±1.9% for the sympathetic resonance mode, whereas the relative error in single pulse mode is estimated as ±13.4%. Besides, by using the resonance amplification effect the sympathetic resonance method makes it possible to measure an extremely low-impulse beyond the resolution of a thrust stand without redesigning or purchasing a new one. Moreover, because of the simple operational principle and structure the sympathetic resonance method is much more convenient and inexpensive to be implemented than other high-precision methods. Finally, the sympathetic resonance measurement method can also be applied in other thrust stands to improve further the ability to measure the low-impulse bits. PMID:24387474

  8. Properties of postganglionic sympathetic neurons with axons in the right thoracic vagus.

    PubMed

    Bałkowiec, A; Szulczyk, P

    1992-01-01

    The resting and reflex-evoked activities of single postganglionic sympathetic neurons with axons in the right thoracic vagus were tested in chloralose-anaesthetized cats. The properties of a majority of neurons were found to be similar. Cardiac- and inspiration-related rhythmicities were present in the resting activity of sympathetic neurons. Their resting activity was not affected by hyperventilation which abolished phrenic nerve discharges. Systemic hypoxia (2 min; 8% O2 in N2) increased the activity of the neurons more effectively in the deafferented state than when both sinus nerves remained intact. Injection of 0.1 ml 1 M sodium bicarbonate saturated with CO2, which activates peripheral chemoreceptors in the right or left carotid sinus, usually evoked a decrease in sympathetic activity in animals with both sinus nerves intact. We concluded that activation of peripheral chemoreceptors may inhibit the activity of the sympathetic neurons with axons in the right thoracic vagus. We suggest that the described sympathetic neurons may be a functionally homogeneous population which may innervate the conducting system of the heart. The close localization of sympathetic and parasympathetic axons in the vagus nerve may facilitate sympathetic-parasympathetic interaction at the level of their endings in the heart. PMID:1584420

  9. 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

  10. Single-dose Intramuscular Injection Toxicology of Danggui Pharmacopuncture (DGP) in Sprague-Dawley Rats

    PubMed Central

    Sun, SeungHo; Jeong, JongJin; Park, Sunju; Lee, KwangHo; Yu, JunSang; Seo, Hyung-Sik; Kwon, KiRok

    2015-01-01

    Objectives: The purpose of the study is to assess both the approximate lethal dose and the single dose intramuscular injection toxicity of Danggui (Angelica gigantis radix) pharmacopuncture (DGP) in Sprague-Dawley (SD) rats. Methods: The experiments were conducted at the good laboratory practice (GLP) laboratory, Biotoxtech Co., which is a laboratory approved by the ministry of food and drug safety (MFDS). The study was performed according to the GLP regulation and the toxicity test guidelines of the MFDS (2009) after approval of the institutional animal care and use committee of Biotoxtech. Single doses of DGP were injected intramuscularly into the rats in three test groups of 6 week old SD rats (5 male and 5 female rats per groups) in the amounts of 0.1, 0.5, and 1.0 mL/animal for groups 2, 3, and 4, respectively, and normal saline solution in the amount of 1.0 mL/animal was injected intramuscularly into the rats (5 male and 5 female rats) in the control group. Observations of the general symptoms and weight measurements were performed during the 14 day observation period after the injection. Hematologic and serum biochemical examination, necropsy, and a local tolerance test at the injection site were done after the observation period. Results: No death was observed in three test groups (0.1, 0.5 and 1.0 mL/animal group). In addition, the injection of DGP had no effect on general symptoms, weights, hematologic and serum biochemical examination, and necropsy. The results from the local tolerance tests at injection site showed no treatment related effects in the SD rats. Conclusion: The results of single dose intramuscular injection of DGP suggest that the approximate lethal dose is above 1.0 mL/animal for both male and female SD rats and that intramuscular injection of DGP may be safe. PMID:25830059

  11. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation.

    PubMed

    Darios, Emma S; Barman, Susan M; Orer, Hakan S; Morrison, Shaun F; Davis, Robert P; Seitz, Bridget M; Burnett, Robert; Watts, Stephanie W

    2015-05-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  12. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation

    PubMed Central

    Darios, Emma S.; Barman, Susan M.; Orer, Hakan S.; Morrison, Shaun F.; Davis, Robert P.; Seitz, Bridget M.; Burnett, Robert; Watts, Stephanie W.

    2015-01-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101 ± 4 to 63 ± 3 mm Hg during slow infusion of 5-HT (25 μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity was unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30 nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  13. Single and Repeated Ultra-Rapid Detoxification Prevents Cognitive Impairment in Morphine Addicted Rats: A Privilege for Single Detoxification

    PubMed Central

    Ghamati, Leila; Hajali, Vahid; Sheibani, Vahid; Esmaeilpour, Khadijeh; Sepehri, Gholamreza; Shojaee, Mojtaba

    2014-01-01

    Background Opioids have been shown to affect learning and memory processes. Different protocols of morphine withdrawal can substantially vary in their success to prevent opioid induced impairments of cognitive performance. In the present study, we report the effects of single and repetitive ultra-rapid detoxification (URD) on spatial learning and memory in morphine addicted rats. Methods Morphine (10 mg/kg) was intraperitoneally (IP) injected in male rats once a day over one week and after which they were detoxified with naloxone administration under anesthesia. For the repetitive procedure, a second one week morphine treatment with a second subsequent detoxification was performed. Control groups received an equivalent volume of saline injections. Spatial learning and memory was evaluated using the Morris water maze (MWM) task. Findings Both protocols of morphine administration resulted in a severe spatial memory impairment that could be significantly prevented by both single and repetitive URD. However, memory abilities in animals treated with repetitive URD were still significantly lower than in animals of the corresponding control group. Alterations in motor activity or sensory-motor coordination between morphine treated and control animals could be ruled out by comparing swimming speed and visible platform performances that were not different between groups. Thus, URD and, specifically single URD, can prevent the spatial memory impairments in addicted rats. Conclusion As opioid addiction is an extending and serious concern in many societies, these findings may have clinical values and therapeutic implications for patients who experience multiple opioid relapses. PMID:25140218

  14. Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons

    PubMed Central

    Kruse, Martin; Vivas, Oscar; Traynor-Kaplan, Alexis

    2016-01-01

    In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons. SIGNIFICANCE STATEMENT Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2 in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons. PMID:26818524

  15. Sympathetic neurons can produce and respond to interleukin 6

    PubMed Central

    März, Pia; Cheng, Jr-Gang; Gadient, Reto A.; Patterson, Paul H.; Stoyan, Tanja; Otten, Uwe; Rose-John, Stefan

    1998-01-01

    Neuronal expression of cytokines is an area of active investigation in the contexts of development, disease, and normal neural function. Although cultured rat sympathetic neurons respond very weakly to exogenous interleukin 6 (IL-6), we find that addition of soluble IL-6 receptor (sIL-6R) and IL-6 enhances neuronal survival in the absence of nerve growth factor. Neutralizing monoclonal antibodies against IL-6 block these effects. Addition of IL-6 and sIL-6R also induces a subset of neuropeptide and transmitter synthetic enzyme mRNAs identical to that demonstrated for leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Both of these effects are duplicated by addition of a highly active fusion protein of sIL-6R and IL-6, covalently linked by a flexible peptide chain, which is designated H-IL-6. In addition, we show that sympathetic neurons produce IL-6. In situ hybridization indicates a neuronal localization of IL-6 mRNA in superior cervical ganglia, and bioactive IL-6 protein is detected in ganglion culture supernatants. Interestingly, the IL-6 produced by sympathetic neurons does not lead to survival of these cells in culture unless sIL-6R is added. Thus, sympathetic neurons can produce IL-6 and may respond to it in an autocrine/paracrine manner if sIL-6R is present. Moreover, the prior findings of sIL-6R in serum and inflammatory fluids now have added interest in the context of neuro–immune interactions. PMID:9501249

  16. Chemoreflexes, Sleep Apnea, and Sympathetic Dysregulation

    PubMed Central

    Mansukhani, Meghna P.; Kara, Tomas; Caples, Sean; Somers, Virend K.

    2014-01-01

    Obstructive sleep apnea (OSA) and hypertension are closely linked conditions. Disordered breathing events in OSA are characterized by increasing efforts against an occluded airway whilst asleep, resulting in a marked sympathetic response. This is predominantly due to hypoxemia activating the chemoreflexes, resulting in reflex increases in sympathetic neural outflow. In addition, apnea, and the consequent lack of inhibition of the sympathetic system that occurs with lung inflation during normal breathing, potentiates central sympathetic outflow. Sympathetic activation persists into the daytime, and is thought to contribute to hypertension and other adverse cardiovascular outcomes. This review discusses chemoreflex physiology and sympathetic modulation during normal sleep, as well as the sympathetic dysregulation seen in OSA, its extension into wakefulness, and changes after treatment. Evidence supporting the role of the peripheral chemoreflex in the sympathetic dysregulation seen in OSA, including in the context of co-morbid obesity, metabolic syndrome and systemic hypertension is reviewed. Finally, alterations in cardiovascular variability and other potential mechanisms that might play a role in the autonomic imbalance seen in OSA are also discussed. PMID:25097113

  17. 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

  18. Sympathetic ophthalmia complicating helium ion irradiation of a choroidal melanoma

    SciTech Connect

    Fries, P.D.; Char, D.H.; Crawford, J.B.; Waterhouse, W.

    1987-11-01

    Sympathetic ophthalmia was diagnosed 49 months after helium ion irradiation of a left choroidal melanoma. The patient maintained good vision until 18 months after therapy, when she developed neovascular glaucoma. This complication required multiple therapeutic procedures, including topical anti-inflammatory and antiglaucomatous drops, 360 degrees peripheral panretinal cryoblation, and a single 180 degrees application of inferior cyclocryotherapy over a 2 1/2-year period. Four weeks after the cyclocryotherapy, inflammation was noted in both eyes, and, one month later, enucleation of the left sympathogenic eye was performed. Serial histopathologic sections showed a full-thickness, fibrovascular, scleral scar and tantalum marker ring suture without uveal incarceration. Penetrating surgical trauma, a uveal melanoma, and multiple nonpenetrating treatments resulted in the development of sympathetic ophthalmia.

  19. Single Landmark Learning in Rats: Sex Differences in a Navigation Task

    ERIC Educational Resources Information Center

    Forcano, L.; Santamaria, J.; Mackintosh, N. J.; Chamizo, V. D.

    2009-01-01

    In Experiments 1 and 2, rats were trained in a Morris pool to find a hidden platform located some distance away from a single landmark. Males learned to swim to the platform faster than females, but on test trials without the platform, males, unlike females, spent less time in the platform quadrant of the pool in the second half of each test trial…

  20. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    ERIC Educational Resources Information Center

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  1. 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

  2. Simple method for the preparation of single cell suspensions from normal and tumorous rat colonic mucosa.

    PubMed Central

    Perret, V; Lev, R; Pigman, W

    1977-01-01

    Viable single cell suspensions from rat colonic epithelium were obtained by using phosphate buffered saline containing 0-2 M mannitol. The method, which requires no prior enzyme treatment, provides undamaged cells in high yield within one hour. The procedure was also applied to neoplastic rat colonic tissue, which was induced by repeated intrarectal infusion of N-methyl-N-nitrosourea. Comparison between normal and neoplastic cells has shown that the latter have a higher nucleus: cytoplasm ratio and a higher metabolic activity. Images Figure PMID:873323

  3. [Characteristics of the rat behavior following single and multiple exposures of the hypoglycemic insulin doses].

    PubMed

    Shestakova, S A; Eliseeva, A P; Lebedev, A A; Shabaev, V V; Makarova, T M; Klimenko, V M

    2001-10-01

    Rats behaviour in the "open field" changed in 2 hrs after a single episode of hypoglycaemia was abolished with glucose whereas no changes occurred in their stereotyped behaviour and intraspecies interaction. In 24 hrs quantitative parameters of the "open field" behaviour normalised although the behaviour still had an altered structure. At the same time, amphetamine-induced stereotyped behaviour's indices became reduced. These and other findings suggest some deeper behavioural changes in rats during their recovery from repeated hypoglycaemic episodes and absence of synchronisation of the insulin effects. PMID:11767449

  4. Patterning of sympathetic nerve activity in response to vestibular stimulation

    NASA Technical Reports Server (NTRS)

    Kerman, I. A.; McAllen, R. M.; Yates, B. J.

    2000-01-01

    Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.

  5. Short-term diabetic hyperglycemia suppresses celiac ganglia neurotransmission, thereby impairing sympathetically mediated glucagon responses.

    PubMed

    Mundinger, Thomas O; Cooper, Ellis; Coleman, Michael P; Taborsky, Gerald J

    2015-08-01

    Short-term hyperglycemia suppresses superior cervical ganglia neurotransmission. If this ganglionic dysfunction also occurs in the islet sympathetic pathway, sympathetically mediated glucagon responses could be impaired. Our objectives were 1) to test for a suppressive effect of 7 days of streptozotocin (STZ) diabetes on celiac ganglia (CG) activation and on neurotransmitter and glucagon responses to preganglionic nerve stimulation, 2) to isolate the defect in the islet sympathetic pathway to the CG itself, and 3) to test for a protective effect of the WLD(S) mutation. We injected saline or nicotine in nondiabetic and STZ-diabetic rats and measured fos mRNA levels in whole CG. We electrically stimulated the preganglionic or postganglionic nerve trunk of the CG in nondiabetic and STZ-diabetic rats and measured portal venous norepinephrine and glucagon responses. We repeated the nicotine and preganglionic nerve stimulation studies in nondiabetic and STZ-diabetic WLD(S) rats. In STZ-diabetic rats, the CG fos response to nicotine was suppressed, and the norepinephrine and glucagon responses to preganglionic nerve stimulation were impaired. In contrast, the norepinephrine and glucagon responses to postganglionic nerve stimulation were normal. The CG fos response to nicotine, and the norepinephrine and glucagon responses to preganglionic nerve stimulation, were normal in STZ-diabetic WLD(S) rats. In conclusion, short-term hyperglycemia's suppressive effect on nicotinic acetylcholine receptors of the CG impairs sympathetically mediated glucagon responses. WLD(S) rats are protected from this dysfunction. The implication is that this CG dysfunction may contribute to the impaired glucagon response to insulin-induced hypoglycemia seen early in type 1 diabetes. PMID:26037249

  6. Reflex sympathetic dystrophy following traumatic myelopathy.

    PubMed

    Wainapel, S F

    1984-04-01

    Two cases of reflex sympathetic dystrophy in the upper extremity of patients with traumatic cervical spinal cord injuries are reported. Both patients had very incomplete lesions with early neurological recovery, suggesting an underlying central cord syndrome. Although reflex sympathetic dystrophy is often seen following stroke, it has only rarely been documented in traumatic myelopathy, and it should be considered in the differential diagnosis of unexplained pain syndromes in the extremities of paraplegic or quadriplegic patients. PMID:6728500

  7. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

    PubMed

    Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

    2015-05-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

  8. Central oscillators responsible for sympathetic nerve discharge.

    PubMed

    Gebber, G L

    1980-08-01

    The current state of knowledge concerning central mechanisms responsible for the generation of background discharges in sympathetic nerves is examined. It is apparent from recent investigations that the classic concept of a randomly discharging and diffusely organized central network onto which rhythms (cardiac- and respiratory-related) are imposed by extrinsic inputs has not passed the test of time. Rather, brain stem as well as spinal networks that govern the discharges of sympathetic nerves are inherently capable of rhythm generation. Sympathetic nerve rhythms inherent to the central nervous system imply the existence of neuronal circuits that are capable of oscillatory activity. Central oscillators provide a mechanism for synchronization of the activity of populations of sympathetic neurons in the absence of periodic input from sources extrinsic to the central nervous system. Indeed, the thesis is developed that, rather than creating rhythms in sympathetic nerve discharge, the function of periodic input from extrinsic sources such as the baroreceptors is to entrain rhythms of central origin. Finally, the problems associated with the identification of neuronal types that comprise central oscillators which govern the discharges of sympathetic nerves are discussed. PMID:6996496

  9. Pulmonary Responses of Sprague-Dawley Rats in Single Inhalation Exposure to Graphene Oxide Nanomaterials

    PubMed Central

    Han, Sung Gu; Kim, Jin Kwon; Shin, Jae Hoon; Hwang, Joo Hwan; Lee, Jong Seong; Kim, Tae-Gyu; Lee, Ji Hyun; Lee, Gun Ho; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il Je

    2015-01-01

    Graphene is receiving increased attention due to its potential widespread applications in future. However, the health effects of graphene have not yet been well studied. Therefore, this study examined the pulmonary effects of graphene oxide using male Sprague-Dawley rats and a single 6-hour nose-only inhalation technique. Following the exposure, the rats were allowed to recover for 1 day, 7 days, or 14 days. A total of three groups were compared: control (fresh air), low concentration (0.46 ± 0.06 mg/m3), and high concentration (3.76 ± 0.24 mg/m3). The exposure to graphene oxide did not induce significant changes in the body weights, organ weights, and food consumption during the 14 days of recovery time. The microalbumin and lactate dehydrogenase levels in the bronchoalveolar lavage (BAL) fluid were not significantly changed due to the exposure. Similarly, total cell count, macrophages, polymorphonuclear leukocytes, and lymphocytes were not significantly altered in the BAL fluid. Plus, the histopathological examination of the rat lungs only showed an uptake of graphene oxide in the alveolar macrophages of the high-concentration group. Therefore, these results demonstrate that the single inhalation exposure to graphene oxide induce minimal toxic responses in rat lungs at the concentrations and time points used in the present study. PMID:26295037

  10. Depression Increases Sympathetic Activity and Exacerbates Myocardial Remodeling after Myocardial Infarction: Evidence from an Animal Experiment

    PubMed Central

    Liu, Tao; Yuan, Xiaoran; Ruan, Bing; Sun, Lifang; Tang, Yanhong; Yang, Bo; Hu, Dan; Huang, Congxin

    2014-01-01

    Depression is an independent risk factor for cardiovascular events and mortality in patients with myocardial infarction (MI). Excessive sympathetic activation and serious myocardial remodeling may contribute to this association. The aim of this study was to discuss the effect of depression on sympathetic activity and myocardial remodeling after MI. Wild-type (WT) rats were divided into a sham group (Sham), a myocardial infarction group (MI), a depression group (D), and a myocardial infarction plus depression group (MI+D). Compared with controls, the MI+D animals displayed depression-like behaviors and attenuated body weight gain. The evaluation of sympathetic activity showed an increased level in plasma concentrations of epinephrine and norepinephrine and higher expression of myocardial tyrosine hydroxylase in the MI+D group than the control groups (p<0.05 for all). Cardiac function and morphologic analyses revealed a decreased fractional shortening accompanied by increased left ventricular dimensions, thinning myocardium wall, and reduced collagen repair in the MI+D group compared with the MI group (p<0.05 for all). Frequent premature ventricular contractions, prolonged QT duration and ventricular repolarization duration, shorted effective refractory period, and increased susceptibility to ventricular arrhythmia were displayed in MI+D rats. These results indicate that sympathetic hyperactivation and exacerbated myocardial remodeling may be a plausible mechanism linking depression to an adverse prognosis after MI. PMID:25036781

  11. 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. PMID:25784543

  12. 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

  13. REPRODUCTIVE TOXICITY OF A SINGLE DOSE OF 1,3-DINITROBENZENE IN TWO AGES OF YOUNG ADULT MALE RATS

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-Dinitrobenzene (M-DNB). oung adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, ...

  14. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  15. Metabolic and morphologic properties of single muscle fibers in the rat after spaceflight, Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Miu, B.; Martin, T. P.; Roy, R. R.; Oganov, V.; Ilyina-Kakueva, E.; Marini, J. F.; Leger, J. J.; Bodine-Fowler, S. C.; Edgerton, V. R.

    1990-01-01

    The adaptation of a slow (soleus, Sol) and a fast (medial gastrocnemius, MG) skeletal muscle to spaceflight was studied in five young male rats. The flight period was 12.5 days and the rats were killed approximately 48 h after returning to 1 g. Five other rats that were housed in cages similar to those used by the flight rats were maintained at 1 g for the same period of time to serve as ground-based controls. Fibers were classified as dark or light staining for myosin adenosine triphosphatase (ATPase). On the average, the fibers in the Sol of the flight rats atrophied twice as much as those in the MG. Further, the fibers located in the deep (close to the bone and having the highest percentage of light ATPase and high oxidative fibers in the muscle cross section) region of the MG atrophied more than the fibers located in the superficial (away from the bone and having the lowest percentage of light ATPase and high oxidative fibers in the muscle cross-section) region of the muscle. Based on quantitative histochemical assays of single muscle fibers, succinate dehydrogenase (SDH) activity per unit volume was unchanged in fibers of the Sol and MG. However, in the Sol, but not the MG, the total amount of SDH activity in a 10-microns-thick section of a fiber decreased significantly in response to spaceflight. Based on population distributions, it appears that the alpha-glycerophosphate dehydrogenase (GPD) activities were elevated in the dark ATPase fibers in the Sol, whereas the light fibers in the Sol and both fiber types in the MG did not appear to change. The ratio of GPD to SDH activities increased in the dark (but not light) fibers of the Sol and was unaffected in the MG. Immunohistochemical analyses indicate that approximately 40% of the fibers in the Sol of flight rats expressed a fast myosin heavy chain compared with 22% in control rats. Further, 31% of the fibers in the Sol of flight rats expressed both fast and slow myosin heavy chains compared with 8% in

  16. Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

    PubMed Central

    Manni, Luigi; Lundeberg, Thomas; Holmäng, Agneta; Aloe, Luigi; Stener-Victorin, Elisabet

    2005-01-01

    Background Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. Methods In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). Results It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR. Conclusion The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS. PMID:15941472

  17. Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

    PubMed

    Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David

    2014-01-01

    Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

  18. Delayed thermoregulatory changes in the immature rat following a single injection of ethanol.

    PubMed

    Spiers, D E; Fusco, L E

    1992-02-01

    Adult rats exhibit rebound hyperthermia within 24 hr following a single injection of ethanol (EtOH). Tests were conducted to determine whether similar changes in thermoregulatory ability occur in the immature rat. Animals were administered saline or EtOH (4 g/kg BW; intraperitoneally) at 2 to 3, 8 to 9, or 14 to 15 days of age. Littermates were handled or left undisturbed with the dams to serve as controls. All rats were tested at 24 or 48 hr post-treatment to measure steady-state colonic temperature (Tco), tail skin temperature and metabolic rate (MR) at both thermoneutral and cold ambient temperatures (Tas). The youngest group exhibited no delayed change in body temperature or MR at 24 or 48 hr post-treatment with EtOH. Likewise, thermoregulatory ability of rats pretreated with EtOH at 8 or 9 or 14 to 15 days of age was not significantly different from controls when tested 24 hr post-treatment at thermoneutral Ta. In contrast, Tco of EtOH-treated rats in the two older age groups was 1 degree C above control level when tested 24 hr post-treatment at cold Ta. This Tco response can be explained by differences in heat transfer to the tail and MR. No altered response to cold Ta was found at 48 hr postinjection, indicating recovery from the EtOH effect. A single injection with EtOH at 2 to 15 days of age results in a change in Tco, which is dependent on postinjection time, age, and Ta. PMID:1313662

  19. Quantitative determination of dopamine in single rat pheochromocytoma cells by microchip electrophoresis with only one high-voltage power supply.

    PubMed

    Sha, Cuicui; Fan, Yuejuan; Cheng, Jieke; Cheng, Han

    2015-07-01

    We developed a method for the direct identification of dopamine in single cultured rat pheochromocytoma cells by capillary electrophoresis using an end-channel carbon fiber nanoelectrode amperometric detector. The operation mode was designed to achieve single-cell injection and lysis in microfluidic chip electrophoresis with only one high-voltage power supply. The separation and detection conditions were optimized. Four catecholamines were baseline-separated and determined with this system, and the cell density and liquid height of the reservoirs were accommodated for single cell loading, docking and analysis. The microchip capillary electrophoresis system was successfully applied to determine dopamine in single cultured rat pheochromocytoma cells. PMID:25893961

  20. 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

  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. DEATH OF INTERMEDIOLATERAL SPINAL CORD NEURONS FOLLOWS SELECTIVE COMPLEMENT-MEDIATED DESTRUCTION OF PERIPHERAL PREGANGLIONIC SYMPATHETIC TERMINALS BY ACETYLCHOLINESTERASE ANTIBODIES

    EPA Science Inventory

    Systemically administered antibodies to acetylcholinesterase (ACHE) cause a selective complement-mediated destruction of preganglionic sympathetic nerve terminals. o assess neurologic integrity, rats given murine monoclonal AChE-antibodies or normal mouse IgG (1.5 mg,i.v.) were e...

  3. Intramuscular Single-dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Lee, Kwang-Ho; Sun, Seung-Ho; Yu, Jun-Sang; Kwon, Ki-Rok

    2015-01-01

    Objectives: Bufonis venonum (BV) is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP) and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. Results: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. Conclusion: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal. PMID:26998390

  4. Single- and repeated-dose toxicities of aloe fermentation products in rats

    PubMed Central

    Kim, Hyun-Kyoung; Baik, Soon-Ok; Choi, Soo-Young; Lee, Jae-Young

    2011-01-01

    In this study, aloe fermentation products were derived from mycelia from 3 mushrooms: Ganoderma lucidum (AG), Hericium erinaceum (AH), and Phellinus linteus (AP). Levels of aloin A and B increased with fermentation time. The highest levels were measured on the fifth day of fermentation. β-Glucan levels decreased with fermentation time. The safety of aloe fermentation products were examined in male and female Sprague-Dawley rats. Rats were orally administered the three aloe fermentation products at dose levels of 1, 2 or 5 g/kg for single-dose toxicity test and 0.5, 1, or 2 g/kg for repeated-dose toxicity test. There were no significant differences in body weight gain between vehicle control and AG-, AH- or AP-treated rats. Also, significant changes in daily feed intake and water consumption were not observed. In hematological analysis, none of the parameters were affected by aloe fermentation products with mushroom mycelia. This suggests that there are no negative effects on homeostasis and immunity. In blood biochemistry analysis, none of the markers were affected by feeding rats with AG, AH or AP. Similarly, there were no significant effects on markers for liver, kidney, skeletal and heart muscle functions. No remarkable lesions were observed in these organs at histopathology. Since there were no adverse effects of AG, AH and AP in single- or repeated-dose toxicity tests, even at higher doses than normal, we conclude that the aloe fermentation products with mushroom mycelia possess long-term safety and could be candidates as multifunctional nutrients for the improvement of intestinal function and immunity. PMID:21998613

  5. Altered Differential Control of Sympathetic Outflow Following Sedentary Conditions: Role of Subregional Neuroplasticity in the RVLM

    PubMed Central

    Subramanian, Madhan; Mueller, Patrick J.

    2016-01-01

    Despite the classically held belief of an “all-or-none” activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA) can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA) but not lumbar SNA (LSNA) to activation of the rostral ventrolateral medulla (RVLM) in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA following activation of the rostral RVLM. To test this hypothesis, groups of physically active (10–12 weeks on running wheels) or sedentary, male Sprague-Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM) into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not LSNA responses and SSNA responses were enhanced at more central and rostral sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with enhanced dendritic branching in rostral RVLM observed previously. Identifying structural and functional neuroplasticity in specific populations of RVLM neurons may help identify new treatments for cardiovascular diseases, known to be more prevalent in sedentary individuals. PMID:27486405

  6. Hypothalamic Nesfatin-1 Stimulates Sympathetic Nerve Activity via Hypothalamic ERK Signaling.

    PubMed

    Tanida, Mamoru; Gotoh, Hitoshi; Yamamoto, Naoki; Wang, Mofei; Kuda, Yuhichi; Kurata, Yasutaka; Mori, Masatomo; Shibamoto, Toshishige

    2015-11-01

    Nesfatin-1 acts on the hypothalamus and regulates the autonomic nervous system. However, the hypothalamic mechanisms of nesfatin-1 on the autonomic nervous system are not well understood. In this study, we found that intracerebroventricular (ICV) administration of nesfatin-1 increased the extracellular signal-regulated kinase (ERK) activity in rats. Furthermore, the activity of sympathetic nerves, in the kidneys, liver, and white adipose tissue (WAT), and blood pressure was stimulated by the ICV injection of nesfatin-1, and these effects were abolished owing to pharmacological inhibition of ERK. Renal sympathoexcitatory and hypertensive effects were also observed with nesfatin-1 microinjection into the paraventricular hypothalamic nucleus (PVN). Moreover, nesfatin-1 increased the number of phospho (p)-ERK1/2-positive neurons in the PVN and coexpression of the protein in neurons expressing corticotropin-releasing hormone (CRH). Pharmacological blockade of CRH signaling inhibited renal sympathetic and hypertensive responses to nesfatin-1. Finally, sympathetic stimulation of WAT and increased p-ERK1/2 levels in response to nesfatin-1 were preserved in obese animals such as rats that were fed a high-fat diet and leptin receptor-deficient Zucker fatty rats. These findings indicate that nesfatin-1 regulates the autonomic nervous system through ERK signaling in PVN-CRH neurons to maintain cardiovascular function and that the antiobesity effect of nesfatin-1 is mediated by hypothalamic ERK-dependent sympathoexcitation in obese animals. PMID:26310564

  7. A single resistance exercise session improves myocardial contractility in spontaneously hypertensive rats.

    PubMed

    Fernandes, A A; Faria, T de O; Ribeiro Júnior, R F; Costa, G P; Marchezini, B; Silveira, E A; Angeli, J K; Stefanon, I; Vassallo, D V; Lizardo, J H

    2015-09-01

    Resistance training evokes myocardial adaptation; however, the effects of a single resistance exercise session on cardiac performance are poorly understood or investigated. This study aimed to investigate the effects of a single resistance exercise session on the myocardial contractility of spontaneously hypertensive rats (SHRs). Male 3-month-old SHRs were divided into two groups: control (Ct) and exercise (Ex). Control animals were submitted to sham exercise. Blood pressure was measured in conscious rats before the exercise session to confirm the presence of arterial hypertension. Ten minutes after the exercise session, the animals were anesthetized and killed, and the hearts were removed. Cardiac contractility was evaluated in the whole heart by the Langendorff technique and by isometric contractions of isolated left ventricular papillary muscles. SERCA2a, phospholamban (PLB), and phosphorylated PLB expression were investigated by Western blot. Exercise increased force development of isolated papillary muscles (Ex=1.0±0.1 g/mg vs Ct=0.63±0.2 g/mg, P<0.05). Post-rest contraction was greater in the exercised animals (Ex=4.1±0.4% vs Ct=1.7±0.2%, P<0.05). Papillary muscles of exercised animals developed greater force under increasing isoproterenol concentrations (P<0.05). In the isolated heart, exercise increased left ventricular isovolumetric systolic pressure (LVISP; Δ +39 mmHg; P<0.05) from baseline conditions. Hearts from the exercised rats presented a greater response to increasing diastolic pressure. Positive inotropic intervention to calcium and isoproterenol resulted in greater LVISP in exercised animals (P<0.05). The results demonstrated that a single resistance exercise session improved myocardial contractility in SHRs. PMID:26176315

  8. A single resistance exercise session improves myocardial contractility in spontaneously hypertensive rats

    PubMed Central

    Fernandes, A.A.; Faria, T. de O.; Ribeiro, R.F.; Costa, G.P.; Marchezini, B.; Silveira, E.A.; Angeli, J.K.; Stefanon, I.; Vassallo, D.V.; Lizardo, J.H.

