Decrease In Sympathetic Nerve Activity Research Articles

Effect of ETA receptor antagonists on cardiovascular responses induced by centrally administered sarafotoxin 6b: role of sympathetic nervous system.

The present study was carried out to investigate the cardiovascular effects of centrally administered SRT6b in saline, BQ123 and BMS182874 pretreated male Sprague-Dawley rats, using a radioactive microsphere technique. SRT6b (100 ng, ICV) produced a transient increase (40%) in blood pressure at 5 min followed by a sustained decrease (-42%) at 30 and 60 min in control rats. Total peripheral resistance and heart rate were not significantly altered. Cardiac output increased (16%) at 5 min and decreased 30 and 60 min following SRT6b administration. Central venous pressure was not affected by SRT6b. Regional blood flow and vascular resistance did not change at 5 min following administration of SRT6b. However, a significant decrease in blood flow to the brain, heart, kidneys, liver, spleen, gastrointestinal tract and mesentery and pancreas was observed 30 and 60 min following administration of SRT6b in control (saline treated) rats. Pretreatment with ETA selective receptor antagonists, BQ123 (10 micrograms, ICV) or BMS182874 (50 micrograms, ICV) significantly attenuated the pressor and depressor effects of centrally administered SRT6b. SRT6b induced decrease in blood flow was completely blocked by pretreatment with BQ123 or BMS182874. ET-1 (100 ng, ICV) produced an increase followed by a decrease similar to SRT6b. Reserpine (5 mg/kg, IP) pretreatment attenuated the cardiovascular effects of ET-1. Role of sympathetic nervous system was determined by measuring splanchnic nerve activity. SRT6b when administered in the lateral cerebral ventricle did not produce any significant effect at 5 min, however, a significant decrease in sympathetic nerve activity was observed 30 min after its administration. It is concluded that centrally administered SRT6b produces significant changes in systematic and regional blood circulation which can be completely blocked by ETA receptor antagonist. The cardiovascular effects of centrally administered SRT6b appear to be mediated through the sympathetic nervous system.

GABA b-ergic stimulation in hypothalamic pressor area induces larger sympathetic and cardiovascular depression in spontaneously hypertensive rats

To determine whether central GABA (gamma-aminobutyric acid) B receptor stimulation would affect the sympathetic and cardiovascular activities, baclofen (a GABAB receptor agonist) was injected into lateral cerebral ventricles (intracerebroventricularly, ICV) in urethane-anesthetized normotensive rats. Intracerebroventricular injections of GABAA agonist (muscimol, 1 microgram) consistently decreased blood pressure and heart rate. In contrast ICV injections of baclofen (2 micrograms) increased blood pressure (BP) and heart rate with initial transient cardiovascular depression, and these effects of baclofen were abolished by ICV pretreatment with GABAB antagonist (saclofen, 100 micrograms). To determine whether the cardiovascular effects of ICV injections were elicited by activating GABA receptors in the hypothalamus, we injected baclofen or muscimol directly into various hypothalamic areas. Baclofen (100 and 800 ng) injected into the ventromedial hypothalamus (VMH) or posterior hypothalamus (PH) of normotensive rats produced dose-related decreases in sympathetic nerve activity, blood pressure, and heart rate. These effects of baclofen were larger in VMH injections than in PH injections. The depressor responses elicited by VMH injections of baclofen were abolished by intravenous pretreatment with alpha-blocker, but unaffected by parasympathetic blocker, further indicating that the depressor responses of baclofen (VMH) were not due to parasympathetic activation, but due to peripheral sympathetic depression. Muscimol (400 ng) and baclofen (800 ng) injected into VMH produced similar amplitude of sympathetic-depressant, depressor and bradycardic responses. In contrast, BP was increased by the same dose of baclofen injected into the hypothalamic depressor area (anterior hypothalamus, AH), but was unaffected by muscimol. Final experiments were performed to determine whether these sympathetic and cardiovascular effects to hypothalamic GABAB stimulations would be altered in hypertension. In spontaneously hypertensive rats (SHR), basal BP and heart rate were already higher than in normotensive controls (Wistar-Kyoto rat, WKY). Baclofen injected into VMH reduced sympathetic nerve activity, BP, and heart rate in both groups of rats, and these effects were significantly larger in SHR than in WKY. This enhanced depressor response induced by baclofen (VMH) in SHR persisted even after sinoaortic denervation, which indicates that the enhanced depressor response is not due to reduced peripheral baroreflex sensitivity in SHR. On the other hand, baclofen injected into AH increased BP and heart rate in both WKY and SHR, but the magnitude of these responses did not differ between two groups. In summary, GABA reduces sympathetic nerve activity, BP, and heart rate through both GABAA and B receptors in VMH. The GABAB system acts on the depressor area, AH, to further regulate the cardiovascular activities. In SHR, the GABAB-ergic system in VMH but not in AH is altered, and this might contribute to the development of hypertension.