    2015-01-01

    Resistance training evokes myocardial adaptation; however, the effects of a single resistance exercise session on cardiac performance are poorly understood or investigated. This study aimed to investigate the effects of a single resistance exercise session on the myocardial contractility of spontaneously hypertensive rats (SHRs). Male 3-month-old SHRs were divided into two groups: control (Ct) and exercise (Ex). Control animals were submitted to sham exercise. Blood pressure was measured in conscious rats before the exercise session to confirm the presence of arterial hypertension. Ten minutes after the exercise session, the animals were anesthetized and killed, and the hearts were removed. Cardiac contractility was evaluated in the whole heart by the Langendorff technique and by isometric contractions of isolated left ventricular papillary muscles. SERCA2a, phospholamban (PLB), and phosphorylated PLB expression were investigated by Western blot. Exercise increased force development of isolated papillary muscles (Ex=1.0±0.1 g/mg vs Ct=0.63±0.2 g/mg, P<0.05). Post-rest contraction was greater in the exercised animals (Ex=4.1±0.4% vs Ct=1.7±0.2%, P<0.05). Papillary muscles of exercised animals developed greater force under increasing isoproterenol concentrations (P<0.05). In the isolated heart, exercise increased left ventricular isovolumetric systolic pressure (LVISP; Δ +39 mmHg; P<0.05) from baseline conditions. Hearts from the exercised rats presented a greater response to increasing diastolic pressure. Positive inotropic intervention to calcium and isoproterenol resulted in greater LVISP in exercised animals (P<0.05). The results demonstrated that a single resistance exercise session improved myocardial contractility in SHRs. PMID:26176315

  9. Single Intravenous-dose Toxicity of Water-soluble Carthami-flos Pharmacopuncture (WCF) in Rats

    PubMed Central

    Jung, Da-jung; Choi, Yoo-min; Kim, Seok-hee; Kim, Jong-uk; Yook, Tae-han

    2014-01-01

    Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Water-soluble Carthami-flos pharmacopuncture (WCF) when used as a single intravenous-dose in 6-week-old, male and female Sprague-Dawley rats. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. 20 female and 20 male Spague-Dawley rats were divided into 4 groups of 5 female and 5 male animals per group. The rats in the three experimental groups received single intravenous injections with 0.125-mL, 0.25-mL and 0.5-mL/animal doses of WCF, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intravenous injection with a 0.5-mL dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, no significant changes in body weight, hematological parameters or clinical chemistry test results between the control group and the experimental groups were observed. Visual inspection after necropsy showed no abnormalities. Histopathological tests on the injected parts showed no significant differences, except for Group 1 females; however, the result was spontaneous generation and had no toxicological meaning because it was not dose-dependent. Therefore, this study showed that WCF had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single intravenous-dose tests of the test substance WCF in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, WCF is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed. PMID:25780707

  10. Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot.

    PubMed

    Fenrich, Keith K; May, Zacincte; Torres-Espín, Abel; Forero, Juan; Bennett, David J; Fouad, Karim

    2016-02-15

    Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury. PMID:26611563

  11. Size and metabolic properties of single muscle fibers in rat soleus after hindlimb suspension

    NASA Technical Reports Server (NTRS)

    Hauschka, Edward O.; Roy, Roland R.; Edgerton, V. Reggie

    1987-01-01

    The effect of 28-day-long hind-limb suspension (HS) combined with 10 daily forceful lengthening contractions of the limb on the morphological and metabolic properties of individual fibers of the soleus was studied in rats, using quantitative histochemical techniques. Compared with nonsuspended controls (CON), soleus wet weights of HS rats were decreased by 49 percent; the fibers staining lightly for myosin ATPase ('light-ATPase' fibers) atrophied more than the 'dark-ATPase' fibers. Single-fiber alpha-glycerophosphate dehydrogenase (GPD) and succinate dehydrogenase (SDH) activities were higher in HS than in CON rats. Daily forceful lengthening contractions did not prevent the HS-induced changes. The results support the view that the soleus fibers can change from a slow-twitch oxidative to a fast-twitch oxidative-glycolytic profile, but rarely to a fast-twitch glycolytic one, and that the SDH and GPD activities per volume of tissue can be increased even when there are severe losses of contractile proteins.

  12. Intestinal permeability of forskolin by in situ single pass perfusion in rats.

    PubMed

    Liu, Zhen-Jun; Jiang, Dong-bo; Tian, Lu-Lu; Yin, Jia-Jun; Huang, Jian-Ming; Weng, Wei-Yu

    2012-05-01

    The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability. PMID:22411728

  13. Single Prolonged Stress Decreases Glutamate, Glutamine, and Creatine Concentrations In The Rat Medial Prefrontal Cortex

    PubMed Central

    Knox, Dayan; Perrine, Shane A.; George, Sophie A.; Galloway, Matthew P.; Liberzon, Israel

    2010-01-01

    Application of Single Prolonged Stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of Post Traumatic Stress Disorder (PTSD). PTSD, in humans, is associated with decreased neural activity in the prefrontal cortex, increased neural activity in the amygdala complex, and reduced neuronal integrity in the hippocampus. However, the extent to which SPS models these aspects of PTSD has not been established. In order to address this, we used high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H MRS) ex vivo to assay levels of neurochemicals critical for energy metabolism (creatine and lactate), excitatory (glutamate and glutamine) and inhibitory (gamma amino butyric acid (GABA)) neurotransmission, and neuronal integrity (N-acetyl aspartate (NAA)) in the medial prefrontal cortex (mPFC), amygdala complex, and hippocampus of SPS and control rats. Glutamate, glutamine, and creatine levels were decreased in the mPFC of SPS rats when compared to controls, which suggests decreased excitatory tone in this region. SPS did not alter the neurochemical profiles of either the hippocampus or amygdala. These data suggest that SPS selectively attenuates excitatory tone, without a disruption of neuronal integrity, in the mPFC. PMID:20546834

  14. Effect of a single injection of high-dose FK506 on lung transplantation in rats.

    PubMed

    Sano, Y; Maruyama, S; Aoe, M; Date, H; Shimizu, N

    1996-01-01

    Orthotopic left lung grafts from Brown Norway (BN) donors were transplanted to Lewis (LEW) rat recipients which had been treated with a single dose of FK506 10mg/kg body weight intramuscularly on postoperative day 3. Although the lungs were rejected with a median survival time of 7 days, with a range of 6-8 days in the untreated controls, maximum survival was prolonged to 60 days. The major adverse effects of this therapy were reduction of feeding, loss of body weight, and diarrhea. One of the 7 rats died on the 21st postoperative day due to anorexia. The effects of this therapy were investigated by histopathological examination and flow cytometric analysis using monoclonal antibodies against rat lymphocytes: OX-39 (anti-interleukin 2 receptor (IL-2R)) and OX-6 (anti-class II MHC). Histopathologically, the lung allografts showed mild perivascular and peribronchiolar cuffs of mononuclear cells, while marked reduction of the thymic medulla with FK506 treatment was also observed. Flow cytometric analysis of the transplanted lung showed no significant changes. Regarding the thymus, the percentages of positive cells labeled with OX-39 and OX-6 were significantly suppressed after this treatment. In the spleen, the number of OX-6-positive cells significantly decreased. The results using this therapy thus suggest that the suppression of IL-2R and MHC class II expression was systemically maintained for a long time. PMID:9017963

  15. A Salicylate Sympathetic Ink from Consumer Chemicals

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 2005

    2005-01-01

    A new sympathetic ink that produces a violet color upon development was developed to develop chemical demonstrations using consumer chemicals. The demonstration was to have a simple, relatively safe reagent system that could be used to make a brightly colored, highly visible "magic sign" for use in science outreach programs.

  16. Detection of single unit activity from the rat vagus using cluster analysis of principal components.

    PubMed

    Horn, Charles C; Friedman, Mark I

    2003-01-30

    In vivo recordings from subdiaphragmatic vagal afferent nerves generally lack the resolution to distinguish single unit activity. Several methods for data acquisition and analysis were combined to produce a high degree of reliability in recording electrophysiological signals from gastrointestinal and hepatic afferent fibers in the rat. Recordings with low noise were achieved by paralysis of the respiratory muscles and by pinning the nerve to a recording platform. Single unit activity was isolated using principal component (PC) analysis and cluster cutting of data in multi-dimensional space (1-3 PCs). Cluster assignments were determined by a semi-automated approach using the k-means algorithm. The accuracy of single unit classification was assessed by checking inter-spike intervals (ISIs) to determine the length of the refractory period, and by cross-correlation analysis to assess whether single units were mistakenly split into more than one cluster. These analyses produced up to four isolated single units from each nerve filament (a bundle of nerve fibers), and typically it was possible to further increase yield by recording from several nerve filaments simultaneously using an array of electrodes. PMID:12573473

  17. Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats

    PubMed Central

    Lee, Kwang-Ho; Yu, JunSang; Sun, Seungho; Kwon, KiRok

    2015-01-01

    Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP) is used. Thus, sweet bee venom (SBV) was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal). Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats. PMID:26389001

  18. Firing Properties of Rat Lateral Mammillary Single Units: Head Direction, Head Pitch, and Angular Head Velocity

    PubMed Central

    Stackman, Robert W.; Taube, Jeffrey S.

    2006-01-01

    Many neurons in the rat anterodorsal thalamus (ADN) and postsubiculum (PoS) fire selectively when the rat points its head in a specific direction in the horizontal plane, independent of the animal’s location and ongoing behavior. The lateral mammillary nuclei (LMN) are interconnected with both the ADN and PoS and, therefore, are in a pivotal position to influence ADN/PoS neurophysiology. To further understand how the head direction (HD) cell signal is generated, we recorded single neurons from the LMN of freely moving rats. The majority of cells discharged as a function of one of three types of spatial correlates: (1) directional heading, (2) head pitch, or (3) angular head velocity (AHV). LMN HD cells exhibited higher peak firing rates and greater range of directional firing than that of ADN and PoS HD cells. LMN HD cells were modulated by angular head velocity, turning direction, and anticipated the rat’s future HD by a greater amount of time (~95 msec) than that previously reported for ADN HD cells (~25 msec). Most head pitch cells discharged when the rostrocaudal axis of the rat’s head was orthogonal to the horizontal plane. Head pitch cell firing was independent of the rat’s location, directional heading, and its body orientation (i.e., the cell discharged whenever the rat pointed its head up, whether standing on all four limbs or rearing). AHV cells were categorized as fast or slow AHV cells depending on whether their firing rate increased or decreased in proportion to angular head velocity. These data demonstrate that LMN neurons code direction and angular motion of the head in both horizontal and vertical planes and support the hypothesis that the LMN play an important role in processing both egocentric and allocentric spatial information. PMID:9787007

  19. Single-dose Toxicity of Water-soluble Ginseng Pharmacopuncture Injected Intramuscularly in Rats

    PubMed Central

    Yu, Junsang; Sun, Seungho; Lee, Kwangho; Kwon, Kirok

    2015-01-01

    Objectives: Radix Ginseng has been traditionally used as an adaptogen that acts on the adrenal cortex and stimulates or relaxes the nervous system to restore emotional and physical balance and to improve well-being in cases of degenerative disease and/or old age. Radix Ginseng has been used for a long time, but the safety of ginseng pharmacopuncture needs testing. This study was done to analyze the single-dose toxicity of water-soluble ginseng pharmacopuncture (GP) intramuscular injections in rats. Methods: All experiments were performed at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). Each group contained 10 Sprague-Dawley rats, 5 males and 5 females. GP was prepared in a sterile room at the Korean Pharmacopuncture Institute under regulations of Good Manufacturing Practice (GMP). GP dosages were 0.1, 0.5 and 1.0 mL for the experimental groups; normal saline was administered to the control group. The animals general condition was examined daily for 14 days, and the rats were weighed on the starting day and at 3, 7 and 14 days after administration of the pharmacopuncture. Hematological and biochemistry tests and autopsies were done to test the toxicological effect of GP after 14 days. This study was performed with approval from the Institutional Animal Ethics Committee of Biotextech. Results: No deaths were found in this single-dose toxicity test of intramuscular injections of GP, and no significant changes in the general conditions, body weights, hematological and biochemistry tests, and autopsies were observed. The local injection site showed no changes. Based on these results, the lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results suggest that GP is relatively safe. Further studies, including a repeated toxicity test, are needed to provide more concrete evidence for the safety of GP. PMID:26120491

  20. Single bout of running exercise changes LC3-II expression in rat cardiac muscle.

    PubMed

    Ogura, Yuji; Iemitsu, Motoyuki; Naito, Hisashi; Kakigi, Ryo; Kakehashi, Chiaki; Maeda, Seiji; Akema, Tatsuo

    2011-11-01

    Macroautophagy (autophagy) is an intracellular catalytic process. We examined the effect of running exercise, which stimulates cardiac work physiologically, on the expression of microtubule-associated protein 1 light chain 3 (LC3)-II, an indicator of autophagy, as well as some autophagy-related proteins in rat cardiac muscle. The left ventricles were taken from rats immediately (0 h), and at 0.5h, 1h or 3h after a single bout of running exercise on a treadmill for 30 min and also from rats in a rest condition. In these samples, we evaluated the level of LC3-II and p62, and the phosphorylation level of mammalian target of rapamycin (mTOR), Akt and AMP-activated protein kinase alpha (AMPKα) by Western blotting. The exercise produced a biphasic change in LC3-II, with an initial decrease observed immediately after the exercise and a subsequent increase 1h thereafter. LC3-II then returned to the rest level at 3h after the exercise. A negative correlation was found between the LC3-II expression and mTOR phosphorylation, which plays a role in inhibiting autophagy. The exercise increased phosphorylation of AMPKα, which stimulates autophagy via suppression of mTOR phosphorylation, immediately after exercise. The level of p62 and phosphorylated Akt was not altered significantly by the exercise. These results suggest for the first time that a single bout of running exercise induces a biphasic change in autophagy in the cardiac muscle. The exercise-induced change in autophagy might be partially mediated by mTOR in the cardiac muscle. PMID:22005460

  1. Changes in contractile properties of skinned single rat soleus and diaphragm fibres after chronic hypoxia.

    PubMed

    Degens, Hans; Bosutti, Alessandra; Gilliver, Sally F; Slevin, Mark; van Heijst, Arno; Wüst, Rob C I

    2010-10-01

    Hypoxia may be one of the factors underlying muscle dysfunction during ageing and chronic lung and heart failure. Here we tested the hypothesis that chronic hypoxia per se affects contractile properties of single fibres of the soleus and diaphragm muscle. To do this, the force-velocity relationship, rate of force redevelopment and calcium sensitivity of single skinned fibres from normoxic rats and rats exposed to 4 weeks of hypobaric hypoxia (410 mmHg) were investigated. The reduction in maximal force (P(0)) after hypoxia (p=0.031) was more pronounced in type IIa than type I fibres and was mainly attributable to a reduction in fibre cross-sectional area (p=0.044). In type IIa fibres this was aggravated by a reduction in specific tension (p=0.001). The maximal velocity of shortening (V (max)) and shape of the force velocity relation (a/P(0)), however, did not differ between normoxic and hypoxic muscle fibres and the reduction in maximal power of hypoxic fibres (p=0.012) was mainly due to a reduction in P(0). In conclusion, chronic hypoxia causes muscle fibre dysfunction which is not only due to a loss of muscle mass, but also to a diminished force generating capacity of the remaining contractile material. These effects are similar in the soleus and diaphragm muscle, but more pronounced in type IIa than I fibres. PMID:20697736

  2. Action of cocaine and chronic sympathetic denervation on vagal escape

    PubMed Central

    Campos, H. A.; Urquilla, P. R.

    1969-01-01

    1. The effect of cocaine has been studied on vagal escape and on the tachycardia due to vagal stimulation in the atropinized dog. All the dogs were submitted to acute cervical section of the spinal cord and acute or chronic sympathetic denervation. 2. Cocaine, 5 mg/kg or 40 μg/kg/min, I.V., induces a significant enhancement of the ventricular escape. The effects of a continuous infusion of cocaine are more reproducible than those of a single injection of the drug. 3. Cocaine, 40 μg/kg/min, I.V., potentiates the tachycardia due to vagal stimulation in the atropinized dog. 4. Chronic thoracic sympathectomy markedly retards the recovery of the ventricular rate from the inhibitory action of the vagus. Under this condition, the infusion of cocaine does not significantly enhance the ventricular escape. 5. These findings suggest that an adrenergic mechanism located at the sympathetic nerves supplying the heart is substantially involved in the phenomenon of vagal escape. PMID:5249864

  3. Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in the male Fischer rat

    SciTech Connect

    Waalkes, M.P.; Rehm, S.; Sass, B.; Konishi, N.; Ward, J.M. )

    1991-06-01

    This study determined tumor incidence in various tissues of male Fischer F344 rats after a single dose of cadmium. Cadmium (as CdCl{sub 2}) was given sc in the dorsal thoracic midline at 30 {mu}mole/kg to 70 8-week old male F344 rats while controls received saline. Rats were observed during the next 90 weeks. Early deaths ({much lt} 32 weeks), due mostly to acute cadmium-induced hepatotoxicity, accounted for 37 of the cadmium-treated rats while no control rats died in the same period. A high incidence of injection site sarcomas (ISS) occurred in the cadmium-treated group while only 1/50 occurred in controls (2%). In fact, ISS were the major cause of morbidity after 35 weeks in cadmium-treated rats. These tumors were mostly fibrosarcomas, although histiocytic and osteogenic sarcomas also occurred. Testicular interstitial cell tumors, which show a very high spontaneous incidence in this strain, were not markedly affected by cadmium. This is in sharp contrast to other strains, such as the Wistar, in which cadmium treatment is reported to cause as much as an eightfold increase in interstitial cell (Leydig cell) tumor incidence. The incidence of large granular lymphocyte (LGL) leukemia, which also occurred frequently in control F344 rats was markedly decreased by cadmium in lymphoid tissues of rats, and this may be related to the suppression of the leukemia.

  4. From one generation to the next: a comprehensive account of sympathetic receptor control in branching arteriolar trees

    PubMed Central

    Al-Khazraji, Baraa K; Saleem, Amani; Goldman, Daniel; Jackson, Dwayne N

    2015-01-01

    The effect of the sympathetic nervous system on blood flow distribution within skeletal muscle microvasculature is conditional upon regional activation of receptors for sympathetic neurotransmitters. Previous studies have shown that proximal arterioles are largely governed by adrenergic activation, whereas it is speculated that distal branches are controlled by peptidergic and purinergic activation. However, no study has systematically evaluated the activation of adrenergic, peptidergic and purinergic receptors in continuously branching arteriolar trees of an individual skeletal muscle model. Therefore, in the present study, sympathetic agonists were used to evaluate the constriction responses along first to fifth order arterioles in continuously branching arteriolar trees of a in vivo rat gluteus maximus muscle preparation with respect to specific activation of receptors for sympathetic neurotransmitters (α1R, α2R, NPY1R and P2X1R). Constriction responses were incorporated into a mathematical blood flow model to estimate the total flow, resistance and red blood cell flow heterogeneity within a computationally reconstructed gluteus maximus arteriolar network. For the first time, the effects of activating receptors for sympathetic neurotransmitters on vasoconstrictor responses and the ensuing haemodynamics in continuously branching arteriolar trees of skeletal muscle were characterized, where proximal arterioles responded most to α1R and α2R adrenergic activation, whereas distal arterioles responded most to Y1R and P2X1R activation. Total flow and resistance changed with activation of all receptors, whereas red blood cell flow heterogeneity was largely affected by peptidergic and purinergic activation in distal arterioles. The reported data highlight the functional consequences of topologically-dependent sympathetic control and may serve as novel input parameters in computational modelling of network flow. Key points The sympathetic nervous system increases

  5. Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses

    SciTech Connect

    Kopp, Eva Katharina; Dekant, Wolfgang

    2009-03-01

    The rodent carcinogen acrylamide (AA) is formed during preparation of starch-containing foods. AA is partly metabolized to the genotoxic epoxide glycidamide (GA). After metabolic processing, the mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), rac-N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) and rac-N-acetyl-S-(1-carbamoyl-moyl-2-hydroxyethyl)-L-cysteine (iso-GAMA) are excreted with urine. In humans, AAMA can be sulfoxidized to AAMA-sulfoxide. The aim of this study was to assess potential species-differences in AA-toxicokinetics in rats and humans after single oral administration of doses similar to the daily human dietary exposure. Male Fischer 344 rats (n = 5/dose group) were administered 20 and 100 {mu}g/kg b.w. {sup 13}C{sub 3}-AA in deionized water via oral gavage. Human subjects (n = 3/gender) were orally administered 0.5 and 20 {mu}g/kg b.w. {sup 13}C{sub 3}-AA with drinking water. Urine samples were collected in intervals for 96 and 94 h, respectively. Urinary concentrations of {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide were monitored by liquid chromatography-tandem mass spectrometry. The recovered urinary metabolites accounted for 66.3% and 70.5% of the 20 and 100 {mu}g/kg b.w. doses in rats and for 71.3% and 70.0% of the 0.5 and 20 {mu}g/kg b.w. doses in humans. In rats, {sup 13}C{sub 3}-AAMA accounted for 33.6% and 38.8% of dose and 32.7% and 31.7% of dose was recovered as {sup 13}C{sub 3}-GAMA; {sup 13}C{sub 3}-AAMA-sulfoxide was not detected in rat urine. In humans, {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide accounted for 51.7% and 49.2%, 6.3% and 6.4% and 13.2% and 14.5% of the applied dose, respectively. The obtained results suggest that the extent of AA bioactivation to GA in humans is lower than in rodents.

  6. Biotransformation of ethanol to ethyl glucuronide in a rat model after a single high oral dosage.

    PubMed

    Wright, Trista H; Ferslew, Kenneth E

    2012-03-01

    Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest that maximum blood EtG (BEtG) concentrations are reached between 3.5 and 5.5h after ethanol administration. This study was undertaken to determine if the Sprague-Dawley (SD) rat biotransforms ethanol to EtG after a single high oral dose of ethanol. SD rats (male, n=6) were gavaged with a single ethanol dose (4 g/kg), and urine was collected for 3 h in metabolic cages, followed by euthanization and collection of heart blood. Blood and urine were analyzed for ethanol and EtG by gas chromatography and enzyme immunoassay. Blood and urine ethanol concentrations were 195±23 and 218±19 mg/dL, whereas BEtG and urine EtG (UEtG) concentrations were 1,363±98 ng equivalents/mL and 210±0.29 mg equivalents/dL (X ± standard error of the mean [S.E.M.]). Sixty-six male SD rats were gavaged ethanol (4 g/kg) and placed in metabolic cages to determine the extent and duration of ethanol to EtG biotransformation and urinary excretion. Blood and urine were collected up to 24 h after administration for ethanol and EtG analysis. Maximum blood ethanol, urine ethanol, and UEtG were reached within 4 h, whereas maximum BEtG was reached 6 h after administration. Maximum concentrations were blood ethanol, 213±20 mg/dL; urine ethanol, 308±34 mg/dL; BEtG, 2,683±145 ng equivalents/mL; UEtG, 1.2±0.06 mg equivalents/mL (X±S.E.M.). Areas under the concentration-time curve were blood ethanol, 1,578 h*mg/dL; urine ethanol, 3,096 h*mg/dL; BEtG, 18,284 h*ng equivalents/mL; and UEtG, 850 h*mg equivalents/dL. Blood ethanol and BEtG levels were reduced to below limits of detection (LODs) within 12 and 18 h after ethanol administration. Urine ethanols were below LOD at 18 h, but UEtG was still detectable at 24h after administration. Our data prove that the SD rat biotransforms ethanol to EtG and excretes both in the urine and suggest that it

  7. Ketamine effects on somatosensory cortical single neurons and on behavior in rats.

    PubMed

    Patel, I M; Chapin, J K

    1990-06-01

    The neurophysiological effects of ketamine were studied at the single-neuron level in the somatosensory cortex of unanesthetized rats behaving in a treadmill movement paradigm. Chronically implanted 25-microns microwire electrodes were used to record spontaneous discharge, sensory responses, and sensorimotor-correlated activity of single neurons before and after ketamine administration. Extracellular action potentials of up to six single neurons were simultaneously recorded for several days, allowing ketamine effects to be tested repeatedly on the same neurons. Videotaped recordings obtained during each experiment were used to measure both the sensorimotor properties of the neurons and the changes in these measures caused by different doses of ketamine. Behaviorally, ketamine produced restless-hyperactive behavior at subanesthetic doses from 5 to 20 mg/kg (intramuscularly). At higher doses (30-50 mg/kg) the rats became cataleptic and immobile after the initial hyperactive period. Whereas the spontaneous rates of most neurons were reduced or unchanged after subanesthetic doses, a subgroup (27% of the total) exhibited markedly increased firing rates. This excitation was of a tonic nature, persisting for a dose-dependent duration in a manner that was not correlated with any of the behavioral effects of the drug. In further analyses, ketamine suppressed the sensory responses of virtually all of the recorded neurons. In particular, low doses of ketamine suppressed "sensorimotor" firing (mainly proprioceptive responses) of neurons in relation to active limb movement. It also suppressed virtually all neuronal sensory responses to the sudden onset of treadmill movement, although the time-course of this effect varied from neuron to neuron. These results reveal two separable effects of ketamine: (a) a strong inhibition of all somatosensory responsiveness in this area and (b) a tonic excitatory influence expressed heterogeneously on a subgroup of neurons. This coexistence of

  8. Serotonin potentiates sympathetic responses evoked by spinal NMDA

    PubMed Central

    Madden, Christopher J; Morrison, Shaun F

    2006-01-01

    In urethane–chloralose anaesthetized, neuromuscularly blocked, ventilated rats, we examined the effects on sympathetic outflow to brown adipose tissue (BAT) of separate and simultaneous spinal microinjections of NMDA and serotonin. Microinjection of NMDA (12 pmol) into the right T4 spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak: +546% of control), BAT thermogenesis (+0.8°C) and heart rate (+53 beats min−1), whereas microinjection of a lower dose of NMDA (1.2 pmol) did not change any of the recorded variables. Microinjection of 5-hydroxytryptamine (5-HT, 2 nmol) into the T4 IML increased BAT SNA (peak: +342% of control) at a long latency (mean onset: 23min). The long latency 5-HT-evoked increase in BAT SNA was prevented by microinjection of methysergide (600 pmol) into the T4 IML. The increases in BAT SNA evoked by T4 IML microinjections of NMDA (12 pmol) were significantly potentiated (two to three times larger than the response to NMDA alone) following T4 IML microinjections of 5-HT (100 pmol to 2 nmol, but not 20 pmol). Also, microinjection of 5-HT (200 pmol) converted the subthreshold dose of NMDA (1.2 pmol) into an effective dose for increasing BAT SNA and heart rate. The 5-HT-mediated potentiation of the increase in BAT SNA evoked by microinjection of NMDA into the T4 IML was reversed by microinjection of methysergide (600 pmol) into the T4 IML. These results demonstrate that BAT SNA and thermogenesis can be driven by activation of spinal excitatory amino acid or 5-HT receptors and that concomitant activation of spinal NMDA and 5-HT receptors can act synergistically to markedly increase BAT SNA and thermogenesis. PMID:16973701

  9. Glutamate and GABA in Vestibulo-Sympathetic Pathway Neurons

    PubMed Central

    Holstein, Gay R.; Friedrich, Victor L. Jr.; Martinelli, Giorgio P.

    2016-01-01

    The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first

  10. Glutamate and GABA in Vestibulo-Sympathetic Pathway Neurons.

    PubMed

    Holstein, Gay R; Friedrich, Victor L; Martinelli, Giorgio P

    2016-01-01

    The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first

  11. Changes in Behavior and Blood Corticosterone Level in Male and Female Rats after Single Administration of Obestatin Fragment 1-4.

    PubMed

    Motorykina, E S; Khirazova, E A; Maslova, M V; Graf, A V; Maklakova, A S; Bayzhumanov, A A; Kurko, O D; Andreeva, L A; Sokolova, N A; Myasoedov, N F; Kamenskii, A A

    2016-06-01

    Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats. PMID:27383154

  12. Significance of Plasma Dopamine β-Hydroxylase Activity as an Index of Sympathetic Neuronal Function

    PubMed Central

    Reid, John L.; Kopin, Irwin J.

    1974-01-01

    Plasma norepinephrine and dopamine β-hydroxylase (EC 1.14.17.1) activity were measured in rats. Adrenergic neuron blockade with bretylium for 4 hr and ganglion blockade with chlorisondamine for 72 hr lowered plasma norepinephrine. Neither treatment altered plasma dopamine β-hydroxylase activity. Phenoxybenzamine for up to 48 hr markedly raised plasma norepinephrine and transiently lowered plasma dopamine β-hydroxylase at 24 hr. Prolonged pharmacological modification of sympathetic nervous activity and plasma norepinephrine were not attended by parallel changes in circulating dopamine β-hydroxylase activity. Plasma dopamine β-hydroxylase activity does not appear to be a sensitive index of prolonged alterations in sympathetic neural activity. Norepinephrine in plasma, however, appears to reflect sensitively and accurately the rate of release of the neurotransmitter. PMID:4530990

  13. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue.

    PubMed

    Binder, Waltraud; Mousa, Shaaban A; Sitte, Nicolle; Kaiser, Myriam; Stein, Christoph; Schäfer, Michael

    2004-07-01

    Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release beta-endorphin, which induces analgesia via activation of peripheral opioid receptors. PMID:15245482

  14. Sympathetic denervation impairs responses of brown adipose tissue to VMH stimulation

    SciTech Connect

    Minokoshi, Y.; Saito, M.; Shimazu, T.

    1986-11-01

    Effects of unilateral surgical denervation of the interscapular brown adipose tissue (IBAT) on its thermogenic and lipogenic responses to electrical stimulation of the ventromedial hypothalamic (VMH) nucleus were studied in anesthetized rats. The rapid rise in IBAT temperature in response to VMH stimulation was greatly suppressed in the denervated IBAT, whereas the temperature response was not impaired in the contralateral innervated IBAT in the same animals. Similarly, the increased rates of conversion of (/sup 14/C) glucose and (/sup 3/H)H/sub 2/O to fatty acids and glyceride glycerol in vivo in IBAT after VMH stimulation were almost completely inhibited by sympathetic denervation. These results indicate clearly that the increases in lipogenic and thermogenic activities in IBAT in response to VMH stimulation are mediated by the sympathetic nerve supply of this tissue.

  15. 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.

  16. Comparing single and repeated dosimetry data for perfluorooctane sulfonate in rats.

    PubMed

    Harris, Leona A; Barton, Hugh A

    2008-10-01

    Perfluorooctane sulfonate (PFOS) is a member of a class of perfluorinated chemicals used in a variety of consumer and industrial applications because of their oleophobic and hydrophobic properties. It has been shown to cause toxicity in adult and developing laboratory animals. Because PFOS has also been shown to be widely distributed throughout the environment, there have been concerns about its potential health risk to humans. Limited pharmacokinetic data for PFOS are available in rodents and humans, while epidemiological studies of workers and extensive toxicity studies in rodents have been performed. The existing pharmacokinetic and toxicity database in rodents can be useful in the cross-species extrapolations needed to evaluate and interpret internal dosimetry in humans. A mathematical model that describes the disposition of PFOS in adult rats following intravenous, oral, and chronic dietary exposures was developed to gain a better understanding of the pharmacokinetics of PFOS and to determine whether single-dose kinetics are predictive of repeated-dose kinetics. In order to characterize existing time-course data, time-dependent and concentration-dependent changes in the pharmacokinetic parameters for urinary and biliary clearance and liver distribution were needed. Whether these time-dependent changes represent inconsistencies across experiments, effects of aging in the rats, or chemically induced changes in pharmacokinetics remains to be determined. PMID:18706985

  17. Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation

    PubMed Central

    Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2014-01-01

    The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement. PMID:25045895

  18. Sympathetic nerve responses to muscle contraction and stretch in ischemic heart failure.

    PubMed

    Koba, Satoshi; Xing, Jihong; Sinoway, Lawrence I; Li, Jianhua

    2008-01-01

    Congestive heart failure (CHF) induces abnormal regulation of peripheral blood flow during exercise. Previous studies have suggested that a reflex from contracting muscle is disordered in this disease. However, there has been very little investigation of the muscle reflex regulating sympathetic outflows in CHF. Myocardial infarction (MI) was induced by the coronary artery ligation in rats. Echocardiography was performed to determine fractional shortening (FS), an index of the left ventricular function. We examined renal and lumbar sympathetic nerve activities (RSNA and LSNA, respectively) during 1-min repetitive (1- to 4-s stimulation to relaxation) contraction or stretch of the triceps surae muscles. During these interventions, the RSNA and LSNA responded synchronously as tension was developed. The RSNA and LSNA responses to contraction were significantly greater in MI rats (n = 13) with FS <30% than in control animals (n = 13) with FS >40% (RSNA: +49 +/- 7 vs. +19 +/- 4 a.u., P < 0.01; LSNA: +28 +/- 7 vs. +8 +/- 2 a.u., P < 0.01) at the same tension development. Stretch also increased the RSNA and LSNA to a larger degree in MI (n = 13) than in control animals (n = 13) (RSNA: +36 +/- 6 vs. +19 +/- 3 a.u., P < 0.05; LSNA: +24 +/- 3 vs. +9 +/- 2 a.u., P < 0.01). The data demonstrate that CHF exaggerates sympathetic nerve responses to muscle contraction as well as stretch. We suggest that muscle afferent-mediated sympathetic outflows contribute to the abnormal regulation of peripheral blood flow seen during exercise in CHF. PMID:17965282

  19. Effects of single-dose and fractionated cranial irradiation on rat brain accumulation of methotrexate

    SciTech Connect

    Kamen, B.A.; Moulder, J.E.; Kun, L.E.; Ring, B.J.; Adams, S.M.; Fish, B.L.; Holcenberg, J.S.

    1984-11-01

    The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same whether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.

  20. Blood Pressure: Return of the Sympathetics?

    PubMed

    Joyner, Michael J; Limberg, Jacqueline K

    2016-01-01

    This brief review highlights new ideas about the role of the sympathetic nervous system in human blood pressure regulation. We emphasize how this role varies with age and sex and use our findings to raise questions about the sympathetic nervous system and hypertension in humans. We also focus on three additional areas, including (1) novel ideas about the carotid body and sympathoexcitation as it relates to hypertension, (2) clinical trials of renal denervation that attempted to treat hypertension by reducing ongoing sympathoexcitation, and (3) new ideas about resistant hypertension and cerebral blood flow. We further highlight that success of device-based therapy to modulate the sympathetic nervous system relies heavily on patient selection. Furthermore, data suggest that the majority of patients respond to anti-hypertensive therapy and the major cause of "resistant" hypertension is poor patient adherence. While the enthusiasm for device therapy or perhaps even "precision medicine" is high, it is likely that by far the most benefit to the most patients will occur via better screening, more aggressive therapy, and the development of strategies that improve patient adherence to medication regimens and lifestyle changes. PMID:26743069

  1. 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

  2. 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

  3. Free mitochondria and synaptosomes from single rat forebrain. A comparison between two known subfractionation techniques.

    PubMed

    Dagani, F; Zanada, F; Marzatico, F; Benzi, G

    1985-08-01

    Two published subcellular subfractionation techniques employing Ficoll-sucrose or sucrose-density gradient centrifugation, respectively, are evaluated for their capacity to yield fractions containing free mitochondria and synaptosomes from a single rat forebrain. The enzymes lactate dehydrogenase, acetylcholinesterase, NAD(P)H-cytochrome c reductase, and citrate synthase, markers of different subcellular components, were used to assess the purity and integrity of the fractions. Judged by the distribution of these specific enzymatic markers, the free mitochondria obtained by the Ficoll-sucrose gradient technique were less contaminated by synaptosomes and had greater biochemical integrity than those obtained by the sucrose-gradient technique. By contrast, the synaptosomes obtained by the Ficoll-sucrose gradient technique resulted in more contamination by microsomes than those prepared in a sucrose gradient. PMID:3925087

  4. Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors

    SciTech Connect

    Huebler, Nicole; Gottschling, Barbara . E-mail: barbara.gottschling@merck.de; Jacobs, Maren; Landenberg, Friedrich von; Hewicker-Trautwein, Marion

    2005-11-01

    Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.

  5. Single trial nicotine conditioned place preference in pre-adolescent male and female rats.

    PubMed

    Edwards, Alexander W; Konz, Nathan; Hirsch, Zahava; Weedon, Jeremy; Dow-Edwards, Diana L

    2014-10-01

    The mean age of first voluntary tobacco inhalation is 12.3 years (DiFranza et al., 2004). 60% of smokers start smoking before the age of 14 and 90% are dependent before reaching the age of 19. Females are typically more sensitive to nicotine than males yet few studies examine the effects of nicotine on the reward systems in pre-adolescent female subjects. This study utilized the single trial conditioned place preference (CPP) test in very young (postnatal day 25-27) rats of both sexes. Latent effects on anxiety and amphetamine response were determined 5 and 7 days following a second nicotine exposure. Results show that 0.05 mg/kg nicotine induced CPP in females following a single trial while both sexes showed CPP following the 0.5 mg/kg dose. Five days later, rats dosed with 0.05 mg/kg show increased time on the open arm of the elevated plus maze, an anxiolytic response. While baseline activity was increased in nicotine-exposed males 7 days following dosing, amphetamine response was not affected by the treatments in either sex. Therefore, our data suggest that young females are more sensitive to nicotine reward than males supporting a heightened sensitivity of the mesolimbic dopamine system in very young females. However, alterations in baseline activity were only seen in males suggesting that different components of the system are affected by nicotine in each sex. An anxiolytic response to nicotine 5 days after dosing may suggest that this very young age group is uniquely affected by this very low nicotine dose. Clearly, nicotine has substantial acute and lasting effects during pre-adolescence at doses substantially lower than seen at older ages as reported by others. These effects, which could potentially result from cigarette or e-cigarette smoking by 11-12 year old children , focus attention on the vulnerability of this age group to nicotine. PMID:25109273

  6. Electroacupuncture at ST25 inhibits jejunal motility: Role of sympathetic pathways and TRPV1

    PubMed Central

    Yu, Zhi; Zhang, Na; Lu, Chun-Xia; Pang, Ting-Ting; Wang, Kai-Yue; Jiang, Jing-Feng; Zhu, Bing; Xu, Bin

    2016-01-01

    AIM: To investigate whether electroacupuncture (EA) at ST25 affects jejunal motility in vivo and if so, whether a sympathetic pathway is involved. METHODS: Jejunal motility was assessed using a manometric balloon placed in the jejunum approximately about 3-5 cm away from the suspensory ligament of the duodenum in anesthetized animals. The effects of EA at ST25 were measured in male Sprague-Dawley rats, some of which were treated with propranolol or clenbuterol (EA intensities: 1, 3, 5, 7, and 9 mA), and in male transient receptor potential vanilloid-1 (TRPV1) (capsaicin receptor) knockout mice (EA intensities: 1, 2, and 4 mA). RESULTS: Anesthetized rats exhibited three types of fasting jejunal motor patterns (types A, B, and C), and only type C rats responded to EA stimulation. In type C rats, EA at ST25 significantly suppressed the motor activity of the jejunum in an intensity-dependent manner. The inhibitory effect of EA was weakened by propranolol (β adrenoceptor antagonist) and disappeared with clenbuterol (β adrenoceptor agonist) induced inhibition of motility, suggesting that the effect of EA on motility is mediated via a sympathetic pathway. Compared with wild-type mice, EA at ST25 was less effective in TRPV1 knockout mice, suggesting that this multi-modal sensor channel participates in the mechanism. CONCLUSION: EA at ST25 was found to inhibit jejunal motility in an intensity-dependent manner, via a mechanism in which sympathetic nerves and TRPV1 receptors play an important role. PMID:26855542

  7. Mild DOCA-salt hypertension: sympathetic system and role of renal nerves.

    PubMed

    Kandlikar, Sachin S; Fink, Gregory D

    2011-05-01

    Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration (day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model. PMID:21357502

  8. Exercise training and α1-adrenoreceptor-mediated sympathetic vasoconstriction in resting and contracting skeletal muscle.

    PubMed

    Just, Timothy P; DeLorey, Darren S

    2016-02-01

    Exercise training (ET) increases sympathetic vasoconstrictor responsiveness and enhances contraction-mediated inhibition of sympathetic vasoconstriction (i.e., sympatholysis) through a nitric oxide (NO)-dependent mechanism. Changes in α2-adrenoreceptor vasoconstriction mediate a portion of these training adaptations, however the contribution of other postsynaptic receptors remains to be determined. Therefore, the purpose of this study was to investigate the effect of ET on α1-adrenoreceptor-mediated vasoconstriction in resting and contracting muscle. It was hypothesized that α1-adrenoreceptor-mediated sympatholysis would be enhanced following ET. Male Sprague Dawley rats were randomized to sedentary (S; n = 12) or heavy-intensity treadmill ET (n = 11) groups. Subsequently, rats were anesthetized and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance (FVC) at rest and during muscle contraction. The percentage change in FVC in response to sympathetic stimulation was measured in control, α1-adrenoreceptor blockade (Prazosin; 20 μg, IV), and combined α1 and NO synthase (NOS) blockade (l-NAME; 5 mg·kg(-1) IV) conditions. Sympathetic vasoconstrictor responsiveness was increased (P < 0.05) in ET compared to S rats at low, but not high (P > 0.05) stimulation frequencies at rest (S: 2 Hz: -25 ± 4%; 5 Hz: -45 ± 5 %; ET: 2 Hz: -35 ± 7%, 5 Hz: -52 ± 7%), whereas sympathetic vasoconstrictor responsiveness was not different (P > 0.05) between groups during contraction (S: 2 Hz: -11 ± 8%; 5 Hz: -26 ± 11%; ET: 2 Hz: -10 ± 7%, 5 Hz: -27 ± 12%). Prazosin blunted (P < 0.05) vasoconstrictor responsiveness in S and ET rats at rest and during contraction, and abolished group differences in vasoconstrictor responsiveness. Subsequent NOS blockade increased vasoconstrictor responses (P < 0.05) in S at rest and during contraction, whereas in ET vasoconstriction was increased (P < 0

  9. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    SciTech Connect

    Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

    1982-01-01

    The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED/sub 50/ dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and ..gamma..-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED/sub 50/ dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair, and even at the highest LET investigated (neon ions in

  10. Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte contractile function in female rats

    PubMed Central

    Kalász, Judit; Tóth, Enikő Pásztor; Bódi, Beáta; Fagyas, Miklós; Tóth, Attila; Pal, Bhattoa Harjit; Vári, Sándor G.; Balog, Marta; Blažetić, Senka; Heffer, Marija; Papp, Zoltán; Borbély, Attila

    2014-01-01

    Aim To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat. Methods Non-ovariectomized (control, n = 8) and ovariectomized (OVX, n = 8) female rats were kept under normal conditions or were exposed to stress (control-S, n = 8 and OVX-S, n = 8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca2+-dependent active force (Factive), Ca2+-independent passive force (Fpassive), and Ca2+-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings. Results Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6 ± 4.8 ng/mL and OVX-S, 21.9 ± 4.0 ng/mL) compared to control (10 ± 2.9 ng/mL) and OVX (2.8 ± 0.5 ng/mL) groups. Factive was higher in the OVX groups (OVX, 25.9 ± 3.4 kN/m2 and OVX-S, 26.3 ± 3.0 kN/m2) than in control groups (control, 16.4 ± 1.2 kN/m2 and control-S, 14.4 ± 0.9 kN/m2). Regarding the potential molecular mechanisms, Factive correlated with MyBP-C phosphorylation, while myofilament Ca2+-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. Fpassive was unaffected by any treatment. Conclusion Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca2+-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca2+-dependent cardiomyocyte contractile

  11. Properties of postganglionic sympathetic neurons with axons in phrenic nerve.

    PubMed

    Bałkowiec, A; Szulczyk, P

    1992-06-01

    The aim of the study was to test the reflex and resting properties of postganglionic sympathetic neurons with axons located in the right phrenic nerve. The experiments have been performed on chloralose-anesthetized cats with both vago-aortic nerves cut. The somata or the postganglionic sympathetic neurons were located in the stellate ganglion. Axons of these neurons passed through the upper and lower phrenic nerve roots and through the phrenic nerve itself. The presence of cardiac and respiratory rhythmicities was detected in the activity of the phrenic postganglionic sympathetic neurons. Hyperventilation, which abolished burst discharges of the phrenic nerve, decreased the sympathetic activity by 14%. Systemic hypoxia (ventilating the animals for 2 min with 8% O2 in N2) increased the sympathetic activity threefold. The results of our experiments suggest that axons of the sympathetic neurons located in the right phrenic nerve could possibly be diaphragmatic muscle vasoconstrictors. PMID:1615229

  12. 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.

  13. Metabolic responses to fasting and refeeding in lean and genetically obese rats.

    PubMed

    Rothwell, N J; Saville, M E; Stock, M J

    1983-05-01

    Injection of norepinephrine (NE) (25 micrograms/100 g body wt) caused a similar rise in metabolic rate in lean and obese (fa/fa) Zucker rats, but 3-day fasting suppressed the response in lean rats and enhanced the rise in obese mutants. Triiodothyronine (T3) injection (10 micrograms/100 g body wt) caused a significantly greater rise in oxygen consumption (Vo2) in obese than lean rats, but the response was attenuated by fasting in all animals. The thermic response to a single meal of either mixed composition, carbohydrate, or protein (40 kJ) was much smaller in obese rats than lean, but the response to the mixed nutrient meal was similar for all rats after a 3-day fast. Refeeding 3-day fasted lean rats with a single carbohydrate meal (40 kJ) caused a rise in plasma T3 levels after 3 h and a delayed increase in metabolic rate 24 h later. Injection of NE instead of refeeding caused a similar delayed rise in metabolic rate. Carbohydrate refeeding had no effect on plasma T3 levels or oxygen consumption in 3-day fasted obese Zuckers, but injection of NE did produce a significant increase in metabolic rate after 24 h. Refeeding 3-day fasted rats with protein (40 kJ) caused a rise in oxygen consumption 24 h later in lean animals but had no effect in obese animals. The data from lean Zucker rats confirm previous findings in Sprague-Dawley rats and suggest that the thermic response to refeeding involves a complex interaction between the sympathetic nervous system and thyroid hormones. Obese Zuckers responded normally to NE and T3, indicating that their reduced thermogenesis after food may be due to insensitivity to nutrient availability or an inability to activate the sympathetic nervous system. PMID:6846570

  14. Teratogenicity of 2-methoxyethanol applied as a single dermal dose to rats.

    PubMed

    Feuston, M H; Kerstetter, S L; Wilson, P D

    1990-10-01

    2-Methoxyethanol (2-ME) was applied as a single dermal dose on the backs of collared, pregnant Sprague-Dawley rats on Gestation Days (GD) 10, 11, 12, 13, or 14 at doses of 0 and 2000 mg/kg, and at doses of 0, 250, 500, and 1000 mg/kg on GD 12. Except for a transient loss in body weight observed the day after 2-ME administration, no signs of maternal toxicity were observed. On GD 20, dams were necropsied and the fetuses evaluated for normal development. Resorptions were significantly (p less than 0.05) increased in dams exposed to 2-ME on GD 10. Fetal body weights were reduced at dose levels of 1000 and 2000 mg/kg, but statistically significant differences were found only on GD 10 and 12. Significant increases in external, visceral, and skeletal malformations were observed in fetuses exposed to 2-ME at dose levels of 500 mg/kg or greater. Defects of the cardiovascular and urinary systems were the prominent visceral malformations observed. Limb defects (especially those pertaining to the digits) and vertebral column defects (primarily of the tail) were the most frequently observed skeletal defects. At the 2000 mg/kg dose level, 2-ME was teratogenic regardless of the GD of administration. Based on the results of this study, the no observed adverse effect level for developmental toxicity for a single dermal dose of 2-ME applied on GD 12 was determined to be 250 mg/kg. PMID:2258010

  15. Single dose toxicity study of IRDye 800CW in Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Marshall, Milton V.; Draney, Daniel; Sevick-Muraca, Eva M.; Olive, D. Michael

    2010-02-01

    Fluorophore-labeled contrast imaging agents are moving toward clinical use as aids in nodal staging and intraoperative resection of tumors. Near-infrared fluorophores with defined toxicity properties will be needed before these agents can be translated to the clinic. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. We report here the results of a preliminary toxicity study on IRDye 800CW carboxylate in preparation for its use as a labeling moiety for targeted contrast agents. Male and female Sprague Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; indocyanine green was used as a comparative control. Following administration of varying doses of either the dyes or saline, animals were observed for up to fourteen days during which time, hematological, clinical chemistry, enzymological, and histological testing was performed on animal subgroups. Under the conditions tested, a single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5 and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. A dose of 20 mg/kg was identified as the NOAEL (no observed adverse effect level) following IV or ID routes of administration of IRDye 800CW.

  16. Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat

    PubMed Central

    van Bregt, Daniel R.; Thomas, Theresa Currier; Hinzman, Jason M.; Cao, Tuoxin; Liu, Mei; Bing, Guoying; Gerhardt, Greg A.; Pauly, James R.; Lifshitz, Jonathan

    2012-01-01

    Dementia and parkinsonism are late-onset symptoms associated with repetitive head injury, as documented in multiple contact-sport athletes. Clinical symptomatology is the likely phenotype of chronic degeneration and circuit disruption in the substantia nigra (SN). To investigate the initiating neuropathology, we hypothesize that a single diffuse brain injury is sufficient to initiate SN neuropathology including neuronal loss, vascular disruption and microglial activation, contributing to neurodegeneration and altered dopamine regulation. Adult, male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury. Stereological estimates indicated a significant 44% loss of the estimated total neuron number in the SN at 28-days post-injury, without atrophy of neuronal nuclear volumes, including 25% loss of tyrosine hydroxylase positive neurons by 28-days post-injury. Multi-focal vascular compromise occurred 1–2 days post-injury, with ensuing microglial activation (significant 40% increase at 4-days). Neurodegeneration (silver-stain technique) encompassed on average 21% of the SN by 7-days post-injury and increased to 29% by 28-days compared to sham (1%). Whole tissue SN, but not striatum, dopamine metabolism was altered at 28-days post-injury, without appreciable gene or protein changes in dopamine synthesis or regulation elements. Together, single moderate diffuse brain injury resulted in SN neurovascular pathology potentially associated with neuroinflammation or dopamine dysregulation. Compensatory mechanisms may preserve dopamine signaling acutely, but subsequent SN damage with aging or additional injury may expose clinical symptomatology of motor ataxias and dementia. PMID:22178300

  17. Anatomical correlates of recovery in single pellet reaching in spinal cord injured rats.

    PubMed

    Hurd, C; Weishaupt, N; Fouad, K

    2013-09-01

    Modeling spinal cord injury (SCI) in animals is challenging because an appropriate combination of lesion location, lesion severity and behavioral testing is essential to analyze recovery of motor function. For particular tests such as single pellet reaching, the contribution of individual descending tracts to recovery has been investigated using specific tract ablation or graded lesions. However, it has not been established whether single pellet reaching is sufficiently sensitive for assessing the efficacy of treatments for cervical SCI (e.g., one of the currently most successful treatment approaches: rehabilitative training). To address this issue, we trained adult rats in single pellet reaching before and after a cervical (C4) spinal lesion. Animals with lesions of increasing severity were grouped into categories based on damage to anatomical structures such as the corticospinal tract (CST) and the rubrospinal tract (RST), two descending motor tracts that have been implicated in fine motor control of the forelimb. We related lesion extent to spontaneous recovery and plasticity-promoting post injury training and found that reaching performance was not correlated with lesion size or the extent of CST or RST injury. Interestingly, the dorsolateral quadrant (DLQ) lesion category, in which the unilateral dorsal CST and most of the unilateral RST are lesioned, was the only category that showed a clear effect of plasticity-promoting treatment (i.e., training), indicating its usefulness as a lesion model for this testing paradigm. The DLQ lesion likely strikes a balance between tissue sparing and functional impairment and is, therefore, best suited to maximize the potential to observe treatment effects of plasticity-promoting treatments using single pellet reaching. Because of the specific lesion size that is necessary to observe treatment effects, the single pellet skilled reaching task can be considered a stringent behavioral test and therefore may be useful for

  18. Histamine induces oscillations of mitochondrial free Ca2+ concentration in single cultured rat brain astrocytes.

    PubMed Central

    Jou, M J; Peng, T I; Sheu, S S

    1996-01-01

    1. The free Ca2+ concentration of mitochondria ([Ca2+]m) in cultured rat brain astrocytes was measured with a fluorescent Ca2+ indicator, rhod-2, and laser confocal microscopy. 2. Confocal images revealed a rhod-2 distribution that matched mitochondrial localization. 3. Using a Ca2+ ionophore, ionomycin, to clamp the [Ca2+]m from 0 to 100 microM in order to obtain the minimal and maximal fluorescence of rhod-2 in situ, a 3.5 +/- 0.4-fold increase in fluorescence intensity was observed, suggesting that the fluorescence of intramitochondrial rhod-2 was responding in a Ca(2+)-sensitive manner, thereby allowing measurements of [Ca2+]m in single astrocytes. 4. Exposure of fura-2-loaded astrocytes to 100 microM histamine produced a rapid and transient increase in cytosolic Ca2+ concentration ([Ca2+]c) that lasted for several tens of seconds. The spike in [Ca2+]c was frequently followed by variable numbers of repetitive oscillations of Ca2+, which appeared to dampen in amplitude with time. 5. This pattern of histamine-induced [Ca2+]c oscillations was also observed in rhod-2-loaded cells suggesting that [Ca2+]m fluctuated with a similar frequency. 6. The oscillations of [Ca2+]m, but not of [Ca2+]c, were abolished by a proton ionophore, carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), and by Ruthenium Red, a mitochondrial Ca(2+)-uniporter inhibitor. 7. These results suggest that the mitochondrial Ca2+ transport systems in cultured rat brain astrocytes are able to relay receptor-mediated [Ca2+]m oscillations into mitochondria. Images Figure 1 Figure 2 Figure 4 PMID:8961176

  19. Dynamic trajectory of multiple single-unit activity during working memory task in rats

    PubMed Central

    Zhang, Xiaofan; Yi, Hu; Bai, Wenwen; Tian, Xin

    2015-01-01

    Working memory plays an important role in complex cognitive tasks. A popular theoretical view is that transient properties of neuronal dynamics underlie cognitive processing. The question raised here as to how the transient dynamics evolve in working memory. To address this issue, we investigated the multiple single-unit activity dynamics in rat medial prefrontal cortex (mPFC) during a Y-maze working memory task. The approach worked by reconstructing state space from delays of the original single-unit firing rate variables, which were further analyzed using kernel principal component analysis (KPCA). Then the neural trajectories were obtained to visualize the multiple single-unit activity. Furthermore, the maximal Lyapunov exponent (MLE) was calculated to quantitatively evaluate the neural trajectories during the working memory task. The results showed that the neuronal activity produced stable and reproducible neural trajectories in the correct trials while showed irregular trajectories in the incorrect trials, which may establish a link between the neurocognitive process and behavioral performance in working memory. The MLEs significantly increased during working memory in the correctly performed trials, indicating an increased divergence of the neural trajectories. In the incorrect trials, the MLEs were nearly zero and remained unchanged during the task. Taken together, the trial-specific neural trajectory provides an effective way to track the instantaneous state of the neuronal population during the working memory task and offers valuable insights into working memory function. The MLE describes the changes of neural dynamics in working memory and may reflect different neuronal population states in working memory. PMID:26441626

  20. Single whole-body exposure to sarin vapor in rats: Long-term neuronal and behavioral deficits

    SciTech Connect

    Grauer, Ettie Chapman, Shira; Rabinovitz, Ishai; Raveh, Lily; Weissman, Ben-Avi; Kadar, Tamar; Allon, Nahum

    2008-03-01

    Freely moving rats were exposed to sarin vapor (34.2 {+-} 0.8 {mu}g/l) for 10 min. Mortality at 24 h was 35% and toxic sings in the surviving rats ranged from sever (prolonged convulsions) through moderate to almost no overt signs. Some of the surviving rats developed delayed, intermittent convulsions. All rats were evaluated for long-term functional deficits in comparison to air-exposed control rats. Histological analysis revealed typical cell loss at 1 week post inhalation exposure. Neuronal inflammation was demonstrated by a 20-fold increase in prostaglandin (PGE{sub 2}) levels 24 h following exposure that markedly decreased 6 days later. An additional, delayed increase in PGE{sub 2} was detected at 1 month and continued to increase for up to 6 months post exposure. Glial activation following neural damage was demonstrated by an elevated level of peripheral benzodiazepine receptors (PBR) seen in the brain 4 and 6 months after exposure. At the same time muscarinic receptors were unaffected. Six weeks, four and six months post exposure behavioral evaluations were performed. In the open field, sarin-exposed rats showed a significant increase in overall activity with no habituation over days. In a working memory paradigm in the water maze, these same rats showed impaired working and reference memory processes with no recovery. Our data suggest long lasting impairment of brain functions in surviving rats following a single sarin exposure. Animals that seem to fully recover from the exposure, and even animals that initially show no toxicity signs, developed some adverse neural changes with time.

  1. Frequency-Dependent Activation of Glucose Utilization in the Superior Cervical Ganglion by Electrical Stimulation of Cervical Sympathetic Trunk

    NASA Astrophysics Data System (ADS)

    Yarowsky, Paul; Kadekaro, Massako; Sokoloff, Louis

    1983-07-01

    Electrical stimulation of the distal stump of the transected cervical sympathetic trunk produces a frequency-dependent activation of glucose utilization, measured by the deoxy[14C]glucose method, in the superior cervical ganglion of the urethane-anesthetized rat. The frequency dependence falls between 0-15 Hz; at 20 Hz the activation of glucose utilization is no greater than at 15 Hz. Deafferentation of the superior cervical ganglion by transection of the cervical sympathetic trunk does not diminish the rate of glucose utilization in the ganglion in the urethane-anesthetized rat. These results indicate that the rate of energy metabolism in an innervated neural structure is, at least in part, regulated by the impulse frequency of the electrical input to the structure, and this regulation may be an essential component of the mechanism of the coupling of metabolic activity to functional activity in the nervous system.

  2. From one generation to the next: a comprehensive account of sympathetic receptor control in branching arteriolar trees.