Calcium Supplementation Attenuates an Enhanced Platelet Function in Salt-Loaded Mildly Hypertensive Patients

We designed this study to evaluate the effect of low versus high calcium intake on platelet function in salt-loaded patients with mild hypertension. After a 7-day period of dietary salt restriction, 19 patients were placed on a high salt (300 mmol/d), low calcium (6.25 mmol/d) diet for 7 days; 10 of these patients were given 54 mmol/d of supplementary calcium, and 9 patients were given placebo. At the end of the low and high salt regimens, we evaluated changes in blood pressure, platelet aggregation, and the platelet release reaction measured as plasma beta-thromboglobulin and platelet factor 4 levels. With high salt intake, significant increases in mean blood pressure (P < .02), red blood cell sodium (P < .01), and platelet aggregation induced by 3 mumol/L ADP (P < .01) and by 3.0 mg/L epinephrine (P < .05) were observed in the placebo-treated patients but not in the calcium-supplemented ones. Compared with the placebo-treated patients, calcium-supplemented patients had a smaller weight gain (P < .05) but excreted more sodium and calcium (P < .01) at the end of the high salt regimen. Calcium supplementation resulted in decreases in beta-thromboglobulin (P < .05), platelet factor 4 (P < .01), and plasma and urinary excretions of norepinephrine (P < .02) during the high salt, low calcium regimen. The decrease in plasma norepinephrine correlated positively with the decreases in beta-thromboglobulin (r = .72, P < .02) and platelet factor 4 (r = .85, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of immidazoline and guanidinium compounds on the cardiovascular system

The ability of imidazoline agonists, such as moxonidine and rilmenidine, to lower blood pressure has been attributed to a central effect resulting in a decrease in peripheral sympathetic nerve activity. A similar decrease in sympathetic nerve activity to the kidney has been proposed to explain the increase in sodium excretion. The observed increase in sodium excretion following an intrarenal infusion of moxonidine or rilmenidine suggested the existence of a direct renal action. We therefore tested the hypothesis that direct renal infusions were acting at a central rather than a peripheral site. Thus, interventions which would decrease the natriuretic effects of central administered moxonidine would also block the effects of intrarenal administered moxonidine. Studies were performed in anesthetized Sprague–Dawley rats (280–320 g) which had undergone unilateral nephrectomy 7 to 10 days prior to the experiment. The interventions utilized resulted in minimal effects on blood pressure and creatinine clearance. Intracerebroventricular (icv) or intrarenal (ir) administration of moxonidine produced a significant increase in urine flow rate and sodium excretion. Intravenous (iv) prazosin was used to block the ability of the sympathetic nerves to alter sodium excretion secondary to α1-adrenoceptor stimulation. Prazosin prevented the natriuresis following icv moxonidine but only partially antagonized the effects of ir moxonidine. To determine if central imidazoline receptors mediated the effects of moxonidine, animals were pretreated with icv idazoxan. Following icv idazoxan, the effects of icv moxonidine were blocked, whereas the response to intrarenal moxonidine was only partially blocked. Peripheral (iv) administration of idazoxan blocked the actions of intrarenal moxonidine but left the response to icv moxonidine intact. Finally, chemical sympathectomy with reserpine did not alter the response to intrarenal moxonidine suggesting that this effect was independent of the sympathetic nervous system. In conclusion, these studies indicate the ability of central and peripheral moxonidine to increase urine flow rate through sodium excretion at two unique sites of action, one central and the other one peripheral, most conceivably within the kidney.