    PubMed

    Al-Khazraji, Baraa K; Saleem, Amani; Goldman, Daniel; Jackson, Dwayne N

    2015-07-15

    The effect of the sympathetic nervous system on blood flow distribution within skeletal muscle microvasculature is conditional upon regional activation of receptors for sympathetic neurotransmitters. Previous studies have shown that proximal arterioles are largely governed by adrenergic activation, whereas it is speculated that distal branches are controlled by peptidergic and purinergic activation. However, no study has systematically evaluated the activation of adrenergic, peptidergic and purinergic receptors in continuously branching arteriolar trees of an individual skeletal muscle model. Therefore, in the present study, sympathetic agonists were used to evaluate the constriction responses along first to fifth order arterioles in continuously branching arteriolar trees of a in vivo rat gluteus maximus muscle preparation with respect to specific activation of receptors for sympathetic neurotransmitters (α1R, α2R, NPY1R and P2X1R). Constriction responses were incorporated into a mathematical blood flow model to estimate the total flow, resistance and red blood cell flow heterogeneity within a computationally reconstructed gluteus maximus arteriolar network. For the first time, the effects of activating receptors for sympathetic neurotransmitters on vasoconstrictor responses and the ensuing haemodynamics in continuously branching arteriolar trees of skeletal muscle were characterized, where proximal arterioles responded most to α1R and α2R adrenergic activation, whereas distal arterioles responded most to Y1R and P2X1R activation. Total flow and resistance changed with activation of all receptors, whereas red blood cell flow heterogeneity was largely affected by peptidergic and purinergic activation in distal arterioles. The reported data highlight the functional consequences of topologically-dependent sympathetic control and may serve as novel input parameters in computational modelling of network flow. PMID:25952132

  3. Sympathetic activity–associated periodic repolarization dynamics predict mortality following myocardial infarction

    PubMed Central

    Rizas, Konstantinos D.; Nieminen, Tuomo; Barthel, Petra; Zürn, Christine S.; Kähönen, Mika; Viik, Jari; Lehtimäki, Terho; Nikus, Kjell; Eick, Christian; Greiner, Tim O.; Wendel, Hans P.; Seizer, Peter; Schreieck, Jürgen; Gawaz, Meinrad; Schmidt, Georg; Bauer, Axel

    2014-01-01

    Background. Enhanced sympathetic activity at the ventricular myocardium can destabilize repolarization, increasing the risk of death. Sympathetic activity is known to cluster in low-frequency bursts; therefore, we hypothesized that sympathetic activity induces periodic low-frequency changes of repolarization. We developed a technique to assess the sympathetic effect on repolarization and identified periodic components in the low-frequency spectral range (≤0.1 Hz), which we termed periodic repolarization dynamics (PRD). Methods. We investigated the physiological properties of PRD in multiple experimental studies, including a swine model of steady-state ventilation (n = 7) and human studies involving fixed atrial pacing (n = 10), passive head-up tilt testing (n = 11), low-intensity exercise testing (n = 11), and beta blockade (n = 10). We tested the prognostic power of PRD in 908 survivors of acute myocardial infarction (MI). Finally, we tested the predictive values of PRD and T-wave alternans (TWA) in 2,965 patients undergoing clinically indicated exercise testing. Results. PRD was not related to underlying respiratory activity (P < 0.001) or heart-rate variability (P = 0.002). Furthermore, PRD was enhanced by activation of the sympathetic nervous system, and pharmacological blockade of sympathetic nervous system activity suppressed PRD (P ≤ 0.005 for both). Increased PRD was the strongest single risk predictor of 5-year total mortality (hazard ratio 4.75, 95% CI 2.94–7.66; P < 0.001) after acute MI. In patients undergoing exercise testing, the predictive value of PRD was strong and complementary to that of TWA. Conclusion. We have described and identified low-frequency rhythmic modulations of repolarization that are associated with sympathetic activity. Increased PRD can be used as a predictor of mortality in survivors of acute MI and patients undergoing exercise testing. Trial registration. ClinicalTrials.gov NCT00196274. Funding. This study was funded by

  4. Nitric oxide-mediated central sympathetic excitation promotes CNS and pulmonary O₂ toxicity.

    PubMed

    Demchenko, Ivan T; Moskvin, Alexander N; Krivchenko, Alexander I; Piantadosi, Claude A; Allen, Barry W

    2012-06-01

    In hyperbaric oxygen (HBO(2)) at or above 3 atmospheres absolute (ATA), autonomic pathways link central nervous system (CNS) oxygen toxicity to pulmonary damage, possibly through a paradoxical and poorly characterized relationship between central nitric oxide production and sympathetic outflow. To investigate this possibility, we assessed sympathetic discharges, catecholamine release, cardiopulmonary hemodynamics, and lung damage in rats exposed to oxygen at 5 or 6 ATA. Before HBO(2) exposure, either a selective inhibitor of neuronal nitric oxide synthase (NOS) or a nonselective NOS inhibitor was injected directly into the cerebral ventricles to minimize effects on the lung, heart, and peripheral circulation. Experiments were performed on both anesthetized and conscious rats to differentiate responses to HBO(2) from the effects of anesthesia. EEG spikes, markers of CNS toxicity in anesthetized animals, were approximately four times as likely to develop in control rats than in animals with central NOS inhibition. In inhibitor-treated animals, autonomic discharges, cardiovascular pressures, catecholamine release, and cerebral blood flow all remained below baseline throughout exposure to HBO(2). In control animals, however, initial declines in these parameters were followed by significant increases above their baselines. In awake animals, central NOS inhibition significantly decreased the incidence of clonic-tonic convulsions or delayed their onset, compared with controls. The novel findings of this study are that NO produced by nNOS in the periventricular regions of the brain plays a critical role in the events leading to both CNS toxicity in HBO(2) and to the associated sympathetic hyperactivation involved in pulmonary injury. PMID:22442027

  5. Acute intermittent optogenetic stimulation of nucleus tractus solitarius neurons induces sympathetic long-term facilitation

    PubMed Central

    Yamamoto, Kenta; Lalley, Peter

    2014-01-01

    Acute intermittent hypoxia (AIH) induces sympathetic and phrenic long-term facilitation (LTF), defined as a sustained increase in nerve discharge. We investigated the effects of AIH and acute intermittent optogenetic (AIO) stimulation of neurons labeled with AAV-CaMKIIa, hChR2(H134R), and mCherry in the nucleus of the solitary tract (NTS) of anesthetized, vagotomized, and mechanically ventilated rats. We measured renal sympathetic nerve activity (RSNA), phrenic nerve activity (PNA), power spectral density, and coherence, and we made cross-correlation measurements to determine how AIO stimulation and AIH affected synchronization between PNA and RSNA. Sixty minutes after AIH produced by ventilation with 10% oxygen in balanced nitrogen, RSNA and PNA amplitude increased by 80% and by 130%, respectively (P < 0.01). Sixty minutes after AIO stimulation, RSNA and PNA amplitude increased by 60% and 100%, respectively, (P < 0.01). These results suggest that acute intermittent stimulation of NTS neurons can induce renal sympathetic and phrenic LTF in the absence of hypoxia or chemoreceptor afferent activation. We also found that while acute intermittent optogenetic and hypoxic stimulations increased respiration-related RSNA modulation (P < 0.01), they did not increase synchronization between central respiratory drive and RSNA. We conclude that mechanisms that induce LTF originate within the caudal NTS and extend to other interconnecting neuronal elements of the central nervous cardiorespiratory network. PMID:25519734

  6. Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons.

    PubMed

    Wehner, Amanda B; Abdesselem, Houari; Dickendesher, Travis L; Imai, Fumiyasu; Yoshida, Yutaka; Giger, Roman J; Pierchala, Brian A

    2016-05-01

    During development of the peripheral nervous system, excess neurons are generated, most of which will be lost by programmed cell death due to a limited supply of neurotrophic factors from their targets. Other environmental factors, such as 'competition factors' produced by neurons themselves, and axon guidance molecules have also been implicated in developmental cell death. Semaphorin 3A (Sema3A), in addition to its function as a chemorepulsive guidance cue, can also induce death of sensory neurons in vitro The extent to which Sema3A regulates developmental cell death in vivo, however, is debated. We show that in compartmentalized cultures of rat sympathetic neurons, a Sema3A-initiated apoptosis signal is retrogradely transported from axon terminals to cell bodies to induce cell death. Sema3A-mediated apoptosis utilizes the extrinsic pathway and requires both neuropilin 1 and plexin A3. Sema3A is not retrogradely transported in older, survival factor-independent sympathetic neurons, and is much less effective at inducing apoptosis in these neurons. Importantly, deletion of either neuropilin 1 or plexin A3 significantly reduces developmental cell death in the superior cervical ganglia. Taken together, a Sema3A-initiated apoptotic signaling complex regulates the apoptosis of sympathetic neurons during the period of naturally occurring cell death. PMID:27143756

  7. Dysregulation of Neuronal Ca2+ Channel Linked to Heightened Sympathetic Phenotype in Prohypertensive States

    PubMed Central

    Larsen, Hege E.; Bardsley, Emma N.; Lefkimmiatis, Konstantinos

    2016-01-01

    Hypertension is associated with impaired nitric oxide (NO)–cyclic nucleotide (CN)-coupled intracellular calcium (Ca2+) homeostasis that enhances cardiac sympathetic neurotransmission. Because neuronal membrane Ca2+ currents are reduced by NO-activated S-nitrosylation, we tested whether CNs affect membrane channel conductance directly in neurons isolated from the stellate ganglia of spontaneously hypertensive rats (SHRs) and their normotensive controls. Using voltage-clamp and cAMP–protein kinase A (PKA) FRET sensors, we hypothesized that impaired CN regulation provides a direct link to abnormal signaling of neuronal calcium channels in the SHR and that targeting cGMP can restore the channel phenotype. We found significantly larger whole-cell Ca2+ currents from diseased neurons that were largely mediated by the N-type Ca2+ channel (Cav2.2). Elevating cGMP restored the SHR Ca2+ current to levels seen in normal neurons that were not affected by cGMP. cGMP also decreased cAMP levels and PKA activity in diseased neurons. In contrast, cAMP–PKA activity was increased in normal neurons, suggesting differential switching in phosphodiesterase (PDE) activity. PDE2A inhibition enhanced the Ca2+ current in normal neurons to a conductance similar to that seen in SHR neurons, whereas the inhibitor slightly decreased the current in diseased neurons. Pharmacological evidence supported a switching from cGMP acting via PDE3 in control neurons to PDE2A in SHR neurons in the modulation of the Ca2+ current. Our data suggest that a disturbance in the regulation of PDE-coupled CNs linked to N-type Ca2+ channels is an early hallmark of the prohypertensive phenotype associated with intracellular Ca2+ impairment underpinning sympathetic dysautonomia. SIGNIFICANCE STATEMENT Here, we identify dysregulation of cyclic-nucleotide (CN)-linked neuronal Ca2+ channel activity that could provide the trigger for the enhanced sympathetic neurotransmission observed in the prohypertensive state

  8. 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.

  9. Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver.

    PubMed

    Klieverik, Lars P; Janssen, Sarah F; van Riel, Annelieke; Foppen, Ewout; Bisschop, Peter H; Serlie, Mireille J; Boelen, Anita; Ackermans, Mariëtte T; Sauerwein, Hans P; Fliers, Eric; Kalsbeek, Andries

    2009-04-01

    Thyrotoxicosis increases endogenous glucose production (EGP) and induces hepatic insulin resistance. We have recently shown that these alterations can be modulated by selective hepatic sympathetic and parasympathetic denervation, pointing to neurally mediated effects of thyroid hormone on glucose metabolism. Here, we investigated the effects of central triiodothyronine (T(3)) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T(3) or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T(3) microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T(3) microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T(3) microdialysis in the PVN increased EGP by 11 +/- 4% (P = 0.020), while EGP decreased by 5 +/- 8% (ns) in vehicle-treated rats (T(3) vs. Veh, P = 0.030). Plasma glucose increased by 29 +/- 5% (P = 0.0001) after T(3) microdialysis versus 8 +/- 3% in vehicle-treated rats (T(3) vs. Veh, P = 0.003). Similar effects were observed after i.c.v. T(3) administration. Effects of PVN T(3) microdialysis were independent of plasma T(3), insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T(3) microdialysis on EGP. We conclude that stimulation of T(3)-sensitive neurons in the PVN of euthyroid rats increases EGP via sympathetic projections to the liver, independently of circulating glucoregulatory hormones. This represents a unique central pathway for modulation of hepatic glucose metabolism by thyroid hormone. PMID:19321430

  10. Effect of multilevel laboratory rat caging system on the well-being of the singly-housed Sprague Dawley rat.

    PubMed

    Wheeler, R R; Swan, M P; Hickman, D L

    2015-01-01

    Current regulations emphasize that good husbandry practices allow animals to engage in species appropriate postural adjustments without touching the enclosure walls. This study evaluated the well-being of rats housed in a commercially available multilevel rat caging system, with or without access to the upper level of the caging. The evaluation methodologies included assessment of behavioral observations in the home cage, physiological assessment of metabolism and immune function, and determination of the affective state using a spatial cognitive bias assay. The study determined that rats that were provided access to the full multilevel cage during testing after initial restriction to the lower level of the cage demonstrated behavioral changes consistent with a positive affective state, while those with no changes to their housing situation had no significant differences in their affective states. Rats that were consistently housed with access restricted to the lower level of the cage exhibited a tendency to increased neutrophil:lymphocyte ratios as compared with those provided with access to all levels of the multilevel cage. There were no differences in body weight demonstrated between the experimental groups. Overall use of the cage space, as documented through analysis of behavioral observations in the home cage, demonstrated no significant differences in preferred location in the cage during the light or dark cycles, though rats with access to both levels of the cage were significantly more active during the light cycle. The results of this study suggest that the use of a multilevel caging system may improve the well-being of rats used in research. PMID:25117586

  11. Role of supraspinal vasopressin neurones in the effects of atrial natriuretic peptide on sympathetic nerve activity.

    PubMed

    Yusof, A P M; Yusoff, N H M; Suhaimi, F W; Coote, J H

    2009-06-15

    The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus. PMID:19349212

  12. 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

  13. In vivo genotoxicity study of single-wall carbon nanotubes using comet assay following intratracheal instillation in rats.

    PubMed

    Naya, Masato; Kobayashi, Norihiro; Endoh, Shigehisa; Maru, Junko; Honda, Kazumasa; Ema, Makoto; Tanaka, Jin; Fukumuro, Masahito; Hasegawa, Kazushige; Nakajima, Madoka; Hayashi, Makoto; Nakanishi, Junko

    2012-10-01

    The genotoxicity of single-wall carbon nanotubes (SWCNTs) was evaluated in vivo using the comet assay after intratracheal instillation in rats. The SWCNTs were instilled at a dosage of 0.2 or 1.0mg/kg body weight (single instillation group) and 0.04 or 0.2mg/kg body weight once a week for 5weeks (repeated instillation group). As a negative control, 1% Tween 80 was instilled in a similar manner. As a positive control, ethyl methanesulfonate (EMS) at 500mg/kg was administered once orally 3h prior to dissection. Histopathologically, inflammation in the lung was observed for all the SWCNTs in both single and repeated groups. In the comet assay, there was no increase in% tail DNA in any of the SWCNT-treated groups. In the EMS-treated groups, there was a significant increase in% tail DNA compared with the negative control group. The present study indicated that a single intratracheal instillation of SWCNTs (1.0mg/kg) or repeated intratracheal instillation (0.2mg/kg) once a week for five weeks induced a clear inflammatory response (hemorrhage in the alveolus, infiltration of alveolar macrophages and neutrophiles), but no DNA damage, in the lungs in rats. Under the conditions of the test, SWCNTs were not genotoxic in the comet assay following intratracheal instillation in rats. PMID:22735368

  14. Blood glucose level and lipid profile of alloxan-induced hyperglycemic rats treated with single and combinatorial herbal formulations.

    PubMed

    Ojiako, Okey A; Chikezie, Paul C; Ogbuji, Agomuo C

    2016-04-01

    The current study sought to investigate the capacities of single and combinatorial herbal formulations of leaf extracts of Acanthus montanus, Asystasia gangetica, Emilia coccinea, and Hibiscus rosasinensis to reverse hyperglycemia and dyslipidemia in alloxan-induced diabetic male rats. Phytochemical composition of the herbal extracts, fasting plasma glucose concentration (FPGC), and serum lipid profile (SLP) of the rats were measured by standard methods. The relative abundance of phytochemicals in the four experimental leaf extracts was in the following order: flavonoids > alkaloids > saponins > tannins. Hyperglycemic rats (HyGR) treated with single and combinatorial herbal formulations showed evidence of reduced FPGC compared with the untreated HyGR and were normoglycemic (FPGC < 110.0 mg/dL). Similarly, HyGR treated with single and combinatorial herbal formulations showed evidence of readjustments in their SLPs. Generally, HyGR treated with triple herbal formulations (THfs) exhibited the highest atherogenic index compared with HyGR treated with single herbal formulations (SHfs), double herbal formulations (DHfs), and quadruple herbal formulation (QHf). The display of synergy or antagonism by the composite herbal extracts in ameliorating hyperglycemia and dyslipidemia depended on the type and number of individual herbal extract used in constituting the experimental herbal formulations. Furthermore, the capacities of the herbal formulations (SHfs, DHfs, THfs, and QHf) to exert glycemic control and reverse dyslipidemia did not follow predictable patterns in the animal models. PMID:27114943

  15. Blood glucose level and lipid profile of alloxan-induced hyperglycemic rats treated with single and combinatorial herbal formulations

    PubMed Central

    Ojiako, Okey A.; Chikezie, Paul C.; Ogbuji, Agomuo C.

    2015-01-01

    The current study sought to investigate the capacities of single and combinatorial herbal formulations of leaf extracts of Acanthus montanus, Asystasia gangetica, Emilia coccinea, and Hibiscus rosasinensis to reverse hyperglycemia and dyslipidemia in alloxan-induced diabetic male rats. Phytochemical composition of the herbal extracts, fasting plasma glucose concentration (FPGC), and serum lipid profile (SLP) of the rats were measured by standard methods. The relative abundance of phytochemicals in the four experimental leaf extracts was in the following order: flavonoids > alkaloids > saponins > tannins. Hyperglycemic rats (HyGR) treated with single and combinatorial herbal formulations showed evidence of reduced FPGC compared with the untreated HyGR and were normoglycemic (FPGC < 110.0 mg/dL). Similarly, HyGR treated with single and combinatorial herbal formulations showed evidence of readjustments in their SLPs. Generally, HyGR treated with triple herbal formulations (THfs) exhibited the highest atherogenic index compared with HyGR treated with single herbal formulations (SHfs), double herbal formulations (DHfs), and quadruple herbal formulation (QHf). The display of synergy or antagonism by the composite herbal extracts in ameliorating hyperglycemia and dyslipidemia depended on the type and number of individual herbal extract used in constituting the experimental herbal formulations. Furthermore, the capacities of the herbal formulations (SHfs, DHfs, THfs, and QHf) to exert glycemic control and reverse dyslipidemia did not follow predictable patterns in the animal models. PMID:27114943

  16. [A case of prolonged paroxysmal sympathetic hyperactivity].

    PubMed

    Yamamoto, Akiko; Ide, Shuhei; Iwasaki, Yuji; Kaga, Makiko; Arima, Masataka

    2016-03-01

    We report the case of a 4-year-old girl who presented with paroxysmal sympathetic hyperactivity (PSH), after developing severe hypoxic-ischemic-encephalopathy because of cardiopulmonary arrest. She showed dramatic paroxysmal sympathetic activity with dystonia. She was treated with wide variety of medications against PSH, which were found to be effective in previous studies. Among them, morphine, bromocriptine, propranolol, and clonidine were effective in reducing the frequency of her attacks while gabapentin, baclofen, dantrolene, and benzodiazepine were ineffective. Though the paroxysms decreased markedly after the treatment, they could not be completely controlled beyond 500 days. Following the treatment, levels of plasma catecholamines and their urinary metabolites decreased to normal during inter- paroxysms. However, once a paroxysm had recurred, these levels were again very high. This case study is considered significant for two rea- sons. One is that PSH among children have been rarely reported, and the other is that this case of prolonged PSH delineated the transition of plasma catecholamines during the treatment. The excitatory: inhibitory ratio (EIR) model proposed by Baguley was considered while dis- cussing drug sensitivity in this case. Accumulation of similar case studies will help establish more effective treatment strategies and elucidate the pathophysiology of PSH. PMID:27149743

  17. Sympathetic magic in contamination-related OCD.

    PubMed

    Tolin, David F; Worhunsky, Patrick; Maltby, Nicholas

    2004-06-01

    We examined whether patients with contamination-related obsessive-compulsive disorder (OCD) are characterized by sympathetic magic beliefs (i.e., an irrational understanding of how contagion is transmitted). We asked OCD patients (OCs), non-anxious control participants (NACs), and anxious control participants (ACs) to identify a "contaminated" object and rate its degree of contamination on a 0-100 scale. Next, we touched a clean pencil to the object, and participants rated the degree to which the pencil was contaminated. A second pencil was touched to the first pencil and was then rated. This process was continued for 12 pencils (12 degrees of removal from the original object). The same process was repeated using threat-non-relevant stimuli. Results indicated that for threat-relevant stimuli, OCs seemed to perceive a "chain of contagion" in which successive degrees of removal from the original object were not rated as less contaminated. In contrast, NACs and ACs quickly identified the pencils as not contaminated, suggesting that they recognize the contamination as degrading across objects. This difference was not seen using threat-nonrelevant stimuli. We also found that ratings of looming vulnerability (a belief that the contamination is spreading, approaching, or escalating in threat value) mediated the relationship between diagnostic group and the chain of contagion. We suggest that this process may be consistent with the sympathetic magic and disease-avoidance models of disgust, and that disgust may be a fruitful area for exploration in the study of OCD. PMID:15210379

  18. Time-dependent changes in extracellular glutamate in the rat dorsolateral striatum following a single cocaine injection.

    PubMed

    McKee, B L; Meshul, C K

    2005-01-01

    Acute cocaine administration has been shown to alter dorsal striatal plasticity [Proc Natl Acad Sci USA 87 (1990) 6912; Brain Res Bull 30 (1993) 173] and produce long-term neurochemical changes [Pharmacol Biochem Behav 27 (1987) 533]. To date, the effects of acute cocaine on extracellular glutamate and nerve terminal glutamate immunolabeling in the rat dorsolateral striatum have not been reported. To investigate cocaine-induced changes in extracellular glutamate, in vivo microdialysis was carried out in the dorsolateral striatum of rats 1-14 days after receiving a single injection of either vehicle or 15 mg/kg cocaine. There was an increase in the group injected with cocaine 1 day prior to measuring extracellular glutamate as compared with the control group. The group injected with cocaine 3 days prior to the microdialysis session had decreased extracellular glutamate levels. Furthermore, extracellular glutamate remained attenuated 14 days after acute cocaine treatment. Striatal glutamate decreased in the cocaine-treated rats after calcium removal, suggesting that cocaine-induced changes in extracellular glutamate were partially calcium-dependent. The density of nerve terminal glutamate immunolabeling was measured using immunogold electron microscopy in the contralateral striatum of the same rats that had been acutely treated with cocaine or vehicle. There were no changes in the density of glutamate immunolabeling within identified nerve terminals making an asymmetrical (excitatory) synaptic contact 1, 2, 3, or 14 days after acute cocaine exposure as compared with the control groups. Hence, these alterations in extracellular glutamate did not result from changes in glutamate immunolabeling within the synaptic vesicle pool. In addition, no changes in glutamate immunolabeling were found in rats that received cocaine 2 h previously or were withdrawn after 1 week of cocaine administration. The results demonstrate that a single injection of cocaine produces biphasic

  19. Pharmacokinetics of A40926 in rats after single intravenous and subcutaneous doses.

    PubMed Central

    Bernareggi, A; Danese, A; Cavenaghi, L

    1988-01-01

    A40926 is a new glycopeptide antibiotic with unique activity against Neisseria gonorrhoeae and high and prolonged levels in mouse blood (B. P. Goldstein, E. Selva, L. Gastaldo, M. Berti, R. Pallanza, F. Ripamonti, P. Ferrari, M. Denaro, V. Arioli, and G. Cassani, Antimicrob. Agents Chemother., 31:1961-1966, 1987). We studied the pharmacokinetics of A40926 in rats after single intravenous and subcutaneous 10-mg/kg (body weight) doses. Concentrations in plasma and urine were determined by microbiological assay. After intravenous administration, high concentrations of A40926, ranging from 132 mg/liter at 3 min to 0.7 mg/liter at 96 h, were found in plasma. Concentrations declined with a three-exponential decay correlated with a prolonged, biphasic distribution and a slow elimination (terminal half-life, 61.22 h). After completion of the distribution, the compound was widely distributed to the extravascular space. The rate-limiting step in the elimination of A40926 from the body appears to be the slow return from the deep compartment into the central one. A40926 was rapidly absorbed from the injection site after subcutaneous administration, and its availability was close to 90%. The percentage of the dose excreted in urine in 120 h was 35.9%. PMID:3364946

  20. Single-channel properties of a rat brain endoplasmic reticulum anion channel.

    PubMed Central

    Clark, A G; Murray, D; Ashley, R H

    1997-01-01

    Many intracellular membranes contain ion channels, although their physiological roles are often poorly understood. In this study we incorporated single anion channels colocalized with rat brain endoplasmic reticulum (ER) ryanodine-sensitive Ca(2+)-release channels into planar lipid bilayers. The channels opened in bursts, with more activity at negative (cytoplasm-ER lumen) membrane potentials, and they occupied four open conductance levels with frequencies well described by the binomial equation. The probability of a protomer being open decreased from approximately 0.7 at -40 mV to approximately 0.2 at +40 mV, and the channels selected between different anions in the order PSCN > PNO3 > PBr > PCl > PF. They were also permeant to cations, including the large cation Tris+ (PTris/PCl = 0.16). Their conductance saturated at 170 pS in choline Cl. The channels were inactivated by 15 microM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and blocked with low affinity (KD of 1-100 microM) by anthracene-9-carboxylic acid, ethacrynic acid, frusemide (furosemide), HEPES, the indanyloxyacetic acid derivative IAA-94, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), and Zn2+. Unlike protein translocation pores, the channels were unaffected by high salt concentrations or puromycin. They may regulate ER Ca2+ release, or be channel components en route to their final cellular destinations. Alternatively, they may contribute to the fusion machinery involved in intracellular membrane trafficking. PMID:9199781

  1. Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain

    PubMed Central

    Granholm, L; Roman, E; Nylander, I

    2015-01-01

    BACKGROUND AND PURPOSE A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats. EXPERIMENTAL APPROACH Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg6Phe7 (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA. KEY RESULTS Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B. CONCLUSIONS AND IMPLICATIONS Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http

  2. 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

  3. 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.

  4. 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

  5. Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

    PubMed Central

    Colombari, Débora S A; Colombari, Eduardo; Freiria-Oliveira, Andre H; Antunes, Vagner R; Yao, Song T; Hindmarch, Charles; Ferguson, Alastair V; Fry, Mark; Murphy, David; Paton, Julian F R

    2011-01-01

    Abstract We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2–3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT1 receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t)SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla–spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e.g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EH rats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration. PMID:21708906

  6. Resonant oscillation modes of sympathetically cooled ions in a radio-frequency trap

    SciTech Connect

    Hasegawa, Taro; Shimizu, Tadao

    2002-12-01

    Sympathetic cooling of Ca{sup +}, Zn{sup +}, Sr{sup +}, Ba{sup +}, and Yb{sup +} as guest ions with laser-cooled {sup 24}Mg{sup +} as host ions in a rf ion trap is carried out, and resonant frequencies of their motion in the trap potential are measured. Various oscillation modes of the sympathetically cooled ions are observed. The resonant frequency of the oscillation mode is different from the frequency of either the collective oscillation frequency of the trapped ions or the oscillation frequency of each ion without host ions. This difference is well explained by a theoretical model in which coupled equations of motion of the host ion cloud with a single guest ion are considered.

  7. LONG TERM RESPONSE OF RATS TO SINGLE INTRATRACHEAL EXPOSURE OF LIBBY AMPHIBOLE (LA) OR AMOSITE

    EPA Science Inventory

    In former mine workers of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, we investigated long term effects of Libby amphibole (LA) exposure in a rat model. Rat respirable ...

  8. Relaxin in paraventricular nucleus contributes to sympathetic overdrive and hypertension via PI3K-Akt pathway.

    PubMed

    Sun, Hai-Jian; Chen, Dan; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Chen, Qi; Li, Yue-Hua; Gao, Xing-Ya; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-04-01

    Relaxin is recognized as an ovarian polypeptide hormone. Abundant relaxin binding sites are observed in hypothalamic paraventricular nucleus (PVN). This study was conducted to determine the roles and underlying mechanisms of relaxin in the PVN in sympathetic activation and hypertension in spontaneously hypertensive rats (SHR). Experiments were performed in normotensive Wistar-Kyoto rats (WKY) and SHR. Relaxin and its RXFP1 receptors in PVN were up-regulated in SHR. Relaxin-positive neurons existed in both parvocellular and magnocellular parts of the PVN. Presympathetic neurons and AVP neurons in the PVN expressed RXFP1, but not relaxin. Bilateral PVN microinjection of human relaxin-2 increased but anti-relaxin IgG reduced renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), plasma norepinephrine (NE) and arginine vasopressin (AVP) levels in SHR. The effects of relaxin-2 on RSNA and MAP were abolished by intravenous infusion of ganglionic blocker hexamethonium, and attenuated by AVP V1 receptor antagonist AAVP. Akt phosphorylation was enhanced in SHR, and relaxin-2 stimulated Akt phosphorylation and p85α subunit of PI3K expression. PI3K inhibitor LY294002 or Akt inhibitor MK-2206 abolished the effects of relaxin-2 on the RSNA, MAP and plasma NE, and attenuated the relaxin-2-induced AVP secretion. STAT5a and polymerase II (Pol II) binding to relaxin-promoter were significantly increased in SHR. Chronic PVN infusion of relaxin-2 with osmotic pumps in normal rats induced sympathetic activation, AVP secretion and hypertension accompanied with cardiovascular remodeling. Relaxin in the PVN contributes to sympathetic overdrive and hypertension via PI3K-Akt pathway. PMID:26746861

  9. 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

  10. Radiotracers for Cardiac Sympathetic Innervation: Transport Kinetics and Binding Affinities for the Human Norepinephrine Transporter

    PubMed Central

    Raffel, David M.; Chen, Wei; Jung, Yong-Woon; Jang, Keun Sam; Gu, Guie; Cozzi, Nicholas V.

    2013-01-01

    Introduction Most radiotracers for imaging of cardiac sympathetic innervation are substrates of the norepinephrine transporter (NET). The goal of this study was to characterize the NET transport kinetics and binding affinities of several sympathetic nerve radiotracers, including [11C]-(−)-meta-hydroxyephedrine, [11C]-(−)-epinephrine, and a series of [11C]-labeled phenethylguanidines under development in our laboratory. For comparison, the NET transport kinetics and binding affinities of some [3H]-labeled biogenic amines were also determined. Methods Transport kinetics studies were performed using rat C6 glioma cells stably transfected with the human norepinephrine transporter (C6-hNET cells). For each radiolabeled NET substrate, saturation transport assays with C6-hNET cells measured the Michaelis-Menten transport constants Km and Vmax for NET transport. Competitive inhibition binding assays with homogenized C6-hNET cells and [3H]mazindol provided estimates of binding affinities (KI) for NET. Results Km, Vmax and KI values were determined for each NET substrate with a high degree of reproducibility. Interestingly, C6-hNET transport rates for ‘tracer concentrations’ of substrate, given by the ratio Vmax/Km, were found to be highly correlated with neuronal transport rates measured previously in isolated rat hearts (r2 = 0.96). This suggests that the transport constants Km and Vmax measured using the C6-hNET cells accurately reflect in vivo transport kinetics. Conclusion The results of these studies show how structural changes in NET substrates influence NET binding and transport constants, providing valuable insights that can be used in the design of new tracers with more optimal kinetics for quantifying regional sympathetic nerve density. PMID:23306137

  11. Sympathetic cooling of nanospheres with cold atoms

    NASA Astrophysics Data System (ADS)

    Montoya, Cris; Witherspoon, Apryl; Ranjit, Gambhir; Casey, Kirsten; Kitching, John; Geraci, Andrew

    2016-05-01

    Ground state cooling of mesoscopic mechanical structures could enable new hybrid quantum systems where mechanical oscillators act as transducers. Such systems could provide coupling between photons, spins and charges via phonons. It has recently been shown theoretically that optically trapped dielectric nanospheres could reach the ground state via sympathetic cooling with trapped cold atoms. This technique can be beneficial in cases where cryogenic operation of the oscillator is not practical. We describe experimental advances towards coupling an optically levitated dielectric nanosphere to a gas of cold Rubidium atoms. The sphere and the cold atoms are in separate vacuum chambers and are coupled using a one-dimensional optical lattice. This work is partially supported by NSF, Grant Nos. PHY-1205994,PHY-1506431.

  12. Sympathetic cooling of {sup 6}Li atoms

    SciTech Connect

    van Abeelen, F.A.; Verhaar, B.J.; Moerdijk, A.J.

    1997-06-01

    We use recently measured cold photoassociation and two-photon data to extract the singlet and triplet accumulated radial phases of interacting ground-state lithium atoms. Using the resulting values we predict scattering lengths, Feshbach resonances, and exchange decay rates for cold collisions between {sup 7}Li and {sup 6}Li atoms that are of interest for the possibility of sympathetic cooling of {sup 6}Li and for the coexistence of the bosonic and fermionic quantum-degenerate phases of {sup 7}Li and {sup 6}Li. In addition, we calculate scattering lengths and exchange decay rates for cold collisions between identical lithium isotopes in different hyperfine states. These quantities are used to examine the possibilities of coexisting {sup 7}Li Bose condensates and of evaporatively cooling coexisting {sup 6}Li subsystems. {copyright} {ital 1997} {ital The American Physical Society}

  13. Antihypertensive drugs and the sympathetic nervous system.

    PubMed

    Del Colle, Sara; Morello, Fulvio; Rabbia, Franco; Milan, Alberto; Naso, Diego; Puglisi, Elisabetta; Mulatero, Paolo; Veglio, Franco

    2007-11-01

    Hypertension has been associated with several modifications in the function and regulation of the sympathetic nervous system (SNS). Although it is unclear whether this dysfunction is primary or secondary to the development of hypertension, these alterations are considered to play an important role in the evolution, maintenance, and development of hypertension and its target organ damage. Several pharmacological antihypertensive classes are currently available. The main drugs that have been clearly shown to affect SNS function are beta-blockers, alpha-blockers, and centrally acting drugs. On the contrary, the effects of ACE inhibitors (ACE-Is), AT1 receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics on SNS function remain controversial. These properties are pharmacologically and pathophysiologically relevant and should be considered in the choice of antihypertensive treatments and combination therapies in order to achieve, beyond optimal blood pressure control, a normalization of SNS physiology and the most effective prevention of target organ damage. PMID:18030057

  14. Spontaneous Changes in Taste Sensitivity of Single Units Recorded over Consecutive Days in the Brainstem of the Awake Rat

    PubMed Central

    Sammons, Joshua D.; Weiss, Michael S.; Escanilla, Olga D.; Fooden, Andrew F.; Victor, Jonathan D.

    2016-01-01

    A neuron’s sensitivity profile is fundamental to functional classification of cell types, and underlies theories of sensory coding. Here we show that gustatory neurons in the nucleus of the solitary tract (NTS) and parabrachial nucleus of the pons (PbN) of awake rats spontaneously change their tuning properties across days. Rats were surgically implanted with a chronic microwire assembly into the NTS or PbN. Following recovery, water-deprived rats had free access to a lick spout that delivered taste stimuli while cellular activity was recorded. In 12 rats for the NTS and 8 rats for the PbN, single units could be isolated at the same electrode on consecutive days (NTS, 14 units for 2–5 consecutive days, median = 2 days; PbN, 23 units for 2–7 days, median = 2.5 days). Waveforms were highly similar (waveform template correlation > 0.99) across days in 13 units in NTS and 13 units in PbN. This degree of similarity was rare (0.3% of pairs in NTS, 1.5% of pairs in PbN) when the waveforms were from presumed-different neurons (units recorded on nonconsecutive days with at least one intervening day in which there were no spikes, or from different wires or rats). Analyses of multi-day recordings that met this criterion for “same unit” showed that responses to taste stimuli appeared, disappeared, or shifted in magnitude across days, resulting in changes in tuning. These data imply, generally, that frameworks for cell classification and, specifically, that theories of taste coding, need to consider plasticity of response profiles. PMID:27479490

  15. Spontaneous Changes in Taste Sensitivity of Single Units Recorded over Consecutive Days in the Brainstem of the Awake Rat.

    PubMed

    Sammons, Joshua D; Weiss, Michael S; Escanilla, Olga D; Fooden, Andrew F; Victor, Jonathan D; Di Lorenzo, Patricia M

    2016-01-01

    A neuron's sensitivity profile is fundamental to functional classification of cell types, and underlies theories of sensory coding. Here we show that gustatory neurons in the nucleus of the solitary tract (NTS) and parabrachial nucleus of the pons (PbN) of awake rats spontaneously change their tuning properties across days. Rats were surgically implanted with a chronic microwire assembly into the NTS or PbN. Following recovery, water-deprived rats had free access to a lick spout that delivered taste stimuli while cellular activity was recorded. In 12 rats for the NTS and 8 rats for the PbN, single units could be isolated at the same electrode on consecutive days (NTS, 14 units for 2-5 consecutive days, median = 2 days; PbN, 23 units for 2-7 days, median = 2.5 days). Waveforms were highly similar (waveform template correlation > 0.99) across days in 13 units in NTS and 13 units in PbN. This degree of similarity was rare (0.3% of pairs in NTS, 1.5% of pairs in PbN) when the waveforms were from presumed-different neurons (units recorded on nonconsecutive days with at least one intervening day in which there were no spikes, or from different wires or rats). Analyses of multi-day recordings that met this criterion for "same unit" showed that responses to taste stimuli appeared, disappeared, or shifted in magnitude across days, resulting in changes in tuning. These data imply, generally, that frameworks for cell classification and, specifically, that theories of taste coding, need to consider plasticity of response profiles. PMID:27479490

  16. pH buffering of single rat skeletal muscle fibers in the in vivo environment.

    PubMed

    Tanaka, Yoshinori; Inagaki, Tadakatsu; Poole, David C; Kano, Yutaka

    2016-05-15

    Homeostasis of intracellular pH (pHi) has a crucial role for the maintenance of cellular function. Several membrane transporters such as lactate/H(+) cotransporter (MCT), Na(+)/H(+) exchange transporter (NHE), and Na(+)/HCO3 (-) cotransporter (NBC) are thought to contribute to pHi regulation. However, the relative importance of each of these membrane transporters to the in vivo recovery from the low pHi condition is unknown. Using an in vivo bioimaging model, we pharmacologically inhibited each transporter separately and all transporters together and then evaluated the pHi recovery profiles following imposition of a discrete H(+) challenge loaded into single muscle fibers by microinjection. The intact spinotrapezius muscle of adult male Wistar rats (n = 72) was exteriorized and loaded with the fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymethyl ester (10 μM). A single muscle fiber was then loaded with low-pH solution [piperazine-N,N'-bis(2-ethanesulfonic acid) buffer, pH 6.5, ∼2.33 × 10(-3) μl] by microinjection over 3 s. The rats were divided into groups for the following treatments: 1) no inhibitor (CONT), 2) MCT inhibition (by α-Cyano-4-hydroxyciannamic acid; 4 mM), 3) NHE inhibition (by ethylisopropyl amiloride; 0.5 mM), 4) NBC inhibition (by DIDS; 1 mM), and 5) MCT, NHE, and NBC inhibition (All blockade). The fluorescence ratio (F500 nm/F445 nm) was determined from images captured during 1 min (60 images/min) and at 5, 10, 15, and 20 min after injection. The pHi at 1-2 s after injection significantly decreased from resting pHi (ΔpHi = -0.73 ± 0.03) in CONT. The recovery response profile was biphasic, with an initial rapid and close-to-exponential pHi increase (time constant, τ: 60.0 ± 7.9 s). This initial rapid profile was not affected by any pharmacological blockade but was significantly delayed by carbonic anhydrase inhibition. In contrast, the secondary, more gradual, return toward baseline that restored CONT pHi to

  17. Renal sympathetic nerve ablation for treatment-resistant hypertension

    PubMed Central

    Krum, Henry; Schlaich, Markus; Sobotka, Paul

    2013-01-01

    Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

  18. 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

  19. Sympathetically mediated hypertension in autonomic failure

    NASA Technical Reports Server (NTRS)

    Shannon, J. R.; Jordan, J.; Diedrich, A.; Pohar, B.; Black, B. K.; Robertson, D.; Biaggioni, I.; Roberton, D. (Principal Investigator)

    2000-01-01

    BACKGROUND: Approximately 50% of patients with primary autonomic failure have supine hypertension. We investigated whether this supine hypertension could be driven by residual sympathetic activity. METHODS AND RESULTS: In patients with multiple system atrophy (MSA) or pure autonomic failure (PAF), we studied the effect of oral yohimbine on seated systolic blood pressure (SBP), the effect of ganglionic blockade (with trimethaphan) on supine SBP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phentolamine) on supine SBP. The SBP response to yohimbine was greater in patients with MSA than in those with PAF (area under the curve, 2248+/-543 versus 467+/-209 mm Hg. min; P=0.022). MSA patients with a higher supine SBP had a greater response than those with a lower supine SBP (3874+/-809 versus 785+/-189 mm Hg. min; P=0. 0017); this relationship was not seen in PAF patients. MSA patients had a marked depressor response to low infusion rates of trimethaphan; the response in PAF patients was more variable. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. At 1 mg/min, trimethaphan decreased supine SBP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respectively (P<0.0001). Cardiac index and total peripheral resistance decreased in MSA patients by 33.4+/-5.8% and 40.7+/-9.5%, respectively (P=0. 0015). Patients having a depressor response to trimethaphan also had a depressor response to phentolamine. In MSA patients, the pressor response to yohimbine and the decrease in SBP with 1 mg/min trimethaphan were correlated (r=0.98; P=0.001). CONCLUSIONS: Residual sympathetic activity drives supine hypertension in MSA. It contributes to, but does not completely explain, supine hypertension in PAF.

  20. Chain Reconnections Observed in Sympathetic Eruptions

    NASA Astrophysics Data System (ADS)

    Joshi, Navin Chandra; Schmieder, Brigitte; Magara, Tetsuya; Guo, Yang; Aulanier, Guillaume

    2016-04-01

    The nature of various plausible causal links between sympathetic events is still a controversial issue. In this work, we present multiwavelength observations of sympathetic eruptions, associated flares, and coronal mass ejections (CMEs) occurring on 2013 November 17 in two close active regions. Two filaments, i.e., F1 and F2, are observed in between the active regions. Successive magnetic reconnections, caused for different reasons (flux cancellation, shear, and expansion) have been identified during the whole event. The first reconnection occurred during the first eruption via flux cancellation between the sheared arcades overlying filament F2, creating a flux rope and leading to the first double-ribbon solar flare. During this phase, we observed the eruption of overlying arcades and coronal loops, which leads to the first CME. The second reconnection is believed to occur between the expanding flux rope of F2 and the overlying arcades of filament F1. We suggest that this reconnection destabilized the equilibrium of filament F1, which further facilitated its eruption. The third stage of reconnection occurred in the wake of the erupting filament F1 between the legs of the overlying arcades. This may create a flux rope and the second double-ribbon flare and a second CME. The fourth reconnection was between the expanding arcades of the erupting filament F1 and the nearby ambient field, which produced the bi-directional plasma flows both upward and downward. Observations and a nonlinear force-free field extrapolation confirm the possibility of reconnection and the causal link between the magnetic systems.

  1. 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.

  2. [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

  3. Measurement of Na-K-ATPase-mediated rubidium influx in single segments of rat nephron

    SciTech Connect

    Cheval, L.; Doucet, A. )

    1990-07-01

    To determine the functioning rate of Na-K-ATPase in the rat nephron, a micromethod was developed to measure the rate of rubidium uptake in single nephron segments microdissected from collagenase-treated kidneys. Because the hydrolytic activity of Na-K-ATPase displayed the same apparent affinity for K and Rb ions, whereas the Vmax elicited by K was higher than that in the presence of Rb, experiments were performed in the presence of cold Rb plus 86Rb. Before the assay, tubules were preincubated for 10 min at 37 degrees C to restore the normal transmembrane cation gradients. 86Rb uptake was measured after washing out extracellular cations by rinsing the tubules in ice-cold choline chloride solution containing Ba2+. Rb uptake increased quasi-linearly as a function of incubation time up to 30 s in the thick ascending limb, 1 min in the proximal convoluted tubule, and 5 min in the collecting tubule, and reached an equilibrium after 5-30 min. The initial rates of Rb uptake increased in a saturable fashion as Rb concentration in the medium rose from 0.25 to 5 mM. In medullary thick ascending limb, the initial rate of Rb uptake was inhibited by greater than 90% by 2.5 mM ouabain and by 10(-5) M of the metabolic inhibitor carbonyl cyanide trifluoromethoxyphenylhydrazone. Correlation of Na-K-ATPase hydrolytic activity at Vmax and initial rates of ouabain-sensitive Rb uptake in the successive segments of nephron indicates that in intact cells the pump works at approximately 20-30% of its Vmax. Increasing intracellular Na concentration by tubule preincubation in a Rb- and K-free medium increased the initial rates of Rb intake up to the Vmax of the hydrolytic activity of the pump.

  4. A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats

    PubMed Central

    Springborg, Jacob Bertram; Ma, XiaoDong; Rochat, Per; Knudsen, Gitte Moos; Amtorp, Ole; Paulson, Olaf B; Juhler, Marianne; Olsen, Niels Vidiendal

    2002-01-01

    Systemic administration of recombinant erythropoietin (EPO) has been demonstrated to mediate neuroprotection. This effect of EPO may in part rely on a beneficial effect on cerebrovascular dysfunction leading to ischaemic neuronal damage. We investigated the in vivo effects of subcutaneously administered recombinant EPO on impaired cerebral blood flow (CBF) autoregulation after experimental subarachnoid haemorrhage (SAH).Four groups of male Sprague-Dawley rats were studied: group A, sham operation plus vehicle; group B, sham operation plus EPO; group C, SAH plus vehicle; group D, SAH plus EPO. SAH was induced by injection of 0.07 ml of autologous blood into the cisterna magna. EPO (400 iu kg−1 s.c.) or vehicle was given immediately after the subarachnoid injection of blood or saline. Forty-eight hours after the induction of SAH, CBF autoregulatory function was evaluated using the intracarotid 133Xe method.CBF autoregulation was preserved in both sham-operated groups (lower limits of mean arterial blood pressure: 91±3 and 98±3 mmHg in groups A and B, respectively). In the vehicle treated SAH-group, autoregulation was abolished and the relationship between CBF and blood pressure was best described by a single linear regression line. A subcutaneous injection of EPO given immediately after the induction of SAH normalized autoregulation of CBF (lower limit in group D: 93±4 mmHg, NS compared with groups A and B).Early activation of endothelial EPO receptors may represent a potential therapeutic strategy in the treatment of cerebrovascular perturbations after SAH. PMID:11834631

  5. [Intestinal absorption of aloe-emodin using single-passintestinal perfusion method in rat].

    PubMed

    Wang, Jinrong; Wang, Ping; Yang, Yongmao; Meng, Xianli; Zhang, Yan

    2011-09-01

    The intestinal absorption of aloe-emodin was investigated using the single pass intestinal perfusion (SPIP) technique in S/D rats. SPIP was performed in each isolated segment of the intestine (i.e., duodenum, jejunum, ileum and colon) and the different concentrations inhibitor group of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) with the concentrations of aloe-emodin (0.238 mg x L(-1)) at a flow rate of 0.28 mL x min(-1). The effective absorption rate constant (Ka) and apparent absorption coefficient (Papp) of aloe-emodin for each segment were determined before and after treated with different concentrations of inhibitors of P-gp and MRP2 respectively. Aloe-emodin exhibits a high intestinal permeability except the the ileum, indicative that the compounds are well absorbed. Decreases of Ka and Papp values in the duodenum, jejunum, colon and ileum, furthermore, the duodenum has significant increased compared with the ileum, there are have no significant difference in other isolated region of the intestine. Compared with the group which have no inhibitor of P-gp, the Ka and Papp were significantly increased in inhibitor of P-gp groups. Compared with the group of no inhibitor of MRP2, the Ka and Papp were significantly increased in inhibitor of MRP2 groups with the highest and the middle concentration. The results suggested that the inhibitors of P-gp and MRP2 all can promote the intestinal absorption of aloe-emodin. PMID:22121810

  6. Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat.

    PubMed

    Cook, Thomas J; Shenoy, Smriti S

    2003-03-01

    The intestinal transport of chlorpyrifos (CPF), an organothiophosphate pesticide, was investigated using the single-pass intestinal perfusion (SPIP) technique in male, Sprague-Dawley rats. SPIP was performed in each isolated region of the small intestine (i.e. duodenum, jejunum and ileum) with three concentrations of CPF (0.1, 2.0 and 10 microM) at a flow rate of 0.25 ml/min. Preliminary binding and stability studies were conducted to ensure that the loss of CPF in the SPIP study can be attributed to intestinal absorption. The effective permeability (P(eff)) of CPF was determined for each segment and concentration. CPF exhibits a high intestinal permeability over the length of the small intestine indicative of compounds that are well absorbed. Decreases in permeability values at the highest CPF concentration studied in the duodenum and ileum suggest a saturable transport process. Based on these results, passive, transcellular diffusion dominates the intestinal transport mechanism of CPF, with a saturable transport process evident in the duodenum and ileum. The P(eff) of CPF is in the range of drugs with high intestinal permeability and high fraction of dose absorbed indicating that CPF readily crosses the intestine. The dependence of CPF's P(eff) on concentration in the duodenum and ileum suggests that CPF is transported by a combination of mechanisms across the intestine. Using established relationships, the human fraction dose absorbed for CPF was estimated to be >99%. The permeability values obtained from this study may be useful in models of exposure assessment. PMID:12499115

  7. Regional blood flow in rats after a single low-protein, high-carbohydrate test meal.

    PubMed

    Glick, Z; Wickler, S J; Stern, J S; Horwitz, B A

    1984-07-01

    It was previously observed that a single low-protein, high-carbohydrate test meal results in increased in vitro thermic activity of brown adipose tissue. In the present study, we have examined whether such a meal increases the in vivo thermic activity, estimated from measurement of the rate of blood flow. With radioactively labeled microspheres, blood flows into brown fat and several other tissues were determined in meal-deprived (n = 11) and meal-fed (n = 11) rats. The microspheres were injected into the heart of anesthetized animals about 2-2.5 h after the test meal, one injection in the resting state and one during maximal norepinephrine stimulation. In the resting state, blood flow per gram tissue more than doubled in the brown fat (P less than 0.05) and was increased more than 50% in the heart (P less than 0.01) of the fed group. Blood flows into liver and retroperitoneal white fat were reduced by 40 (P less than 0.01) and 30%, respectively, in the fed group. During norepinephrine infusion, significant meal-associated increases in blood flow were evident only in brown fat (P less than 0.05) and the soleus muscle (P less than 0.05), whereas a significant decrease was observed in the liver (P less than 0.05). No statistically significant meal-associated changes in norepinephrine-stimulated blood flow were found in the other tissues examined (i.e., heart, gastrocnemius, and diaphragm muscles, kidneys, white fat, spleen, and adrenals). Our in vivo data thus support the view that brown fat plays a role in the thermic effect of a meal. PMID:6742226

  8. Clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery.

    PubMed

    Adamson, R H; Ly, J C; Fernandez-Miyakawa, M; Ochi, S; Sakurai, J; Uzal, F; Curry, F E

    2005-08-01

    Epsilon-toxin, the primary virulence factor of Clostridium perfringens type D, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. It is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endothelial damage and edema. Here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properties of the in situ vascular wall during exposure to toxin. We determined the hydraulic conductivity (L(p)) of microvessels as a measure of the response to epsilon-toxin. We found that microvessels were highly sensitive to toxin. At 10 microg ml(-1) the L(p) increased irreversibly to more than 15 times the control value by 10 min. At 0.3 microg ml(-1) no increase in L(p) was observed for up to 90 min. The toxin-induced increase in L(p) was consistent with changes in ultrastructure of microvessels exposed to the toxin. Those microvessels exhibited gaps either between or through endothelial cells where perfusate had direct access to the basement membrane. Many endothelial cells appeared necrotic, highly attenuated, and with dense cytoplasm. We showed that epsilon-toxin, in a time- and dose-dependent manner, rapidly and irreversibly compromised the barrier function of venular microvessel endothelium. The results conformed to the hypothesis that epsilon-toxin interacts with vascular endothelial cells and increases the vessel wall permeability by direct damage of the endothelium. PMID:16041001

  9. 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

  10. Properties of single potassium channels modulated by glucose in rat pancreatic beta-cells.

    PubMed Central

    Ashcroft, F M; Ashcroft, S J; Harrison, D E

    1988-01-01

    1. The patch clamp method has been used to examine the effect of glucose on single K+ channel currents recorded from cell-attached patches on dissociated rat pancreatic beta-cells. Patch pipettes contained a 140 mM-K+ solution. 2. In glucose-free solution three types of K+ channels were observed. Two of these, having conductances of around 50 pS (G-channel) and 20 pS when the external K+ concentration, [K+]0, was 140 mM, were active at the resting potential of the cell. The G-channel was observed in more patches and showed higher activity; it therefore appears to contribute the major fraction of the resting K+ permeability of the beta-cell. At membrane potentials positive to about +20 mV a third type of K+ channel, having a mean conductance of 120 pS, was activated. The open probability of this channel was strongly voltage dependent and increased with depolarization. 3. The reversal potential of the G-channel current was shifted 59 mV by a 10-fold change in external K+ (Na+ substitution) indicating the channel is highly K+ selective. The single-channel conductance varied with [K+]o as predicted from the Goldman-Hodgkin-Katz equation; at physiological [K+]o (5 mM-K+) an inward conductance of around 10 pS is predicted. The amplitude of the single-channel current showed a tendency to saturate with increasing [K+]o. 4. Single G-channel currents show burst kinetics indicating at least two closed states. The open and closed (gap) times within the bursts were distributed exponentially with time constants of 2.5 ms (tau o) and 0.5 ms (tau c1) respectively at the resting potential of the cell. There was little change in tau c1 over the voltage range -40 to 60 mV (pipette potential) but tau o increased slightly with membrane depolarization. 5. The addition of glucose to the bath solution produced a reversible, dose-dependent decrease in G-channel activity. This decrease results principally from a reduction in the frequency and duration of the bursts of openings with

  11. Thyroid hormone effects on contractility and myosin composition of soleus muscle and single fibres from young and old rats.

    PubMed Central

    Li, X; Hughes, S M; Salviati, G; Teresi, A; Larsson, L

    1996-01-01

    1. Young (3-6 months) and old (20-24 months) male Wistar rat soleus muscles were examined for myosin isoform composition, fibre type, contractility and sarcoplasmic reticulum (SR) Ca2+ release properties either in control rats or in rats treated with thyroid hormone (3,5,3'-triiodothyronine, T3) for 4 weeks. 2. T3 treatment had a strong impact on myosin heavy chain (MyHC) and light chain (MyLC) isoform composition in both young and old rats. That is, all single fibres co-expressed type I and IIA (type I/IIA fibres) or type I, IIA and IIX MyHCs (type I/IIAX fibres) after treatment. Slow and fast MyLC isoforms, i.e. MyLC1s, MyLC1f, MyLC2s, MyLC2f and MyLC3, co-existed in each of the type I/IIA and I/IIAX fibres in variable proportions. 3. In old rats the maximum velocity of unloaded shortening (V0) was related to MyHC isoform composition: V0 for type I fibres was less than that for type I/IIA fibres which was less than that for type I/IIAX fibres. In young rats, on the other hand, V0 did not differ between pure type I fibres from controls and those co-expressing type I and type II MyHC isoforms from T3-treated rats. 4. Contraction and half-relaxation times of the isometric twitch were significantly longer in old than in young controls. This was paralleled by an age-related decrease in the caffeine threshold of the SR. Four weeks of T3 treatment eliminated the age-related differences in both speed of twitch contraction and caffeine thresholds. V0, on the other hand, was slower in old than in young animals, both control and T3-treated, when cells with a similar MyHC composition were compared. 5. In conclusion, thyroid hormone can substantially reverse at least some of the changes that occur in ageing muscle. Further, the age-related decline in V0 in soleus fibres from control and hyperthyroid rats suggests that: (1) the identification of beta/slow myosin isoforms is incomplete; or (2) the molecular characteristics of MyHC differ between young and old age; or (3) My

  12. Long-acting dihydropyridine calcium-channel blockers and sympathetic nervous system activity in hypertension: A literature review comparing amlodipine and nifedipine GITS

    PubMed Central

    Toal, Corey B.; Meredith, Peter A.; Elliott, Henry L.

    2012-01-01

    Calcium-channel blockers (CCBs) constitute a diverse group of compounds but are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized. Even within the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. Amlodipine and nifedipine in the gastrointestinal therapeutic system (GITS) formulation are the most studied of the once-daily CCBs. Amlodipine has an inherently long pharma-cokinetic half-life, whereas, in contrast, nifedipine has an inherently short half-life but in the GITS formulation the sophisticated delivery system allows for once-daily dosing. This article is derived from a systematic review of the published literature in hypertensive patients. The following search terms in three main databases (MEDLINE, Embase, Science Citation Index) from 1990 to 2011 were utilized: amlodipine, nifedipine, sympathetic nervous system, sympathetic response, sympathetic nerve activity, noradrenaline, norepinephrine and heart rate. More than 1500 articles were then screened to derive the relevant analysis. As markers of sympathetic nervous system activation, studies of plasma norepinephrine concentrations, power spectral analysis, muscle sympathetic nerve activity and norepinephrine spillover were reviewed. Overall, each drug lowered blood pressure in hypertensive patients in association with only small changes in heart rate (i.e. < 1 beat/min). Plasma norepinephrine concentrations, as the most widely reported marker of sympathetic nervous system activity, showed greater increases in patients treated with amlodipine than with nifedipine GITS. The evidence indicates that both these once-daily dihydropyridine CCBs lower blood pressure effectively with minimal effects on heart rate. There are small differences between the drugs in the extent to which each activates

  13. Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

    PubMed Central

    Nishi, K.; Sakanashi, M.; Takenaka, F.

    1974-01-01

    1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

  14. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    PubMed

    Du, Zhaojie; Wang, Lei; Zhao, Yinghua; Cao, Jian; Wang, Tao; Liu, Peng; Zhang, Yabo; Yang, Xinjie; Cheng, Xiaobing; Liu, Baolin; Lei, Delin

    2014-01-01

    The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE) in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3) in bone marrow mesenchymal stem cells (MSCs), and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1)-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2) and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3). Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor-2 (RUNX2), but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes. PMID:25144690

  15. Lamotrigine kidney distribution in male rats following a single intraperitoneal dose.

    PubMed

    Castel-Branco, M M; Falcão, A C; Figueiredo, I V; Macedo, T R A; Caramona, M M

    2004-02-01

    As it has been previously shown that lamotrigine (LTG) accumulates in the kidney of male rats, the purpose of the present investigation was to characterize the kidney profiles of LTG and its kidney distribution pattern in male rats, in order to confirm if a preferential distribution exists and to analyse if it does or does not affect the LTG systemic pharmacokinetics. Adult male Wistar rats were intraperitoneally injected with 5, 10 and 20 mg/kg of LTG. The concentration-time profiles of LTG in plasma and whole kidney were determined over 120 h postdose. The distribution of LTG in the rat kidney was investigated in another group of rats by measuring LTG levels in the renal cortex and medulla. The LTG plasma concentration-time profiles revealed a linear relationship with dose. However, a slight increase in the LTG elimination half-life with dose was observed. In contrast, a nonlinear relationship was established between LTG kidney levels and the dose administered. Consequently, nonparallel patterns were observed between LTG plasma and kidney profiles. The LTG kidney distribution pattern revealed an accumulation of LTG in the renal cortex. The present study demonstrated that LTG distributes preferentially to the kidneys of the male rat in a dose-dependent manner and suggests that such distribution may slightly affect the systemic kinetics of the drug. PMID:14748754

  16. Mitochondrial membrane potential in single living adult rat cardiac myocytes exposed to anoxia or metabolic inhibition.

    PubMed Central

    Di Lisa, F; Blank, P S; Colonna, R; Gambassi, G; Silverman, H S; Stern, M D; Hansford, R G

    1995-01-01

    1. The relation between mitochondrial membrane potential (delta psi m) and cell function was investigated in single adult rat cardiac myocytes during anoxia and reoxygenation. delta psi m was studied by loading myocytes with JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'- tetra-ethylbenzimidazolylcarbocyanine iodide), a fluorescent probe characterized by two emission peaks (539 and 597 nm with excitation at 490 nm) corresponding to monomer and aggregate forms of the dye. 2. De-energizing conditions applied to mitochondria, cell suspensions or single cells decreased the aggregate emission and increased the monomer emission. This latter result cannot be explained by changes of JC-1 concentration in the aqueous mitochondrial matrix phase indicating that hydrophobic interaction of the probe with membranes has to be taken into account to explain JC-1 fluorescence properties in isolated mitochondria or intact cells. 3. A different sensitivity of the two JC-1 forms to delta psi m changes was shown in isolated mitochondria by the effects of ADP and FCCP and the calibration with K+ diffusion potentials. The monomer emission was responsive to values of delta psi m below 140 mV, which hardly modified the aggregate emission. Thus JC-1 represents a unique double sensor which can provide semi-quantitative information in both low and high potential ranges. 4. At the onset of glucose-free anoxia the epifluorescence of individual myocytes studied in the single excitation (490 nm)-double emission (530 and 590 nm) mode showed a gradual decline of the aggregate emission, which reached a plateau while electrically stimulated (0.2 Hz) contraction was still retained. The subsequent failure of contraction was followed by the rise of the emission at 530 nm, corresponding to the monomer form of the dye, concomitantly with the development of rigor contracture. 5. The onset of the rigor was preceded by the increase in intracellular Mg2+ concentration ([Mg2+]i) monitored by mag-indo-1 epifluorescence

  17. Single voltage-dependent potassium channels in rat peripheral nerve membrane.

    PubMed Central

    Safronov, B V; Kampe, K; Vogel, W

    1993-01-01

    1. Voltage-dependent potassium channels were investigated in rat axonal membrane by means of the patch-clamp recording technique. Three different types of channels (F, I and S) have been characterized on the basis of their single-channel conductance, activation, deactivation and inactivation properties. 2. The fast (F) channels were activated smoothly at potentials (E) between -50 and 50 mV (E50 = 4.6 mV). They had a conductance of 55 pS for inward current and 30 pS for outward current in solutions containing 155 mM K+ (high K+) on both sides of the membrane at 21-23 degrees C. The F-channels demonstrated the fastest deactivation, within 1-2 ms, and inactivated in a few hundreds of milliseconds. The time constant of inactivation was 143 ms at E = +40 mV. 3. The intermediate (I) channels activated steeply between E = -70 and -50 mV (E50 = -64.2 mv) and had a single-channel conductance of 33 pS for inward and 18 ps for outward currents. The I-channels deactivated with intermediate kinetics with the time constants of 20.4 ms and 10.1 ms at E = -80 mV and E = -100 mV, respectively. Complete inactivation of the channels developed over tens of seconds. The time constant of inactivation was 7.4 s at E = +40 mV. 4. The slow (S) channels were active at potentials positive to -90 mV. Their conductance was 10 pS for inward currents. The time constant of activation of the S-channels was strongly potential dependent. At a holding potential of -100 mV the channels deactivated during a long time interval between 30 ms and 1 s, producing long-lasting tail currents. The mean time constant of deactivation for S-channels was 129 ms. 5. The conductances of F- and I-channels measured under normal physiological conditions (Ringer solution in bath) were 17 and 10 pS, respectively. 6. Tetraethylammonium (TEA), the classic blocker of potassium channels, suppressed F-, I- and S-channels. It gradually reduced the apparent amplitude of unitary currents in a dose-dependent manner with IC50

  18. In vivo assessment of diet-induced rat hepatic steatosis development by percutaneous single-fiber spectroscopy detects scattering spectral changes due to fatty infiltration

    NASA Astrophysics Data System (ADS)

    Piao, Daqing; Sultana, Nigar; Holyoak, G. Reed; Ritchey, Jerry W.; Wall, Corey R.; Murray, Jill K.; Bartels, Kenneth E.

    2015-11-01

    This study explores percutaneous single-fiber spectroscopy (SfS) of rat livers undergoing fatty infiltration. Eight test rats were fed a methionine-choline-deficient (MCD) diet, and four control rats were fed a normal diet. Two test rats and one control rat were euthanized on days 12, 28, 49, and 77 following initiation of the diet, after percutaneous SfS of the liver under transabdominal ultrasound guidance. Histology of each set of the two euthanized test rats showed mild and mild hepatic lipid accumulations on day 12, moderate and severe on day 28, severe and mild on day 49, and moderate and mild on day 77. Livers with moderate or higher lipid accumulation generally presented higher spectral reflectance intensity when compared to lean livers. Livers of the eight test rats on day 12, two of which had mild lipid accumulation, revealed an average scattering power of 0.37±0.14 in comparison to 0.07±0.14 for the four control rats (p<0.01). When livers of the test rats with various levels of fatty infiltration were combined, the average scattering power was 0.36±0.15 in comparison to 0.14±0.24 of the control rats (0.05

  19. Venous endothelin guides sympathetic innervation of the developing mouse heart

    PubMed Central

    Manousiouthakis, Eleana; Mendez, Monica; Garner, Madeline C.; Exertier, Prisca; Makita, Takako

    2014-01-01

    The mechanisms responsible for establishing correct target innervation during organ development are largely unknown. Sympathetic nerves traverse or follow blood vessels to reach their end-organs, suggesting the existence of vascular guidance cues that direct axonal extension. The sinoatrial node and the ventricle of the heart receive sympathetic innervation from the stellate ganglia (STG). Here we show that STG axons follow veins, specifically the superior vena cavae and sinus venosus, to reach these targets. We find that the election of these routes is determined by venous endothelium-derived endothelin-1, acting through its specific receptor Ednra expressed within a subpopulation of STG neurons. Furthermore, we demonstrate that Edn1-Ednra signaling is essential for functional regulation of the heart by sympathetic nerves. Our findings present venous Edn1 as a sympathetic guidance cue, and show how axon guidance mechanisms are coordinated with end-organ morphogenesis. PMID:24875861

  20. Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder

    PubMed Central

    2012-01-01

    Introduction Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS). The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter. Methods In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM). Levels of Cytochrome c (Cyt-C) was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM). The change of thiamine monophosphatase (TMP) levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM. Results Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS. Conclusions The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated with PTSD. PMID

  1. Schwanomma From Cervical Sympathetic Chain Ganglion - A Rare Presentation.

    PubMed

    Asma, A Affee; Kannah, E

    2015-10-01

    Schwanommas arising from cervical sympathetic chain are tumours that are rare in occurrence. These lesions are usually difficult to differentiate from a vagal schwanomma and a carotid body tumour during the initial workup. In this report, a rarely seen huge cervical sympathetic chain schwanomma case with partial Horner's syndrome is being presented in detail, which to our known knowledge, is one of the few cases reported in literature. PMID:26557566

  2. 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.

  3. Cytosolic calcium and myofilaments in single rat cardiac myocytes achieve a dynamic equilibrium during twitch relaxation.

    PubMed Central

    Spurgeon, H A; duBell, W H; Stern, M D; Sollott, S J; Ziman, B D; Silverman, H S; Capogrossi, M C; Talo, A; Lakatta, E G

    1992-01-01

    1. Single isolated rat cardiac myocytes were loaded with either the pentapotassium salt form or the acetoxymethyl ester (AM) form of the calcium-sensitive fluorescent probe, Indo-1. The relationship of the Indo-1 fluorescence transient, an index of the change in cytosolic calcium [Ca2+]i concentration, to the simultaneously measured cell length during the electrically stimulated twitch originating from slack length at 23 degrees C was evaluated. It was demonstrated that even if the Ca2+ dissociation rate from Indo-1 was assumed to be as slow as 10 s-1, the descending limb ('relaxation phase') of the Indo-1 fluorescence transient induced by excitation under these conditions is in equilibrium with the [Ca2+]i transient. Additionally, the extent of Indo-1 loading employed did not substantially alter the twitch characteristics. 2. A unique relationship between the fluorescence transient and cell length was observed during relaxation of contractions that varied in amplitude. This was manifest as a common trajectory in the cell length vs. [Ca2+]i phase-plane diagrams beginning at the time of cell relengthening. The common trajectory could also be demonstrated in Indo-1 AM-loaded cells. The Indo-1 fluorescence-length relation defined by this common trajectory is steeper than that described by the relation of peak contraction amplitude and peak fluorescence during the twitch contractions. 3. The trajectory of the [Ca2+]i-length relation elicited via an abrupt, rapid, brief (200 ms) pulse of caffeine directly onto the cell surface or by 'tetanization' of cells in the presence of ryanodine is identical to the common [Ca2+]i-length trajectory formed by electrically stimulated contractions of different magnitudes. As the [Ca2+]i and length transients induced by caffeine application or during tetanization in the presence of ryanodine develop with a much slower time course than those elicited by electrical stimulation, the common trajectory is not fortuitous, i.e. it cannot be

  4. Contribution of osmotic changes to disintegrative globulization of single cortical fibers isolated from rat lens.

    PubMed

    Wang, L F; Dhir, P; Bhatnagar, A; Srivastava, S K

    1997-08-01

    In this study the contribution of osmotic changes to disintegrative globulization of lens cortical fibers was examined. Single fiber cells were isolated by trypsinization of adult rat lens cortex, and morphological changes elicited by exposure to different external solutions were monitored optically. The survival of the fiber-shaped cells was analysed in accordance with the Weibull distribution. Changes in [Ca2+]i were measured using the fluorescent calcium-sensitive dye-Fluo-3. Exposure of isolated fiber cells to Ringer's solution (containing 2 mm Ca2+) led to an exponential increase in [Ca2+]i with a time constant of 10.2+/-0.8 min, and caused disintegrative globulization in 25+/-4 min (=Tg). The process of globulization as well as the rate of increase in [Ca2+]i was delayed by removing Cl- ions from the external media. Globulization was also delayed by adding 20% bovine serum albumin (Tg=107+/-3 min) or chloride channel inhibitors 5, nitro-2-(3-phenylpropylamino) benzoate (NPPB), dideoxyforskolin, niflumic acid, and tamoxifen. When the fiber cells were suspended in isotonic (280 mm sucrose) HEPES-sucrose (HS) or HEPES-EDTA-sucrose (HES) solution, no globulization was observed for an observation time of 120 min. However, exposure to hypotonic (180 mm) HES solution led to disintegration of fiber cells in 75+/-7 min. Disintegration of the fiber induced by hypotonic HES solution could be delayed by either 0. 05 mm leupeptin (Tg=97+/-6 min) or by pre-loading the fibers with BAPTA (Tg=100+/-4 min). Inhibition of membrane calcium transport by 0.5 mm La3+ had no effect on Tg in hypotonic HES. Addition of 2 mm Ca2+ to HES solution accelerated globulization, and Tg was 57+/-4, 69+/-5 and 102+/-6 min for hypo-, iso- and hyper- tonic solutions, respectively. Transient exposure to calcium also accelerated disintegrative globulization of fiber cells exposed subsequently to HES solution. These results suggest that in ionic media, part of the calcium influx in isolated fiber

  5. Vibrational Spectroscopy of Sympathetically Cooled CaH^+ Molecular Ions

    NASA Astrophysics Data System (ADS)

    Khanyile, Ncamiso B.; Goeders, James E.; Brown, Kenneth R.

    2013-06-01

    The search for time variation in the fundamental constants of nature such as the fine structure constant(α) and the proton/electron mass ratio(μ), is an area of active research. Comparing the vibrational overtones of CaH^+ with electronic transitions in atoms has been proposed as a means to detect possible time variation of μ Before these precision measurements can be realized, the survey spectroscopy needs to be performed. We describe our experiments using a Coulomb crystal of sympathetically cooled CaH^+ and laser-cooled Ca^+ ions to measure the vibrational overtones by resonance-enhanced multiphoton photo-dissociation (REMPD) in a linear Paul trap. The dissociation of CaH^+ is detected by observing the change in the crystal composition by monitoring the Ca^+ fluorescence. Future single ion experiments for the precision measurement are also discussed. J. Uzan, Rev. Mod. Phys. 75, 403 (2003). M. Kajita and Y. Moriwaki, J. Phys. B: At. Mol. Opt. Phys. 42, 154022(2009).

  6. 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. PMID:25767284

  7. Cardiovascular sympathetic arousal in response to different mental stressors.

    PubMed

    Mestanik, M; Mestanikova, A; Visnovcova, Z; Calkovska, A; Tonhajzerova, I

    2016-01-01

    The altered regulation of autonomic response to mental stress can result in increased cardiovascular risk. The laboratory tests used to simulate the autonomic responses to real-life stressors do not necessarily induce generalized sympathetic activation; therefore, the assessment of regulatory outputs to different effector organs could be important. We aimed to study the cardiovascular sympathetic arousal in response to different mental stressors (Stroop test, mental arithmetic test) in 20 healthy students. The conceivable sympathetic vascular index - spectral power of low frequency band of systolic arterial pressure variability (LF-SAP) and novel potential cardio-sympathetic index - symbolic dynamics heart rate variability index 0V% were evaluated. The heart and vessels responded differently to mental stress - while Stroop test induced increase of both 0V% and LF-SAP indices suggesting complex sympathetic arousal, mental arithmetic test evoked only 0V% increase compared to baseline (p<0.01, p<0.001, p<0.01, respectively). Significantly greater reactivity of LF-SAP, 0V%, heart rate (HR) and mean arterial pressure (MAP) were found in response to Stroop test compared to mental arithmetic test potentially indicating the effect of different central processing (0V%, LF-SAP: p<0.001; HR, MAP: p<0.01). The different effectors' sympathetic responses to cognitive stressors could provide novel important information regarding potential pathomechanisms of stress-related diseases. PMID:26674281

  8. Influence of gravitational sympathetic stimulation on the Surgical Plethysmographic Index.

    PubMed

    Colombo, R; Marchi, A; Borghi, B; Fossali, T; Tobaldini, E; Guzzetti, S; Raimondi, F

    2015-01-01

    Surgical Plethysmographic Index (SPI), calculated from pulse photo-plethysmographic amplitude oscillations, has been proposed as a tool to measure nociception anti-nociception balance during general anesthesia, but it is affected by several confounding factor that alter the autonomic nervous system (ANS) modulation. We hypothesized that SPI may be mainly affected by sympathetic stimulation independently from nociception. We studied the effects of two sympathetic stimuli on SPI, delivered through passive head-up tilt at 45 and 90 degrees angles, in nine awake healthy adults. The sympathetic modulation was assessed by means of heart rate variability (HRV) analysis. Mean (SD) SPI significantly increased from baseline to 45 degrees [from 38.6 (13.7) to 60.8 (7.6), p<0.001)] and to 90 degrees angle tilt [82.3 (5.4), p<0.001]. The electrocardiographic mean R-to-R interval significantly shortened during both passive tilts, whereas systolic arterial pressure did not change during the study protocol. HRV changed significantly during the study protocol towards a predominance of sympathetic modulation during passive tilt. Gravitational sympathetic stimulation at two increasing angles, in absence of any painful stimuli, affects SPI in awake healthy volunteers. SPI seems to reflect the sympathetic outflow directed to peripheral vessels. PMID:25317683

  9. 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

  10. 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.

  11. Excretion of Morroniside in Rat Urine After Single Oral and Intravenous Administration.

    PubMed

    Xiong, Shan; Li, Jinglai; Zhang, Zhenqing

    2016-07-01

    This study was designed to develop a sensitive, simple and rapid method for the quantitation of morroniside in rat urine using high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) and to investigate the excretion of morroniside in rat urine. The mobile phase consisted of water-acetonitrile (gradient elution) at a flow rate of 0.4 mL/min. Detection was performed using positive-ion electrospray ionization in multiple reaction monitoring (MRM) modes. And the detection of morroniside in rat urine by the LC-MS-MS was accurate and precise from 1.0 to 2,500 ng/mL (a correlation coefficient of 0.9953). The recoveries and matrix effects were all in line with the biological sample measurement requirements. The intraday accuracy was 88.68-105.78% with precision of 6.50-11.19% and the interday accuracy was 95.77-102.43% with precision of 7.08-10.40%. Excretion data of morroniside in rat urine indicated that 21.43‰ (i.g.) and 100.35% (i.v.) of the dose administered was excreted as unconverted form, respectively. And the maximal excretion rate was 27.57 and 482.42 μg/h after oral and intravenous administration, respectively. These results indicated that the developed method has satisfactory sensitivity, accuracy and precision for the quantification of morroniside in rat urine. PMID:26896349

  12. Pulmonary chemoreflex and phrenic sympathetic efferents.

    PubMed

    Bałkowiec, A; Szulczyk, P

    1993-11-01

    The pulmonary chemoreflex components such as reactions of phrenic sympathetic neuron (PhSN) activity, phrenic nerve activity, heart rate and blood pressure were tested in chloralose-anesthetized, paralyzed cats. 10 micrograms to 160 micrograms phenylbiguanide (PBG) in 0.9% NaCl was injected into the pulmonary circulation. PBG injected into the right atrium (in 11 of 19 experiments) and into the pulmonary artery (in 5 of 8 experiments), evoked short-latency (1-1.4 sec) dose-dependent increase in PhSN activity accompanied by increase in blood pressure, and followed by decrease in these two variables. In all experiments, activity of the phrenic nerve was depressed, and bradycardia occurred after PBG injection. All responses to PBG injections into the pulmonary artery were abolished following bilateral vagotomy. In the same procedure related to the right atrium after vagotomy, the increases in PhSN activity and blood pressure were also abolished, although a decrease in heart rate, PhSN activity and in the amplitude of phrenic nerve discharges together with an increase in their frequency persisted. Our results suggest that short-latency increase in PhSN activity is a component of pulmonary chemoreflex. PMID:8272587

  13. Comparisons of the clinical outcomes of thoracoscopic sympathetic surgery for palmar hyperhidrosis: R4 sympathicotomy versus R4 sympathetic clipping versus R3 sympathetic clipping

    PubMed Central

    Joo, Seok; Haam, Seokjin; Lee, Sungsoo

    2016-01-01

    Background Thoracoscopic sympathetic surgery is regarded as a definitive treatment for palmar hyperhidrosis. However, the optimal surgical strategy remains unclear. The aim of this study was to compare outcomes based on the level and type of sympathetic disconnection in patients with palmar hyperhidrosis. Methods From January 2009 to December 2014, 101 patients with palmar hyperhidrosis underwent thoracoscopic sympathetic surgery at Gangnam Severance Hospital. Complete follow-up information was obtained from 59 patients. We retrospectively analyzed the results of operation, degree of palmar sweating (%), grade of compensatory sweating (none, mild, moderate, severe, very severe), grade of satisfaction (very satisfied, satisfied, moderate, dissatisfied, very dissatisfied), and recurrence/failure. Results R4 sympathicotomy, R4 sympathetic clipping, and R3 sympathetic clipping were performed in 16, 20, and 23 patients, respectively. The mean degree of palmar sweating after sympathetic surgery was not significantly different between these three groups (17.50% vs. 27.00% vs. 29.78%; P=0.38). The rate of life-bothering compensatory sweating was lower in the R4 sympathicotomy group compared with those of other two groups (0% vs. 25%, 47.8%; P=0.09). The rate of very satisfied to moderate grades of satisfaction were lower in the R3 sympathetic clipping group compared with those of other two groups (93.8%, 100% vs. 73.9%; P=0.07). The rate of recurrence/failure rates were lower in the R4 sympathicotomy group compared with those of other two groups (12.50% vs. 35.00%, 34.8%; P=0.25). Sympathetic surgery at the R3 level was the only significant risk factor for patient dissatisfaction (odd ratio =12.353, 95% confidence interval =1.376–110.914; P=0.025). Conclusions Our data support that R4 sympathicotomy had lower grades of compensatory sweating, higher grades of satisfaction, and lower rates of recurrence/failure. We therefore consider R4 sympathicotomy as an optimal

  14. EFFECT OF SINGLE VERSUS SPLIT DOSES OF DIETHYINITROSAMINE ON THE INDUCTION OF GAMMA-GLUTAMYLTRANSPEPTIDASE-FOCI IN THE LIVERS OF ADULT AND JUVENILE RATS

    EPA Science Inventory

    The induction of gamma-glutamyltranspeptidase (GGT)-foci by single and by split doses of diethylnitrosamine (DENA) was evaluated in the livers of juvenile and young adult male, Sprague-Dawley rats. A single dose of DENA was administered at either 32, 41 or 52 days of age and foll...

  15. The effects on the rat testis of single inhalation exposures to ethylene glycol monoalkyl ethers, in particular ethylene glycol monomethyl ether.

    PubMed

    Samuels, D M; Doe, J E; Tinston, D J

    1984-01-01

    The effects of a single inhalation exposure to the rat of the saturated vapours derived from four ethylene glycol monoalkyl ethers have been investigated. No effects on the testis were observed following exposure to ethylene glycol isopropyl ether (EG ISOPE) and ethylene glycol butyl ether (EGBE), but there were marked reductions in testicular weight 14 days after exposure to ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE). Further studies were designed to establish the effect of a single exposure to EGME. Mature male albino rats were exposed to various levels of EGME vapour for a single 4-h period and killed 14 days later. Following this single exposure a dose-related decrease in testis weight was observed in rats exposed to 5,000, 2,500 or 1,250 ppm EGME. Histopathological examination revealed disordered spermatogenesis and tubular atrophy in these animals. Minimal degenerative changes were seen in the testis of rats exposed to 625 ppm EGME. When rats were examined at various time intervals after exposure to EGME vapour for 4 h, testis weight was reduced in rats examined 2 days after exposure to 2,500 and 1,000 ppm EGME and remained depressed when compared with control values for up to 19 days following exposure. Histopathological examination of the testis revealed disordered spermatogenesis in exposed animals evident at 1 day following exposure to either 2,500 or 1,00 ppm EGME. PMID:6595980

  16. Cellular Inflammatory Infiltrate in Pneumonitis Induced by a Single Moderate Dose of Thoracic X Radiation in Rats

    PubMed Central

    Szabo, Sara; Ghosh, Swarajit N.; Fish, Brian L.; Bodiga, Sreedhar; Tomic, Rade; Kumar, Gagan; Morrow, Natalya V.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2010-01-01

    The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10- or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis. PMID:20334527

  17. Coping with dehydration: sympathetic activation and regulation of glutamatergic transmission in the hypothalamic PVN.

    PubMed

    Bardgett, Megan E; Chen, Qing-Hui; Guo, Qing; Calderon, Alfredo S; Andrade, Mary Ann; Toney, Glenn M

    2014-06-01

    Autonomic and endocrine profiles of chronic hypertension and heart failure resemble those of acute dehydration. Importantly, all of these conditions are associated with exaggerated sympathetic nerve activity (SNA) driven by glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here, studies sought to gain insight into mechanisms of disease by determining the role of PVN ionotropic glutamate receptors in supporting SNA and mean arterial pressure (MAP) during dehydration and by elucidating mechanisms regulating receptor activity. Blockade of PVN N-methyl-D-aspartate (NMDA) receptors reduced (P < 0.01) renal SNA and MAP in urethane-chloralose-anesthetized dehydrated (DH) (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls. Blockade of PVN α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors had no effect in either group. NMDA in PVN caused dose-dependent increases of renal SNA and MAP in both groups, but the maximum agonist evoked response (Emax) of the renal SNA response was greater (P < 0.05) in DH rats. The latter was not explained by increased PVN expression of NMDA receptor NR1 subunit protein, increased PVN neuronal excitability, or decreased brain water content. Interestingly, PVN injection of the pan-specific excitatory amino acid transporter (EAAT) inhibitor DL-threo-β-benzyloxyaspartic acid produced smaller sympathoexcitatory and pressor responses in DH rats, which was associated with reduced glial expression of EAAT2 in PVN. Like chronic hypertension and heart failure, dehydration increases excitatory NMDA receptor tone in PVN. Reduced glial-mediated glutamate uptake was identified as a key contributing factor. Defective glutamate uptake in PVN could therefore be an important, but as yet unexplored, mechanism driving sympathetic hyperactivity in chronic cardiovascular diseases. PMID:24671240

  18. Comparative metabolism studies of hexabromocyclododecane (HBCD) diastereomers in male rats following a single oral dose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively 42% of dose for alpha-HBCD,...

  19. Muscle glucose uptake in the rat after suspension with single hindlimb weight bearing

    NASA Technical Reports Server (NTRS)

    Stump, Craig S.; Woodman, Christopher R.; Fregosi, Ralph F.; Tipton, Charles M.

    1993-01-01

    An examination is conducted of the effect of nonweight-bearing conditions, and the systemic influences of simulated microgravity on rat hindlimb muscles. The results obtained suggest that the increases in hindlimb muscle glucose uptake and extracellular space associated with simulated microgravity persist with hindlimb weightbearing, despite the prevention of muscle atrophy. The mechanism (or mechanisms) responsible for these effects are currently unknown.

  20. Potential role of TCF7L2 gene variants on cardiac sympathetic/parasympathetic activity

    PubMed Central

    Boccardi, Virginia; Ambrosino, Immacolata; Papa, Michela; Fiore, Daniela; Rizzo, Maria Rosaria; Paolisso, Giuseppe; Barbieri, Michelangela

    2010-01-01

    Variants in transcription factor 7-like 2 (266096218TCF7L2266096218USuser266096218Gene names have been italicized per house style. Please check and confirm whether there are other instances that need to be italicized or instances where italics have been inappropriately applied.) gene have been found strongly associated with an increased risk of type 2 diabetes, as well as with an impairment of glucagon-like peptide-1 (GLP-1) signalling chain. In rats, stimulation of central GLP-1 receptors increases heart rate and activates autonomic regulatory neurons. We aimed to evaluate the potential role of TCF7L2 gene polymorphisms on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration after glucose ingestion. Genotyping was performed for rs12255372 and rs7903146 TCF7L2 gene variants in 250 non-related healthy volunteers (mean age 27±3 years). Consistent with previous reports, both single-nucleotide polymorphisms were in strong linkage disequilibrium (D′=0.87, r2=0.76). A subset of 167 patients underwent an oral glucose tolerance test while a continuous recording of heart rate variability was performed. At baseline, no differences in fasting plasma insulin, in GLP-1 levels and in LF/HF (low frequency/high frequency) ratio between the three genotypes were found. Along with glucose ingestion TT subjects had lower INSAUC (insulin area under curve), as well as higher LF/HFAUC (LF/HF area under curve) values. No difference in GLP-1AUC (GLP-1 area under curve) between TCF7L2 gene variants was found. A multivariate analysis including multiple covariates showed that only INSAUC, GLP-1AUC and TCF7L2 gene variants were independently associated with LF/HFAUC. In conclusion, TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity. Moreover, such effect is independent of GLP-1 and insulin plasma concentrations suggesting a potential role of such gene variants in

  1. [Diagnostic and treatment measures in patients with sympathetically maintained pain].

    PubMed

    Maier, C; Gleim, M

    1998-08-27

    The term "sympathetically maintained pain" (SMP) describes a symptom that might accompany a variety of diseases (CRPS, (post-) herpetic and post-injury neuralgia), which might transform into sympathetically independent pain (SIP) after some time. Patients with SMP present a bunch of disorders of the autonomic and sensory system, but the only reliable way to diagnose a pain as SMP is a positive response to an intervention at the sympathetic nervous system. Three ways of influencing the sympathetic system are commonly used: (a) local anesthetic sympathetic blockade (SB), (b) intravenous regional sympathectomy (IVRS) and (c) ganglionic local opioid application (GLOA). A review of current literature shows that SB has certain advantages in diagnostic sensitivity, whereas GLOA might be slightly superior in therapy of some diseases with longstanding pain history. Obviously, the therapeutic benefit of all interventions is complete independent of the accompanying autonomic disorder and of a blockade of efferent fibers. A new heuristic model of the SMP mechanism is presented, including both experimental and clinical data. For reducing the risks of false positive or negative diagnosis of SMP and SIP, a diagnostic algorithm is proposed. This includes optimizing the technique, changes of interventional measures, and adequate monitoring both of analgesia and as well of the extend of efferent sympathetic blockade (e.g. measurement of sympathetic reflexes). The treatment recommendations in patients with SMP vary in dependence of the kind of disease. In SMP, invasive measures play an important, but only limited role within the comprehensive treatment concept. As an example a three-stage, symptom-adapted treatment algorithm is demonstrated for CRPS, including also drug therapy, psychologic and physiotherapeutic approaches. PMID:12799969

  2. Study of Intravenous Single-Dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Kwon, Ki-Rok; Yu, Jun-Sang; Sun, Seung-Ho; Lee, Kwang-Ho

    2016-01-01

    Objectives: Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single- dose test with sprague-dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/ animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. Results: No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. Conclusion: The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal. PMID:27386149

  3. Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

    PubMed Central

    Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

  4. Surface area as a dose metric for carbon black nanoparticles: A study of oxidative stress, DNA single-strand breakage and inflammation in rats

    NASA Astrophysics Data System (ADS)

    Chuang, Hsiao-Chi; Chen, Li-Chen; Lei, Yu-Chen; Wu, Kuen-Yuh; Feng, Po-Hao; Cheng, Tsun-Jen

    2015-04-01

    Combustion-derived nanoparticles are characterised by a high surface area (SA) per mass. SA is proposed to regulate the bioreactivity of nanoparticles; however, the dose metric for carbon black remains controversial. To determine the relationships between bioreactivity and SA, male spontaneously hypertensive rats were exposed to carbon black (CB) nanoparticles (15, 51 and 95 nm) via intratracheal instillation for 24 h. Pulmonary exposure to CB resulted in a significant increase in systemic 8-hydroxy-2‧-deoxyguanosine (8-OHdG), DNA single-strand breakages in peripheral blood cells and pulmonary cell infiltration in rats. The oxidative potential and particularly the corresponding SA of CB were correlated with the level of 8-OHdG, DNA single-strand breakages and pulmonary cell infiltration in rats. We conclude that SA is an important dose metric for CB that can regulate oxidative stress and DNA damage in rats. Furthermore, this observation was more significant for smaller sized CB.

  5. Neutral gas sympathetic cooling of an ion in a Paul trap.

    PubMed

    Chen, Kuang; Sullivan, Scott T; Hudson, Eric R

    2014-04-11

    A single ion immersed in a neutral buffer gas is studied. An analytical model is developed that gives a complete description of the dynamics and steady-state properties of the ions. An extension of this model, using techniques employed in the mathematics of economics and finance, is used to explain the recent observation of non-Maxwellian statistics for these systems. Taken together, these results offer an explanation of the long-standing issues associated with sympathetic cooling of an ion by a neutral buffer gas. PMID:24765957

  6. Neutral Gas Sympathetic Cooling of an Ion in a Paul Trap

    NASA Astrophysics Data System (ADS)

    Chen, Kuang; Sullivan, Scott T.; Hudson, Eric R.

    2014-04-01

    A single ion immersed in a neutral buffer gas is studied. An analytical model is developed that gives a complete description of the dynamics and steady-state properties of the ions. An extension of this model, using techniques employed in the mathematics of economics and finance, is used to explain the recent observation of non-Maxwellian statistics for these systems. Taken together, these results offer an explanation of the long-standing issues associated with sympathetic cooling of an ion by a neutral buffer gas.

  7. Baroreflex Function in Rats after Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Hasser, Eileen M.

    1997-01-01

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

  8. Fiber type effects on contraction-stimulated glucose uptake and GLUT4 abundance in single fibers from rat skeletal muscle

    PubMed Central

    Castorena, Carlos M.; Arias, Edward B.; Sharma, Naveen; Bogan, Jonathan S.

    2014-01-01

    To fully understand skeletal muscle at the cellular level, it is essential to evaluate single muscle fibers. Accordingly, the major goals of this study were to determine if there are fiber type-related differences in single fibers from rat skeletal muscle for: 1) contraction-stimulated glucose uptake and/or 2) the abundance of GLUT4 and other metabolically relevant proteins. Paired epitrochlearis muscles isolated from Wistar rats were either electrically stimulated to contract (E-Stim) or remained resting (No E-Stim). Single fibers isolated from muscles incubated with 2-deoxy-d-[3H]glucose (2-DG) were used to determine fiber type [myosin heavy chain (MHC) isoform protein expression], 2-DG uptake, and abundance of metabolically relevant proteins, including the GLUT4 glucose transporter. E-Stim, relative to No E-Stim, fibers had greater (P < 0.05) 2-DG uptake for each of the isolated fiber types (MHC-IIa, MHC-IIax, MHC-IIx, MHC-IIxb, and MHC-IIb). However, 2-DG uptake for E-Stim fibers was not significantly different among these five fiber types. GLUT4, tethering protein containing a UBX domain for GLUT4 (TUG), cytochrome c oxidase IV (COX IV), and filamin C protein levels were significantly greater (P < 0.05) in MHC-IIa vs. MHC-IIx, MHC-IIxb, or MHC-IIb fibers. TUG and COX IV in either MHC-IIax or MHC-IIx fibers exceeded values for MHC-IIxb or MHC-IIb fibers. GLUT4 levels for MHC-IIax fibers exceeded MHC-IIxb fibers. GLUT4, COX IV, filamin C, and TUG abundance in single fibers was significantly (P < 0.05) correlated with each other. Differences in GLUT4 abundance among the fiber types were not accompanied by significant differences in contraction-stimulated glucose uptake. PMID:25491725

  9. The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation.

    PubMed

    Pritchard, J N; Holmes, A; Evans, J C; Evans, N; Evans, R J; Morgan, A

    1985-04-01

    A comparison was made of the distribution of dust in the rat lung following its administration by inhalation and by a single intratracheal instillation. Due to the wide variety of instillation techniques, an "average" method was adopted based on the results from a survey of 15 laboratories in Europe and the USA. Novel techniques were developed to quantify the distribution of dust within the lung both microscopically and macroscopically. The distribution of dust obtained by instillation was shown to be much less homogeneous that that obtained by inhalation and penetration to the periphery was minimal. The effects of (a) changing the volume of suspension, (b) changing the concentration of the suspension, and (c) introducing air into the syringe were investigated. Although the use of air in the syringe was beneficial, none of the other modifications effected any improvement in the distribution. The difference in distribution following inhalation and instillation leads to the conclusion that the latter may be of use in establishing the nature and comparative response of the lung to different dusts, but not for establishing an absolute dose-response relationship. It is recommended that no more than 1 mg of fibrous or 5 mg of nonfibrous dust be given in a single instillation to adult rats. PMID:3979359

  10. Sudomotor function in sympathetic reflex dystrophy.

    PubMed

    Birklein, F; Sittl, R; Spitzer, A; Claus, D; Neundörfer, B; Handwerker, H O

    1997-01-01

    Sudomotor functions were studied in 27 patients suffering from reflex sympathetic dystrophy (RSD) according to the criteria established by Bonica (18 women, 9 men; mean age 50 +/- 12.3 years; median duration of disease 8 weeks, range 2-468 weeks). To measure local sweating rates, two small chambers (5 cm2) were affixed to corresponding areas of hairy skin on the affected and unaffected limbs. Dry nitrogen gas was passed through the chambers (270 ml/min) and evaporation was recorded at both devices with hygrometers. Thermoregulatory sweating (TST) was induced by raising body temperature (intake of 0.5 1 hot tea and infra-red irradiation). Local sweating was also induced through an axon reflex (QSART) by transcutaneous iontophoretic application of carbachol (5 min, 1 mA). In addition, skin temperature was measured on the affected and unaffected side by infra-red thermography. Mean skin temperature was significantly higher on the affected side (P < 0.003). In spite of the temperature differences, there was no difference in basal sweating on the affected and unaffected side. However, both methods of sudomotor stimulation lead to significantly greater sweating responses on the affected compared to the unaffected side (TST: P < 0.05, QSART: P < 0.004). Latency to onset of sweating was significantly shorter on the affected side under both test conditions (P < 0.04 and P < 0.003, respectively). Sweat responses were not correlated to absolute skin temperature but were probably related to the increased blood flow on the affected side. Our findings imply a differential disturbance of vasomotor and sudomotor mechanisms in affected skin. Whereas vasoconstrictor activity is apparently lowered, sudomotor output is either unaltered or may even be enhanced. PMID:9060012

  11. Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

    PubMed Central

    Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

    2015-01-01

    Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

  12. Segregation of Acetylcholine and GABA in the Rat Superior Cervical Ganglia: Functional Correlation.

    PubMed

    Elinos, Diana; Rodríguez, Raúl; Martínez, Luis Andres; Zetina, María Elena; Cifuentes, Fredy; Morales, Miguel Angel

    2016-01-01

    Sympathetic neurons have the capability to segregate their neurotransmitters (NTs) and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh) and other classical NTs such as gamma aminobutyric acid (GABA). Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX). We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level of segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region showed larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons. PMID:27092054

  13. Segregation of Acetylcholine and GABA in the Rat Superior Cervical Ganglia: Functional Correlation

    PubMed Central

    Elinos, Diana; Rodríguez, Raúl; Martínez, Luis Andres; Zetina, María Elena; Cifuentes, Fredy; Morales, Miguel Angel

    2016-01-01

    Sympathetic neurons have the capability to segregate their neurotransmitters (NTs) and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh) and other classical NTs such as gamma aminobutyric acid (GABA). Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX). We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level of segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region showed larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons. PMID:27092054

  14. TrkB/BDNF signalling patterns the sympathetic nervous system

    PubMed Central

    Kasemeier-Kulesa, Jennifer C.; Morrison, Jason A.; Lefcort, Frances; Kulesa, Paul M.

    2015-01-01

    The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of ‘primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system. PMID:26404565

  15. Reflex carotid body chemoreceptor control of phrenic sympathetic neurons.

    PubMed

    Bałkowiec, A; Revenko, S; Szulczyk, P

    1993-04-01

    The reflex reaction of phrenic sympathetic neurons to stimulation of carotid body chemoreceptors was tested in chloralose-anesthetized and paralyzed cats with both vago-aortic nerves cut. During systemic hypoxia (animals ventilated with 10% O2 in N2) the sympathetic phrenic nerve activity increased from 100% in the control to 269%. This increase was markedly attenuated after cutting both sinus nerves. Reflex excitatory response in phrenic sympathetic neurons with the latency of 150 msec was evoked by electrical stimulation of the right carotid sinus nerve (3 pulses of 0.2 msec, 333 Hz). The central transmission time of the reflex was about 90 msec. Injecting 0.1 ml of 1 M NaHCO3 saturated with CO2 (in order to activate carotid body chemoreceptors) into the right or left carotid sinus, evoked excitatory responses in sympathetic neurons regardless of the side. The stimulation of carotid body chemoreceptors also increased somatic phrenic nerve activity. The three methods applied to the stimulation of carotid body chemoreceptors produced increase of phrenic nerve sympathetic activity. PMID:8390088

  16. Sympathetic control of bone mass regulated by osteopontin

    PubMed Central

    Nagao, Masashi; Feinstein, Timothy N.; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Saita, Yoshitomo; Hanyu, Ryo; Hemmi, Hiroaki; Izu, Yayoi; Takeda, Shu; Wang, Kathryn; Rittling, Susan; Nakamoto, Tetsuya; Kaneko, Kazuo; Kurosawa, Hisashi; Karsenty, Gerard; Denhardt, David T.; Vilardaga, Jean-Pierre; Noda, Masaki

    2011-01-01

    The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the β2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the β2-adrenergic receptor/cAMP signaling system. PMID:21990347

  17. 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

  18. Effect of the culture extract of Lentinus edodes mycelia on splenic sympathetic activity and cancer cell proliferation.

    PubMed

    Shen, Jiao; Tanida, Mamoru; Fujisaki, Yoshiyuki; Horii, Yuko; Hashimoto, Kazuko; Nagai, Katsuya

    2009-01-28

    The spleen is an important organ for tumor immunity, and the splenic sympathetic nerve has a suppressive effect on splenic natural killer (NK) cytotoxicity. On the basis of this and reports that Lentinus edodes (Shiitake mushroom) has tumor-inhibitory effects, the authors hypothesized that an extract of a mycelial culture of L. edodes grown in a solid medium of sugar-cane bagasse and defatted rice bran-L.E.M-might affect the sympathetic splenic sympathetic nerve activity (Splenic-SNA) and thus inhibit tumor proliferation. Thus, the effect of L.E.M on Splenic-SNA and human cancer cell proliferation was examined. Splenic-SNA was found to be suppressed by an intraduodenal L.E.M injection in urethane-anesthetized rats, which significantly inhibited increases in the tumor volume of human colon and breast cancer cells implanted in athymic nude mice. These findings suggest that L.E.M has an inhibitory effect on tumor proliferation possibly via a reduction in NK cytotoxicity through the suppression of Splenic-SNA. PMID:19059811

  19. Comparative long-term toxicity of Libby amphibole and amosite asbestos in rats after single or multiple intratracheal exposures.

    PubMed

    Cyphert, Jaime M; Carlin, Danielle J; Nyska, Abraham; Schladweiler, Mette C; Ledbetter, Allen D; Shannahan, Jonathan H; Kodavanti, Urmila P; Gavett, Stephen H

    2015-01-01

    In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures. PMID:25506632

  20. Single-Dose Local Simvastatin Injection Improves Implant Fixation via Increased Angiogenesis and Bone Formation in an Ovariectomized Rat Model

    PubMed Central

    Tan, Jie; Yang, Ning; Fu, Xin; Cui, Yueyi; Guo, Qi; Ma, Teng; Yin, Xiaoxue; Leng, Huijie; Song, Chunli

    2015-01-01

    Background Statins have been reported to promote bone formation. However, taken orally, their bioavailability is low to the bones. Implant therapies require a local repair response, topical application of osteoinductive agents, or biomaterials that promote implant fixation. Material/Methods The present study evaluated the effect of a single local injection of simvastatin on screw fixation in an ovariectomized rat model of osteoporosis. Results Dual-energy X-ray absorptiometry, micro-computed tomography, histology, and biomechanical tests revealed that 5 and 10 mg simvastatin significantly improved bone mineral density by 18.2% and 22.4%, respectively (P<0.05); increased bone volume fraction by 51.0% and 57.9%, trabecular thickness by 16.4% and 18.9%, trabeculae number by 112.0% and 107.1%, and percentage of osseointegration by 115.7% and 126.3%; and decreased trabeculae separation by 34.1% and 36.6%, respectively (all P<0.01). Bone mineral apposition rate was significantly increased (P<0.01). Furthermore, implant fixation was significantly increased (P<0.05), and bone morphogenetic protein 2 (BMP2) expression was markedly increased. Local injection of a single dose of simvastatin also promoted angiogenesis. Vessel number, volume, thickness, surface area, and vascular volume per tissue volume were significantly increased (all P<0.01). Vascular endothelial growth factor (VEGF), VEGF receptor-2, von Willebrand factor, and platelet endothelial cell adhesion molecule-1 expression were enhanced. Conclusions A single local injection of simvastatin significantly increased bone formation, promoted osseointegration, and enhanced implant fixation in ovariectomized rats. The underlying mechanism appears to involve enhanced BMP2 expression and angiogenesis in the target bone. PMID:25982481

  1. Renal sympathetic denervation for the treatment of refractory hypertension.

    PubMed

    Leong, Kui Toh Gerard; Walton, Antony; Krum, Henry

    2014-01-01

    Resistant hypertension poses significant health concerns. There are strong demands for new and safe therapies to control resistant hypertension while addressing its common causes, specifically poor compliance to lifelong polypharmacy, lifestyle modifications, and physician inertia. The sympathetic nervous system plays a significant pathophysiological role in hypertension. Surgical sympathectomy for blood pressure reduction is an old but extremely efficacious therapeutic concept, now abandoned with the dawn of a safer contemporary pharmacology era. Recently, clinical studies have revealed promising results for safe and sustained blood pressure reduction with percutaneous renal sympathetic denervation. This is a novel, minimally invasive, device-based therapy, specifically targeting and ablating the renal artery nerves with radiofrequency waves without permanent implantation. There are also reported additional benefits in related comorbidities, such as impaired glucose metabolism, renal impairment, left ventricular hypertrophy, heart failure, and others. This review focuses on how selective renal sympathetic denervation works, its present and potential therapeutic indications, and its future directions. PMID:24422574

  2. Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons.

    PubMed

    Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne

    2015-06-23

    The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation. PMID:26074079

  3. Blood pressure is maintained during dehydration by hypothalamic paraventricular nucleus-driven tonic sympathetic nerve activity

    PubMed Central

    Holbein, Walter W; Bardgett, Megan E; Toney, Glenn M

    2014-01-01

    Resting sympathetic nerve activity (SNA) consists primarily of respiratory and cardiac rhythmic bursts of action potentials. During homeostatic challenges such as dehydration, the hypothalamic paraventricular nucleus (PVN) is activated and drives SNA in support of arterial pressure (AP). Given that PVN neurones project to brainstem cardio-respiratory regions that generate bursting patterns of SNA, we sought to determine the contribution of PVN to support of rhythmic bursting of SNA during dehydration and to elucidate which bursts dominantly contribute to maintenance of AP. Euhydrated (EH) and dehydrated (DH) (48 h water deprived) rats were anaesthetized, bilaterally vagotomized and underwent acute PVN inhibition by bilateral injection of the GABA-A receptor agonist muscimol (0.1 nmol in 50 nl). Consistent with previous studies, muscimol had no effect in EH rats (n = 6), but reduced mean AP (MAP; P < 0.001) and integrated splanchnic SNA (sSNA; P < 0.001) in DH rats (n = 6). Arterial pulse pressure was unaffected in both groups. Muscimol reduced burst frequency of phrenic nerve activity (P < 0.05) equally in both groups without affecting the burst amplitude–duration integral (i.e. area under the curve). PVN inhibition did not affect the amplitude of the inspiratory peak, expiratory trough or expiratory peak of sSNA in either group, but reduced cardiac rhythmic sSNA in DH rats only (P < 0.001). The latter was largely reversed by inflating an aortic cuff to restore MAP (n = 5), suggesting that the muscimol-induced reduction of cardiac rhythmic sSNA in DH rats was an indirect effect of reducing MAP and thus arterial baroreceptor input. We conclude that MAP is largely maintained in anaesthetized DH rats by a PVN-driven component of sSNA that is neither respiratory nor cardiac rhythmic. PMID:24973410

  4. Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways

    PubMed Central

    Knuckles, Travis L.; Yi, Jinghai; Frazer, David G.; Leonard, Howard D.; Chen, Bean T.; Castranova, Vince; Nurkiewicz, Timothy R.

    2016-01-01

    The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, the biological effects of nanoparticle inhalation are poorly understood. Rats were exposed to nanosized titanium dioxide aerosols (10 µg lung burden); at 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. Nanoparticle exposure did not alter perivascular nerve stimulation (PVNS)-induced arteriolar constriction under normal conditions; however, adrenergic receptor inhibition revealed a more robust effect. Nanoparticle inhalation reduced arteriolar dilation in response to active hyperaemia (AH). In both PVNS and AH experiments, nitric oxide synthase (NOS) inhibition affected only controls. Whereas cyclooxygenase (COX) inhibition only attenuated AH-induced arteriolar dilation in nanoparticle-exposed animals. This group displayed an enhanced U46619 constriction and attenuated iloprost-induced dilation. Collectively, these studies indicate that nanoparticle exposure reduces microvascular NO bioavailability and alters COX-mediated vasoreactivity. Furthermore, the enhanced adrenergic receptor sensitivity suggests an augmented sympathetic responsiveness. PMID:21830860

  5. 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.

  6. Effect of the sympathetic nervous system co-transmitters ATP and norepinephrine on thermoregulatory response to cooling

    PubMed Central

    Kozyreva, Tamara V; Meyta, Ekaterina S; Khramova, Galina M

    2015-01-01

    The existence of co-transmitters of the sympathetic nervous system norepinephrine (NE) and ATP implies variations in the neuromodulator mechanisms of physiological processes. The role of ATP, as a transmitter of the peripheral part of sympathetic nervous system in the formation of thermoregulatory response is not clear. Whether ATP modulates any parameters of thermoregulatory response to cold; if yes, whether co-transmitters of sympathetic nervous system ATP and NE differently modulate thermoregulatory response and on which parameters of cold-defense response the influence of ATP is more pronounced. Experiments were carried out on rats. ATP (10−6), NE (10−3), and their mixture introduced iontophoretically into skin. Their effects on thermoregulatory parameters (temperature parameters, total oxygen consumption, carbon dioxide release, muscle activity, respiratory coefficient) were studied in thermoneutral conditions (without cold load) and under the cooling. In thermoneutral conditions both ATP and NE enhance total metabolism through increase in metabolic rate of lipids, NE effect being more expressed. It was shown that ATP and NE influence predominantly on the different components of the metabolic response to cold. ATP affects to the greatest extent on cold muscular thermogenesis by increasing shivering almost twofold and lowering its initiation temperature thresholds, whereas NE mainly promotes increase in non-shivering thermogenesis. When introducing the mixture of these biological substances the effect of NE is more expressed and the ATP effect is weakened. The obtained results allow to suggest that in vivo the NE effects can be more expressed when the sympathetic nervous system is stimulated by cold. Thus, NE and ATP being co-transmitters and predominantly acting on the different processes of cold thermogenesis (ATP on shivering and NE on non-shivering) may organize the certain sequence of cold defense responses.

  7. Effect of crocin on oxidative stress in recovery from single bout of swimming exercise in rats.

    PubMed

    Altinoz, Eyup; Ozmen, Tarık; Oner, Zulal; Elbe, Hulya; Erdemli, Mehmet E; Bag, Harika G

    2016-01-01

    Physical exercise could cause muscle and tissue damage due to increase in the formation of free oxygen radicals during exercise. The aim of the present study was to investigate the effect of crocin on parameters associated with oxidative stress in recovery from acute swimming exercise in rats. Rats were divided into eight groups; Normal Control (NC: untreated and did not swim), Crocin Control (CC: received crocin and did not swim), Exercise-1 (Exe-1: untreated and swam), Exercise-24 (Exe-24: untreated and swam), Exercise-48 (Exe-48: untreated and swam), Exercise+Crocin-1 (Exe-Cro-1: received crocin and swam), Exercise+Crocin-24 (Exe-Cro-24: received crocin and swam), Exercise+Crocin-48 (Exe-Cro-48: received crocin and swam). AST, ALP, LDH, CK, XO enzymes levels increased after swimming in untreated and crocin-treated groups, but there was a less increase in crocin-treated groups. The highest MDA levels in serum were determined in Exe-1 compared with all other groups. There was significant difference between control and exercise groups in MDA level (p = 0.033). In contrast, there was significant difference between control and exercise groups in GSH level (p < 0.001). In addition, crocin given to swimming rats significantly increased GSH levels (p < 0.05) and decreased MDA levels when compared with untreated exercise groups. In conclusion, crocin is able to protect liver and skeletal muscle tissue against exercise-induced oxidative damage by preventing reactive oxygen species (ROS) production. PMID:26001290

  8. Optimized sympathetic cooling of atomic mixtures via fast adiabatic strategies

    SciTech Connect

    Choi, Stephen; Sundaram, Bala; Onofrio, Roberto

    2011-11-15

    We discuss fast frictionless cooling techniques in the framework of sympathetic cooling of cold atomic mixtures. It is argued that optimal cooling of an atomic species--in which the deepest quantum degeneracy regime is achieved--may be obtained by means of sympathetic cooling with another species whose trapping frequency is dynamically changed to maintain constancy of the Lewis-Riesenfeld adiabatic invariant. Advantages and limitations of this cooling strategy are discussed, with particular regard to the possibility of cooling Fermi gases to a deeper degenerate regime.

  9. Sympathetic nervous system regulation of the tumour microenvironment

    PubMed Central

    Cole, Steven W.; Nagaraja, Archana S.; Lutgendorf, Susan K.; Green, Paige A.; Sood, Anil K.

    2016-01-01

    The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programs that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition, and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and hematopoietic differentiation programs. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacologic strategies to inhibit cancer progression in vivo. PMID:26299593

  10. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    PubMed Central

    Kim, Jinhee; Lee, Jongcheol; Kim, Sungchul

    2015-01-01

    Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur). Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD) rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018). Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence. PMID:26392913

  11. Precocious gut maturation and immune cell expansion by single dose feeding the lectin phytohaemagglutinin to suckling rats.

    PubMed

    Prykhod'ko, Olena; Fed'kiv, Olexandr; Linderoth, Ann; Pierzynowski, Stefan G; Weström, Björn R

    2009-03-01

    The dietary lectin phytohaemagglutinin (PHA) induces gut growth and precocious maturation in suckling rats after mucosal binding. The present study investigated the dose range in which PHA provokes gut maturation and if it coincided with immune activation. Suckling rats, aged 14 d, were orogastrically fed a single increasing dose of PHA: 0 (control), 2, 10, 50 or 250 microg/g body weight (BW) in saline. The effect on gut, lymphoid organs and appearance of CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cells in the small-intestinal mucosa was studied at 12 h (acute) and 3 d (late phase) after treatment. The low PHA doses (2 and 10 microg/g BW) induced intestinal hyperplasia without mucosal disarrangement but did not provoke gut maturation. Only the high PHA doses (50 and 250 microg/g BW) temporarily disturbed the intestinal mucosa with villi shortening and decrease in disaccharidase activities, and later after 3 d provoked precocious maturation, resulting in an increase in maltase and sucrase activities and decrease in lactase activity and disappearance of the fetal vacuolated enterocytes in the distal small intestine. Exposure to the high, but not to the low, PHA doses increased the number of mucosal CD19+ and CD3+ cells in the small intestine after 12 h, a finding also observed in untreated weaned rats aged 21-28 d. In conclusion, there was a dose-related effect of PHA on gastrointestinal growth and precocious maturation that coincided with a rapid expansion of mucosal B- and T-lymphocytes, indicating a possible involvement of the immune system in this process. PMID:18644165

  12. 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. PMID:24609799

  13. Usefulness of galvanic skin reflex monitor in CT-guided thoracic sympathetic blockade for palmar hyperhidrosis.

    PubMed

    Uchino, Hiroyuki; Sasaki, Seiichi; Miura, Hitoshi; Hirabayashi, Go; Nishiyama, Takahisa; Ohta, Takashi; Ishii, Nagao; Ito, Tatsushi

    2007-01-01

    Computed tomography (CT)-guided thoracic sympathetic blockade with ethanol was performed while monitoring sympathetic nerve activity, with an alternating current (AC) galvanic skin reflex (GSR) monitor, in a patient with palmar hyperhidrosis in whom endoscopic thoracic sympathectomy was impossible because of pleural adhesion. Sweating was suppressed after the thoracic sympathetic blockade, and the monitor showed a significant increase in skin resistance. The effect of sympathetic blockade could be evaluated directly and in real time using a GSR monitor. PMID:17680195

  14. A single dose of S-ketamine induces long-term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation.

    PubMed

    Réus, Gislaine Z; Carlessi, Anelise S; Titus, Stephanie E; Abelaira, Helena M; Ignácio, Zuleide M; da Luz, Jaine R; Matias, Beatriz I; Bruchchen, Livia; Florentino, Drielly; Vieira, Andriele; Petronilho, Fabricia; Quevedo, João

    2015-11-01

    Ketamine, an antagonist of N-methyl-d-aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived+saline; nondeprived+S-ketamine (15 mg/kg); deprived+saline; deprived+S-ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive-like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive-like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long-term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long-term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. PMID:25728399

  15. In vivo estimation of optical properties of rat liver using single-reflectance fiber probe during ischemia and reperfusion

    NASA Astrophysics Data System (ADS)

    Akter, Sharmin; Tanabe, Tomoki; Maejima, Satoshi; Kawauchi, Satoko; Sato, Shunichi; Hinoki, Akinari; Aosasa, Suefumi; Yamamoto, Junji; Nishidate, Izumi

    2016-04-01

    To quantify the changes in optical properties of in vivo rat liver tissue, we applied diffuse reflectance spectroscopy (DRS) system using single-reflectance fiber probe during ischemia and reperfusion evoked by hepatic portal occlusion (hepatic artery, portal vein and bile duct). Changes in the reduced scattering coefficient μ s', the absorption coefficient μ a, the tissue oxygen saturation StO2, and the oxidation of heme aa3 in cytochrome c oxidase (C cO) OHaa3 of in vivo rat liver (n = 6) were evaluated. Heme aa3 in C cO were significantly reduced (P < 0.05) during ischemia, which indicates a sign of mitochondrial energy failure induced by oxygen insufficiency of liver tissue. We found that OHaa3 obtained from the proposed method was unchanged immediately after the onset of ischemia and started gradually decreasing at 2 min after the onset of ischemia. Difference in the time course between OHaa3 and the conventional ratio metric analysis with μ a(605)/ μ a(620) reported in literature demonstrates that the proposed method is effective in reduction of optical cross talk between hemoglobin and heme aa3. Our results suggest that DRS technique is applicable and useful for assessing in vivo tissue viability and hemodynamics in liver intraoperatively.

  16. Effects of Single Exposure of Sodium Fluoride on Lipid Peroxidation and Antioxidant Enzymes in Salivary Glands of Rats

    PubMed Central

    Yamaguti, Paula Mochidome; Simões, Alyne; Ganzerla, Emily; Souza, Douglas Nesadal; Nogueira, Fernando Neves; Nicolau, José

    2013-01-01

    Many studies suggest that fluoride exposure can inhibit the activity of various enzymes and can generate free radicals, which interfere with antioxidant defence mechanisms in living systems. To further the understanding of this issue, this present study examined the effects of low-dose fluoride treatment on the activity of enzymatic antioxidant superoxide dismutase (SOD) and catalase (CAT), as well as the levels of lipid peroxidation (LPO) in the parotid (PA) and submandibular (SM) salivary glands of rats. Rats were injected with a single dose of sodium fluoride (NaF) (15 mg F−/kg b.w.) then euthanized at various time intervals up to 24 hours (h) following exposure. NaF exposure did not cause significant differences in SOD or CAT activity or LPO levels in PA glands compared to control. Conversely, SM glands presented increased SOD activity after 3 h and decreased SOD activity after 1, 12, and 24 h, while LPO was increased after 6, 12, and 24 h of the NaF injection. There were no significant differences in the CAT activity in the groups studied. Our results demonstrated that NaF intoxication caused oxidative stress in salivary glands few hours after administration. These changes were more pronounced in SM than in PA gland. PMID:23738039

  17. A pharmacokinetic study of patchouli alcohol after a single oral administration of patchouli alcohol or patchouli oil in rats.

    PubMed

    Zhang, Ruoqi; Yan, Peiao; Li, Yunxia; Xiong, Liang; Gong, Xiaohong; Peng, Cheng

    2016-08-01

    Pogostemonis herba is used in traditional Chinese medicine to remove dampness, relieve sunstroke, stop vomiting and increase appetite. Patchouli alcohol, an ingredient in pogostemonis herba, has the potential to treat inflammation as well as bacterial and fungal infections. The essential oil of pogostemonis herba (patchouli oil) is commonly given orally in clinical settings; however, no pharmacokinetic studies have examined its oral administration. The goal of this study was to investigate the pharmacokinetic behavior of patchouli alcohol following single-dose oral administration in rats; the influence of other patchouli oil components on the pharmacokinetic profile of patchouli alcohol was also examined. In this study, a simple and selective GC/MS method was developed and validated to measure the level of patchouli alcohol in rat plasma. The study revealed that the pharmacokinetics profile was linear in both the patchouli alcohol and patchouli oil groups. The C max and AUC0-t of patchouli alcohol were greater in all three doses of patchouli alcohol compared to corresponding patchouli oil doses. Additionally, the T max values were significantly greater in the patchouli oil group. These results suggest that the other ingredients in patchouli oil influence the pharmacokinetic behavior of patchouli alcohol during its absorption. The results provide a meaningful basis for evaluating the clinical application of patchouli oil and patchouli alcohol. PMID:25753831

  18. Behavioral changes over time in post-traumatic stress disorder: Insights from a rat model of single prolonged stress.

    PubMed

    Wu, Zhuoyun; Tian, Qing; Li, Feng; Gao, Junqiao; Liu, Yan; Mao, Meng; Liu, Jing; Wang, Shuyan; Li, Genmao; Ge, Dongyu; Mao, Yingqiu; Zhang, Wei; Liu, Zhaolan; Song, Yuehan

    2016-03-01

    Post-traumatic stress disorder (PTSD) is manifested as a persistent mental and emotional condition after potentially life-threatening events. Different animal models of PTSD have been developed for neuro-pathophysiology and pharmacological evaluations. A single prolonged stress (SPS) induced animal model has demonstrated to result in specific neuro-endocrinological dysregulation, and behavior abnormalities observed in PTSD. However, animal studies of PTSD have mostly been performed at one time point after SPS exposure. To better understand the development of PTSD-like behaviors in the SPS animal model, and to identify an optimal period of study, we examined depressive behavior, anxiety-like behavior, physical activity and body weight in SPS model rats for two weeks. Our results confirmed the SPS-induced PTSD-like behavior and physical activity observed in previous studies, and indicated that the most pronounced symptomatic behavior changes were observed on day 1 and 7 after SPS exposure, which may involve stress-induced acute hormone changes and unclear secondary neurobiological changes, respectively. These results provide a solid basis for further investigation into the neuro-pathophysiology of or neuropharmacology for PTSD using the SPS rat model. However, for chronic (pharmacological) studies longer than 7 days, a prolonged PTSD animal model should be developed, perhaps using enhanced stimulation. PMID:26772783

  19. Comparative Metabolism Studies of Hexabromocyclododecane (HBCD) Diastereomers in Male Rats Following a Single Oral Dose.

    PubMed

    Hakk, Heldur

    2016-01-01

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively accounting for 42% of dose for α-HBCD, 59% for ß-HBCD, and 53% for γ-HBCD. Urine was also an important route of HBCD excretion, accounting for 13% of dose for α-HBCD, 30% for ß-HBCD, and 21% for γ-HBCD. Total metabolism of HBCD diastereomers followed the rank order ß > γ > α, and was >65% of that administered. The metabolites formed were distinct in male rats: α-HBCD did not debrominate or stereoisomerize, but formed two hydroxylated metabolites; ß- and γ-HBCD were both extensively metabolized via pathways of stereoisomerization, oxidation, dehydrogenation, reductive debromination, and ring opening. ß-HBCD was biotransformed to two mercapturic acid pathway metabolites. The metabolites of ß- and γ-HBCD were largely distinct, and could possibly be used as markers of exposure. These isomer-specific data suggest that α-HBCD would be the most dominant HBCD diastereomer in biological tissues because it was metabolized to the lowest degree and also accumulated from the stereoisomerization of the β- and γ- diastereomers. PMID:26629593

  20. Juxtacellular Monitoring and Localization of Single Neurons within Sub-cortical Brain Structures of Alert, Head-restrained Rats.

    PubMed

    Moore, Jeffrey D; Deschênes, Martin; Kleinfeld, David

    2015-01-01

    There are a variety of techniques to monitor extracellular activity of single neuronal units. However, monitoring this activity from deep brain structures in behaving animals remains a technical challenge, especially if the structures must be targeted stereotaxically. This protocol describes convenient surgical and electrophysiological techniques that maintain the animal's head in the stereotaxic plane and unambiguously isolate the spiking activity of single neurons. The protocol combines head restraint of alert rodents, juxtacellular monitoring with micropipette electrodes, and iontophoretic dye injection to identify the neuron location in post-hoc histology. While each of these techniques is in itself well-established, the protocol focuses on the specifics of their combined use in a single experiment. These neurophysiological and neuroanatomical techniques are combined with behavioral monitoring. In the present example, the combined techniques are used to determine how self-generated vibrissa movements are encoded in the activity of neurons within the somatosensory thalamus. More generally, it is straightforward to adapt this protocol to monitor neuronal activity in conjunction with a variety of behavioral tasks in rats, mice, and other animals. Critically, the combination of these methods allows the experimenter to directly relate anatomically-identified neurophysiological signals to behavior. PMID:25938559

  1. Age-dependent differences in the strength and persistence of psychostimulant-induced conditioned activity in rats: effects of a single environment-cocaine pairing.

    PubMed

    McDougall, Sanders A; Pipkin, Joseph A; Der-Ghazarian, Taleen; Cortez, Anthony M; Gutierrez, Arnold; Lee, Ryan J; Carbajal, Sandra; Mohd-Yusof, Alena

    2014-10-01

    The aim of the present study was to determine the strength and persistence of cocaine-induced conditioned activity in young and adult rats. A one-trial protocol has proven useful for studying the ontogeny of psychostimulant-induced behavioral sensitization; therefore, a similar procedure was used to examine conditioned activity. On postnatal day (PD) 19 or PD 80, rats were injected with saline or cocaine in either a novel test chamber or the home cage. After various drug abstinence intervals (1-21 days), rats were injected with saline and returned to the test chamber, where conditioned activity was assessed. In a separate experiment, we examined whether cocaine-induced conditioned activity was a consequence of Pavlovian conditioning or a failure to habituate to the test environment. The results indicated that adult rats showed strong one-trial conditioned activity that persisted for at least 21 days, whereas young rats did not show a conditioned locomotor response. The conditioned activity shown by adult rats did not result from a failure to habituate to the cocaine-paired environment. These results indicate that cocaine-paired contextual stimuli differentially affect behavior depending on the age of the animal. The data obtained from adult rats have potential translational relevance for humans because a single environment-drug pairing caused long-term alterations in behavior. PMID:25171082

  2. Kinetics of selected di-n-butyl phthalate metabolites and fetal testosterone following repeated and single administration in pregnant rats.

    PubMed

    Clewell, Rebecca A; Kremer, John J; Williams, Carla C; Campbell, Jerry L; Sochaski, Mark A; Andersen, Melvin E; Borghoff, Susan J

    2009-01-01

    Human exposure to phthalic acid diesters occurs through a variety of pathways as a result of their widespread use in consumer products and plastics. Repeated doses of di-n-butyl phthalate (DBP) from gestation day (GD) 12 to 19 disrupt testosterone synthesis and male sexual development in the fetal rat. Currently little is known about the disposition of DBP metabolites, such as monobutyl phthalate (MBP) and its glucuronide conjugate (MBP-G), during gestation after repeated exposure to DBP. In order to gain a better understanding of the effect of repeated dosing on maternal and fetal metabolism and distribution, pregnant Sprague-Dawley rats were given a single dose of 500 mg/kg DBP on GD 19 or daily doses of 50, 100, and 500 mg/(kg day) from GD 12 to 19 via corn oil gavage. Dose-response evaluation revealed a non-linear increase in maternal and fetal plasma concentrations of MBP. Maternal and fetal MBP levels were slightly lower in animals after 8 days of dosing at 500 mg/(kg day). Fetal plasma MBP levels closely followed maternal plasma, while the appearance and elimination of MBP-G in fetal plasma were significantly delayed. MBP-G accumulated over time in the amniotic fluid. Inhibition of testosterone was rapid in fetal testes when exposed to DBP (500 mg/(kg day)) on GD 19. Within 24h, the level of inhibition in the fetus was similar between animals exposed to a single or multiple daily doses of 500 mg/(kg day). Examination of testosterone time-course data indicates a rapid recovery to normal levels within 24h post-dosing at DBP doses of 50 and 100 mg/(kg day), with a rebound to higher than normal concentrations at later time-points. MBP kinetics in fetal testes allows direct comparison of active metabolite concentrations and testosterone response in the fetal testes. PMID:19010379

  3. Dose Optimization for Single Intradiscal Administration of the Tumor Necrosis Factor-α Inhibitor, Etanercept, in Rat Disc Injury Models

    PubMed Central

    Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Study Design Experimental animal study. Purpose We aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury. Overview of Literature The pain-related peptide expression was suppressed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner. Methods The neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 µg, 100 µg, or 1,000 µg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups. Results There were no significant differences between the puncture+saline group and the puncture+10-µg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner (p <0.05). Conclusions When a low dose of the TNF-α inhibitor (10 µg of etanercept) was directly administered to the rat intervertebral disc in the rat model of degenerative intervertebral disc from injury, no suppressive effect on the pain-related peptide expression was observed. However, when a higher dose of etanercept (100 µg and 1,000 µg) was administered, the pain-related peptide expression was suppressed in a dose-dependent manner. PMID:27559439

  4. Autonomic mechanisms underpinning the stress response in borderline hypertensive rats

    PubMed Central

    Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina

    2011-01-01

    This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors. PMID:21421701

  5. Effects of endotoxin on monoamine metabolism in the rat.

    NASA Technical Reports Server (NTRS)

    Pohorecky, L. A.; Wurtman, R. J.; Taam, D.; Fine, J.

    1972-01-01

    Examination of effects of administered endotoxin on catecholamine metabolism in the rat brain, sympathetic neurons, and adrenal medulla. It is found that endotoxin, administered intraperitoneally, lowers the norepinephrine content in peripheral sympathetic neurons and the brain, and the catecholamine content in the adrenal medulla. It also accelerates the disappearance of H3-norepinephrine from all these tissues. It is therefore suggested that the effects of endotoxin on body temperature may be mediated in part by central non-adrenergic neurons.

  6. Animal aging and regulation of sympathetic nerve discharge

    PubMed Central

    2010-01-01

    Studies completed in human subjects have made seminal contributions to understanding the effects of age on sympathetic nervous system (SNS) regulation. Numerous experimental constraints limit the design of studies involving human subjects; therefore, completion of studies in animal models of aging would be expected to provide additional insight regarding mechanisms mediating age-related changes in sympathetic nerve discharge (SND) regulation. The present review assesses the current state of the literature regarding contributions from animal studies on the effects of advancing age on SND regulation, focusing primarily on studies that have used direct recordings of sympathetic nerve outflow. Few studies using direct SND recordings have been completed in animal models of aging, regardless of the fundamental component of SND regulation reviewed (basal levels, acute responsiveness, relationships between the discharges in sympathetic nerves, central neural regulation). SNS responsiveness to various acute stressors is altered in aged compared with young animals; however, mechanisms remain virtually unexplored. There is a marked dearth of studies that have used central neural microinjection techniques in conjunction with SND recordings in aged animals, making it difficult to develop an evidence-based framework regarding potential age-associated effects on central regulation of SND. Determination of age-related changes in mechanisms regulating SND is important for understanding relationships between chronic disease development and changes in SNS function; however, this can only be achieved by substantially extending the current knowledge base regarding the effects of age on SND regulation in animal studies. PMID:20651223

  7. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    SciTech Connect

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J. )

    1990-05-01

    Sites of uptake, storage, and metabolism of ({sup 18}F)fluorodopamine and excretion of ({sup 18}F)fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of ({sup 18}F)-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of ({sup 18}F)fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.

  8. Axillary Brachial Plexus Blockade for the Reflex Sympathetic Dystrophy Syndrome.

    ERIC Educational Resources Information Center

    Ribbers, G. M.; Geurts, A. C. H.; Rijken, R. A. J.; Kerkkamp, H. E. M.

    1997-01-01

    Reflex sympathetic dystrophy syndrome (RSD) is a neurogenic pain syndrome characterized by pain, vasomotor and dystrophic changes, and often motor impairments. This study evaluated the effectiveness of brachial plexus blockade with local anaesthetic drugs as a treatment for this condition. Three patients responded well; three did not. (DB)

  9. 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. PMID:26381017

  10. 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.

  11. Forearm sympathetic withdrawal and vasodilatation during mental stress in humans.

    PubMed

    Halliwill, J R; Lawler, L A; Eickhoff, T J; Dietz, N M; Nauss, L A; Joyner, M J

    1997-10-01

    1. In humans, mental stress elicits vasodilatation in the muscle vascular beds of the forearm that may be neurally mediated. We sought to determine the extent to which this vasodilatation is due to sympathetic withdrawal, active neurogenic vasodilatation, or beta-adrenergically mediated vasodilatation. 2. We simultaneously measured forearm blood flow and muscle sympathetic nerve traffic to the forearm during mental stress in humans. In a second study, we measured forearm blood flow responses to mental stress after selective blockade of alpha-adrenergic neurotransmission in one forearm. In a final study, we measured forearm blood flow responses to mental stress after unilateral anaesthetic blockade of the stellate ganglion, alone or in combination with selective beta-adrenergic receptor blockade of the forearm. 3. During mental stress, muscle sympathetic nerve activity decreased from 5113 +/- 788 to 1509 +/- 494 total integrated activity min-1 (P < 0.05) and forearm vascular resistance decreased from 96 +/- 29 to 33 +/- 7 mmHg (dl of tissue) min ml-1 (P < 0.05). Considerable vasodilation was still elicited by mental stress after selective blockade of alpha-adrenergic neurotransmission. Vasodilatation also occurred during mental stress after stellate ganglion blockade. This dilatation was reduced by selective blockade of beta-adrenergic receptors in the forearm. 4. Our results support a role for both sympathetic withdrawal and beta-adrenergic vasodilatation as the major causes of the forearm vasodilatation during mental stress in humans. PMID:9350631

  12. Forearm sympathetic withdrawal and vasodilatation during mental stress in humans.

    PubMed Central

    Halliwill, J R; Lawler, L A; Eickhoff, T J; Dietz, N M; Nauss, L A; Joyner, M J

    1997-01-01

    1. In humans, mental stress elicits vasodilatation in the muscle vascular beds of the forearm that may be neurally mediated. We sought to determine the extent to which this vasodilatation is due to sympathetic withdrawal, active neurogenic vasodilatation, or beta-adrenergically mediated vasodilatation. 2. We simultaneously measured forearm blood flow and muscle sympathetic nerve traffic to the forearm during mental stress in humans. In a second study, we measured forearm blood flow responses to mental stress after selective blockade of alpha-adrenergic neurotransmission in one forearm. In a final study, we measured forearm blood flow responses to mental stress after unilateral anaesthetic blockade of the stellate ganglion, alone or in combination with selective beta-adrenergic receptor blockade of the forearm. 3. During mental stress, muscle sympathetic nerve activity decreased from 5113 +/- 788 to 1509 +/- 494 total integrated activity min-1 (P < 0.05) and forearm vascular resistance decreased from 96 +/- 29 to 33 +/- 7 mmHg (dl of tissue) min ml-1 (P < 0.05). Considerable vasodilation was still elicited by mental stress after selective blockade of alpha-adrenergic neurotransmission. Vasodilatation also occurred during mental stress after stellate ganglion blockade. This dilatation was reduced by selective blockade of beta-adrenergic receptors in the forearm. 4. Our results support a role for both sympathetic withdrawal and beta-adrenergic vasodilatation as the major causes of the forearm vasodilatation during mental stress in humans. PMID:9350631

  13. 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

  14. Essential role of Gata transcription factors in sympathetic neuron development.

    PubMed

    Tsarovina, Konstantina; Pattyn, Alexandre; Stubbusch, Jutta; Müller, Frank; van der Wees, Jacqueline; Schneider, Carolin; Brunet, Jean-Francois; Rohrer, Hermann

    2004-10-01

    Sympathetic neurons are specified during their development from neural crest precursors by a network of crossregulatory transcription factors, which includes Mash1, Phox2b, Hand2 and Phox2a. Here, we have studied the function of Gata2 and Gata3 zinc-finger transcription factors in autonomic neuron development. In the chick, Gata2 but not Gata3 is expressed in developing sympathetic precursor cells. Gata2 expression starts after Mash1, Phox2b, Hand2 and Phox2a expression, but before the onset of the noradrenergic marker genes Th and Dbh, and is maintained throughout development. Gata2 expression is affected in the chick embryo by Bmp gain- and loss-of-function experiments, and by overexpression of Phox2b, Phox2a, Hand2 and Mash1. Together with the lack of Gata2/3 expression in Phox2b knockout mice, these results characterize Gata2 as member of the Bmp-induced cluster of transcription factors. Loss-of-function experiments resulted in a strong reduction in the size of the sympathetic chain and in decreased Th expression. Ectopic expression of Gata2 in chick neural crest precursors elicited the generation of neurons with a non-autonomic, Th-negative phenotype. This implies a function for Gata factors in autonomic neuron differentiation, which, however, depends on co-regulators present in the sympathetic lineage. The present data establish Gata2 and Gata3 in the chick and mouse, respectively, as essential members of the transcription factor network controlling sympathetic neuron development. PMID:15329349

  15. Effects produced by single and repeated dosages of Fipronil on the EEG of Long Evans Rats

    EPA Science Inventory

    We have previously reported that various classes of pesticides have different effects on the non- stimulus driven EEG after acute treatment, including fipronil (25 or 50 mg/kg) (Lyke et a!., Toxicologist, 2010, 2011, 2012, 2013). In this study, we compared the effects of single a...

  16. Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

    PubMed Central

    Neth, Katharina; Lucio, Marianna; Walker, Alesia; Zorn, Julia; Schmitt-Kopplin, Philippe; Michalke, Bernhard

    2015-01-01

    Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography—inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization—ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism. PMID:26383269

  17. Single amino acid sequence polymorphisms in rat cardiac troponin revealed by top-down tandem mass spectrometry.

    PubMed

    Sancho Solis, Raquel; Ge, Ying; Walker, Jeffery W

    2008-01-01

    Heterotrimeric cardiac troponin (cTn) is a critical component of the thin filament regulatory complex in cardiac muscle. Two of the three subunits, cTnI and cTnT, are subject to post-translational modifications such as proteolysis and phosphorylation, but linking modification patterns to function remains a major challenge. To obtain a global view of the biochemical state of cTn in native tissue, we performed high resolution top-down mass spectrometry of cTn heterotrimers from healthy adult rat hearts. cTn heterotrimers were affinity purified, desalted and then directly subjected to mass spectrometry using a 7 Tesla Thermo LTQ-FT-ICR instrument equipped with an ESI source. Molecular ions for N-terminally processed and acetylated cTnI and cTnT were readily detected as were other post-translationally modified forms of these proteins. cTnI was phosphorylated with a distribution of un-, mono- and bisphosphorylated forms of 41 +/- 3%, 46 +/- 1%, 13 +/- 3%, respectively. cTnT was predominantly monophosphorylated and partially proteolyzed at the Glu(29)-Pro(30) peptide bond. Also observed in high resolution spectra were 'shadow' peaks of similar intensity to 'parent' peaks exhibiting masses of cTnI+16 Da and cTnT+128 Da, subsequently shown by tandem mass spectrometry (MS/MS) to be single amino acid polymorphisms. Intact and protease-digested cTn subunits were fragmented by electron capture dissociation or collision activated dissociation to localize an Ala/Ser polymorphism at residue 7 of cTnI. Similar analysis of cTnT localized an additional Gln within a three residue alternative splice site beginning at residue 192. Besides being able to provide unique insights into the global state of post-translational modification of cTn subunits, high resolution top-down mass spectrometry readily revealed naturally occurring single amino acid sequence variants including a genetic polymorphism at residue 7 in cTnI, and an alternative splice isoform that affects a putative hinge region

  18. GABA mechanisms of the nucleus of the solitary tract regulates the cardiovascular and sympathetic effects of moxonidine.

    PubMed

    Alves, Thales B; Totola, Leonardo T; Takakura, Ana C; Colombari, Eduardo; Moreira, Thiago S

    2016-01-01

    The antihypertensive drugs moxonidine and clonidine are α2-adrenoceptor and imidazoline (I1) agonists. Previous results from our laboratory have shown that moxonidine can act in the commissural nucleus of the solitary tract (commNTS). In addition, some studies have shown that GABA or glutamate receptor blockade in the RVLM blunted the hypotension produced by these antihypertensive agents in spontaneously hypertensive rats. Therefore, in the present study we verify whether the cardiovascular and sympathetic effects produced by moxonidine in the commNTS are dependent on GABAergic or glutamatergic mechanisms. Mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (sSNA) were recorded in urethane-anesthetized, and artificially-ventilated male Wistar rats (250-350 g). Injection of the GABAA antagonist bicuculline (25 pmol/50 nL) into the commNTS reduced the hypotension as well as the sympathoinhibition elicited by moxonidine. Prior injection of the glutamate receptor antagonist kynurenic acid (2.5 nmol/50 nL) into the commNTS was not effective in reducing the hypotension and sympathoinhibition elicited by moxonidine. Therefore, we conclude that the hypotensive and sympathoinhibitory effects elicited by microinjection of moxonidine into the commNTS are dependent on GABA receptors, but not ionotropic glutamate receptors. PMID:26633249

  19. Role of the renin-angiotensin system in the regulation of intestinal blood flow and sympathetic neurotransmission

    SciTech Connect

    Suvannapura, A.

    1988-01-01

    The aims of the present studies were (1) to determine if endogenous angiotensin II (Ang II) plays a role in the local control of mesenteric blood flow (MBF) following volume depletion in anesthetized dogs, and (2) to investigate the mechanism(s) of actions of Ang II on the facilitation of sympathetic neurotransmission in the rate jejunum. To investigate the role of endogenous Ang II in the control of MBF, a dose of an antagonist of Ang II, saralasin, that has effects mainly localized to the mesenteric circulation was determined. The data demonstrated that blockage of actions of Ang II in the mesenteric circulation resulted in a decrease in intestinal vasoconstriction which occurred following acute hypotensive hemorrhage. The effect of Ang II on the uptake and release of norepinephrine from sympathetic nerve endings in the rat jejunum was investigated. The uptake of norepinephrine in rat jejunum was determined by incubating jejunal slices in Krebs buffer containing 0.01 {mu}M {sup 3}H-norepinephrine. The accumulation of label in the tissue after 10 min incubation was determined by liquid scintillation spectrometry. Intracellular uptake of {sup 3}H-norepinephrine was calculated and shown to be an active process.

  20. Acute Phase Pulmonary Responses to a Single Intratracheal Spray Instillation of Magnetite (Fe3O4) Nanoparticles in Fischer 344 Rats

    PubMed Central

    Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Ogata, Akio; Nakae, Dai

    2012-01-01

    Iron nanomaterials are of considerable interest for application to nanotechnology-related fields including environmental catalysis, biomedical imaging, drug delivery and hyperthermia, because of their superparamagnetic characteristics and high catalytic abilities. However, information about potential risks of iron nanomaterials is limited. The present study assessed pulmonary responses to a single intratracheal spray instillation of triiron tetraoxide nanoparticles (magnetite) in rats. Ten-week-old male and female Fischer 344 rats (n=5/group) were exposed to a single intratracheal spray instillation of 0 (vehicle), 5.0, 15.0 or 45.0 mg/kg body weight (BW) of magnetite. After 14 days, the rats were sacrificed, and biological consequences were investigated. The lung weights of the 15.0 and 45.0 mg/kg BW male and female groups were significantly higher than those of the control groups. The lungs of treated rats showed enlargement and black patches originating from the color of magnetite. The typical histopathological changes in the lungs of the treated rats included infiltration of macrophages phagocytosing magnetite, inflammatory cell infiltration, granuloma formation and an increase of goblet cells in the bronchial epithelium. The results clearly show that instilled magnetite causes foreign body inflammatory and granulating lesions in the lung. These pulmonary responses occur in a dose-dependent manner in association with the increase in lung weight. PMID:23345925

  1. Acute phase pulmonary responses to a single intratracheal spray instillation of magnetite (fe(3)o(4)) nanoparticles in Fischer 344 rats.

    PubMed

    Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Ogata, Akio; Nakae, Dai

    2012-12-01

    Iron nanomaterials are of considerable interest for application to nanotechnology-related fields including environmental catalysis, biomedical imaging, drug delivery and hyperthermia, because of their superparamagnetic characteristics and high catalytic abilities. However, information about potential risks of iron nanomaterials is limited. The present study assessed pulmonary responses to a single intratracheal spray instillation of triiron tetraoxide nanoparticles (magnetite) in rats. Ten-week-old male and female Fischer 344 rats (n=5/group) were exposed to a single intratracheal spray instillation of 0 (vehicle), 5.0, 15.0 or 45.0 mg/kg body weight (BW) of magnetite. After 14 days, the rats were sacrificed, and biological consequences were investigated. The lung weights of the 15.0 and 45.0 mg/kg BW male and female groups were significantly higher than those of the control groups. The lungs of treated rats showed enlargement and black patches originating from the color of magnetite. The typical histopathological changes in the lungs of the treated rats included infiltration of macrophages phagocytosing magnetite, inflammatory cell infiltration, granuloma formation and an increase of goblet cells in the bronchial epithelium. The results clearly show that instilled magnetite causes foreign body inflammatory and granulating lesions in the lung. These pulmonary responses occur in a dose-dependent manner in association with the increase in lung weight. PMID:23345925

  2. Blood Pressure Increases in OSA due to Maintained Neurovascular Sympathetic Transduction: Impact of CPAP

    PubMed Central

    Tamisier, Renaud; Tan, Can Ozan; Pepin, Jean-Louis; Levy, Patrick; Taylor, J. Andrew

    2015-01-01

    Study Objectives: To test the hypothesis that greater resting sympathetic activity in obstructive sleep apnea (OSA) syndrome would not induce a lesser sympathetic neurovascular transduction. Design: Case-controlled cohort study. Participants: 33 patients with newly diagnosed OSA without comorbidities and 14 healthy controls. Interventions: 6 months of continuous positive airway pressure (CPAP) treatment for OSA patients and follow-up for 9 healthy controls. Measurements and Results: We assessed resting sympathetic outflow and sympathetic neurovascular transduction. Sympathetic activity was directly measured (microneurography) at rest and in response to sustained isometric handgrip exercise. Neurovascular transduction was derived from the relationship of sympathetic activity and blood pressure to leg blood flow during exercise. Despite an elevated sympathetic activity of ∼50% in OSA compared to controls, neurovascular transduction was not different (i.e., absence of tachyphylaxis). After six months of CPAP, there were significant declines in diastolic pressure, averaging ∼4 mm Hg, and in sympathetic activity, averaging ∼20% with no change in transduction. Conclusions: Greater sympathetic activity in obstructive sleep apnea does not appear to be associated with lesser neurovascular transduction. Hence, elevated sympathetic outflow without lesser transduction may underlie the prevalent development of hypertension in this population that is well controlled by continuous positive airway pressure treatment. Citation: Tamisier R, Tan CO, Pepin JL, Levy P, Taylor JA. Blood pressure increases in OSA due to maintained neurovascular sympathetic transduction: impact of CPAP. SLEEP 2015;38(12):1973–1980. PMID:26039959

  3. A Multivariate Logistical Model for Identifying the Compressive Sensitivity of Single Rat Tactile Receptors as Nanobiosensors

    PubMed Central

    Bradshaw, Sam; Mason, Shelley S.; Looft, Fred J.

    2010-01-01

    Tactile sensation is a complex manifestation of mechanical stimuli applied to the skin. At the most fundamental level of the somatosensory system is the cutaneous mechanoreceptor. The objective here was to establish a framework for modeling afferent mechanoreceptor behavior as a nanoscale biosensor under dynamic compressive loads using multivariate regression techniques. A multivariate logistical model was chosen because the system contains continuous input variables and a singular binary-output variable corresponding to the nerve action potential. Subsequently, this method was used to quantify the sensitivity of ten rapidly adapting afferents from rat hairy skin due to the stimulus metrics of compressive stress, strain, their respective time derivatives, and interactions. In vitro experiments involving compressive stimulation of isolated afferents using pseudorandom and nonrepeating noise sequences were completed. An analysis of the data was performed using multivariate logistical regression producing odds ratios (ORs) as a metric associated with mechanotransduction. It was determined that cutaneous mechanoreceptors are preferentially sensitive to stress (mean ORmax = 26.10), stress rate (mean ORmax = 15.03), strain (mean ORmax = 12.01), and strain rate (mean ORmax = 7.29) typically occurring within 7.3 ms of the nerve response. As a novel approach to receptor characterization, this analytical framework was validated for the multiple-input, binary-output neural system. PMID:21197157

  4. Effects of Single Treatment of Anti-Dementia Drugs on Sleep-Wake Patterns in Rats

    PubMed Central

    Jung, Ji-Young; Roh, Mootaek; Ko, Kyung-Kyun; Jang, Hwan-Soo; Lee, Seong-Ryong; Ha, Jeoung-Hee; Jang, Il-Sung; Lee, Ho-Won; Lee, Maan-Gee

    2012-01-01

    We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30. Vibration was recorded to monitor animal activity with a vibration measuring device. Sleep-wake states such as wake (W), slow-wave sleep (S) and paradoxical or rapid eye movement sleep (P), were scored every 10 sec by an experimenter. We measured mean episode duration and number of episode to determine which factor sleep disturbance was attributed to. Donepezil and memantine showed a significant increase in total W duration and decreases in total S and P duration and delta activity. Memantine showed increases in sleep latency and motor activity. Changes of S and P duration in memantine were attributed from changes of mean episode duration. Galantamine had little effect on sleep architecture. From these results, it is showed that galantamine may be an anti-dementia drug that does not cause sleep disturbances and memantine may be a drug that causes severe sleep disturbance. PMID:22915987

  5. Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1.

    PubMed

    Newman, Zachary L; Printz, Morton P; Liu, Shihui; Crown, Devorah; Breen, Laura; Miller-Randolph, Sharmina; Flodman, Pamela; Leppla, Stephen H; Moayeri, Mahtab

    2010-05-01

    Anthrax lethal toxin (LT) is a bipartite protease-containing toxin and a key virulence determinant of Bacillus anthracis. In mice, LT causes the rapid lysis of macrophages isolated from certain inbred strains, but the correlation between murine macrophage sensitivity and mouse strain susceptibility to toxin challenge is poor. In rats, LT induces a rapid death in as little as 37 minutes through unknown mechanisms. We used a recombinant inbred (RI) rat panel of 19 strains generated from LT-sensitive and LT-resistant progenitors to map LT sensitivity in rats to a locus on chromosome 10 that includes the inflammasome NOD-like receptor (NLR) sensor, Nlrp1. This gene is the closest rat homolog of mouse Nlrp1b, which was previously shown to control murine macrophage sensitivity to LT. An absolute correlation between in vitro macrophage sensitivity to LT-induced lysis and animal susceptibility to the toxin was found for the 19 RI strains and 12 additional rat strains. Sequencing Nlrp1 from these strains identified five polymorphic alleles. Polymorphisms within the N-terminal 100 amino acids of the Nlrp1 protein were perfectly correlated with LT sensitivity. These data suggest that toxin-mediated lethality in rats as well as macrophage sensitivity in this animal model are controlled by a single locus on chromosome 10 that is likely to be the inflammasome NLR sensor, Nlrp1. PMID:20502689

  6. The functional significance of the sympathetic innervation of mucous glands in the bronchi of man.

    PubMed Central

    Pack, R J; Richardson, P S; Smith, I C; Webb, S R

    1988-01-01

    1. Pieces of human bronchi, from lung resected for carcinoma of the bronchus, were mounted in Ussing chambers and given [35S]sulphate as radiolabelled precursor of mucous glycoproteins (mucins). The release of 35S, bound to macromolecules, into the luminal half-chamber was used as an index of mucin secretion. 2. Noradrenaline, at concentrations of 1, 10 and 100 microM, was given into both halves of the Ussing chamber. At the lowest concentration, noradrenaline failed to change mucin output, but at the two higher concentrations it stimulated output. 3. In other experiments the sympathetic nerves in the bronchial wall were labelled with 5-hydroxydopamine and examined under the electron microscope. The distances between adrenergic nerve varicosities and submucosal glands were measured; some sympathetic nerve varicosities were seen within 1 microns of gland cells. 4. A simple mathematical model for the diffusion of noradrenaline was used to predict the concentrations of the transmitter likely to result at different distances from a nerve if one or more vesicles of noradrenaline were released. 5. The model predicts that the release of a single large vesicle of noradrenaline is likely to generate an effective concentration of transmitter provided that the nerve is within 1 micron of the target cell. Images Fig. 2 PMID:3253421

  7. A SINGLE HIGH DOSE OF METHAMPHETAMINE INCREASES COCAINE SELF-ADMINISTRATION BY DEPLETION OF STRIATAL DOPAMINE IN RATS

    PubMed Central

    XI, Z.-X.; KLEITZ, H. K.; DENG, X.; LADENHEIM, B.; PENG, X.-Q.; LI, X.; GARDNER, E. L.; STEIN, E. A.; CADET, J. L.

    2013-01-01

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10–20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kg×1 or 10 mg/kg/2 h×4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in “breakpoint” levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10–20 mg/kg) produced large DA release (4000%–6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  8. Adaptation of quantal content to decreased postsynaptic sensitivity at single endplates in alpha-bungarotoxin-treated rats.

    PubMed Central

    Plomp, J J; van Kempen, G T; Molenaar, P C

    1992-01-01

    1. Rats were injected once every 48 h with alpha-bungarotoxin (alpha BTX) for periods up to 6 weeks. Injections caused weakness of facial muscles which lasted about 8 h. Hemidiaphragms were dissected for biochemical and electrophysiological measurements. 2. In muscles from animals treated for 2-3 weeks with toxin, the binding of 125I-alpha BTX was reduced to 58%, and the ACh content to 81% of control values. Choline acetyltransferase activity was unchanged. ACh release evoked by 3 Hz nerve stimulation was increased to 175% of control values. 3. The use of mu-conotoxin, which specifically blocks muscle action potentials, enabled the recording of full-sized endplate potentials (EPPs) and miniature endplate potentials (MEPPs) at normal muscle membrane potentials (-70 to -80 mV). The amplitude of MEPPs was decreased to 57% in muscles from animals treated for 3 weeks with alpha BTX. The mean of the quantal contents, calculated from the ratio of the corrected EPPs and the MEPPs, was increased to 154%. 4. Within individual muscles of both alpha BTX-treated and control rats, there was an inverse relationship between the quantal content of an endplate and its MEPP amplitude. 5. The MEPP frequency of endplates from control muscles was positively correlated with the quantal content. However, this correlation was not found in alpha BTX-affected muscles. 6. Three hours after a single injection of alpha BTX the amplitude of the MEPPs was reduced to about 60% of control values but no increase of the quantal content was found. During the first few days of alpha BTX treatment the quantal content gradually increased; it reached a plateau between 20 and 30 days. 7. The results suggest the existence of an adaptive mechanism, operating at individual endplates, in which retrograde signals at the motor nerve terminals modulate ACh release when neuromuscular transmission is endangered by block of acetylcholine receptors. PMID:1302275

  9. A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats.

    PubMed

    Xi, Z-X; Kleitz, H K; Deng, X; Ladenheim, B; Peng, X-Q; Li, X; Gardner, E L; Stein, E A; Cadet, J L

    2009-06-30

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10-20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kgx1 or 10 mg/kg/2 hx4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in "break-point" levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10-20 mg/kg) produced large DA release (4000%-6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  10. Increased Nitric Oxide Bioavailability and Decreased Sympathetic Modulation Are Involved in Vascular Adjustments Induced by Low-Intensity Resistance Training.

    PubMed

    Macedo, Fabrício N; Mesquita, Thassio R R; Melo, Vitor U; Mota, Marcelo M; Silva, Tharciano L T B; Santana, Michael N; Oliveira, Larissa R; Santos, Robervan V; Miguel Dos Santos, Rodrigo; Lauton-Santos, Sandra; Santos, Marcio R V; Barreto, Andre S; Santana-Filho, Valter J

    2016-01-01

    Res