Intravenous NBQX inhibits spontaneously occurring sympathetic nerve activity and reduced blood pressure in cats

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo( F)quinoxaline (NBQX) has been demonstrated to be a specific and competitive non-N- methyl- D-aspartate (non-NMDA) glutamate receptor antagonist. Our previous data obtained with the NMDA receptor antagonist MK-801 indicate that blockade of the NMDA receptor affects blood pressure. The purpose of this study was to determine whether the same is true with blockade of the non-NMDA receptor. For this purpose we administered three doses of NBQX (1, 3 and 10 mg/kg i.v.) to anesthetized, artificially ventilated and paralyzed cats while monitoring spontaneously occurring cardiac sympathetic nerve activity, arterial blood pressure and heart rate. The 1 mg/kg dose of NBQX i.v. reduced both sympathetic nerve activity (−29 ± 7%, P < 0.05, n = 4) and blood pressure (−27 ± 5 mm Hg, P < 0.05). Injection of 3 mg/kg NBQX produced a greater decrease in sympathetic nerve activity (−78 ± 11%, P < 0.01, n = 8) and mean arterial pressure (−47 ± 5 mm Hg) and also reduced heart rate (−11 ± 2 beats/min, P < 0.01). The depressant effects of NBQX on sympathetic nerve activity, blood pressure and heart rate were similar regardless of whether activity was recorded from pre- or postganglionic cardiac nerves, or from animals subjected to baroreceptor denervation. Intravenous injection of a total dose of 10 mg/kg NBQX completely inhibited sympathetic nerve activity (−100 ± 0%, P < 0.05, n = 3) and this effect was associated with reductions in mean arterial pressure (−49 ± 10 mm Hg, P < 0.05) and heart rate (−30 ± 6 beats/min, P < 0.05). The data indicate that NBQX i.v. decreases sympathetic nerve activity, blood pressure and heart rate in a dose-dependent manner and that the primary site of these effects is likely in the central nervous system.

Long-term sympathetic and hemodynamic responses to clonidine in patients with cirrhosis and ascites

The aim of the present study was to examine the short- and long-term effects of the alpha 2-agonist clonidine on sympathetic overactivity, systemic, splanchnic, and renal circulation changes, and abnormal renal sodium excretion in cirrhotic patients with ascites. Of 17 patients, 8 received clonidine and 9 a placebo. Measurements were taken before and after either a single dose of clonidine (150 micrograms) and placebo or a 1-week treatment with clonidine (150 micrograms/day) and placebo. Clonidine but not placebo induced significant short- and long-term decreases in plasma norepinephrine concentrations in the pulmonary artery and the right renal vein. Acute clonidine administration induced a significant reduction in cardiac output, heart rate, arterial pressure, and hepatic venous pressure gradient but had no effect on renal hemodynamics. Long-term clonidine administration induced a significant decrease in the hepatic venous pressure gradient from 20.1 +/- 1.9 to 17.6 +/- 2.0 mm Hg (mean +/- SEM) but had no significant effects on systemic or renal hemodynamics or renal excretion of sodium. It is concluded that long-term clonidine administration in cirrhotic patients induced a sustained decrease in sympathetic nervous activity and portal pressure. In contrast, clonidine had no prolonged effect on systemic hemodynamics. In addition, short- and long-term clonidine administration did not modify renal hemodynamics or induce a natriuretic response in patients with ascites. (Gastroenterology 1992 Apr;102(4 Pt 1):1309-18)

Long-term sympathetic and hemodynamic responses to clonidine in patients with cirrhosis and ascites

The aim of the present study was to examine the short- and long-term effects of the α2-agonist clonidine on sympathetic overactivity, systemic, splanchnic, and renal circulation changes, and abnormal renal sodium excretion in cirrhotic patients with ascites. Of 17 patients, 8 received clonidine and 9 a placebo. Measurements were taken before and after either a single dose of clonidine (150 μg) and placebo or a 1-week treatment with clonidine (150 μg/day) and placebo. Clonidine but not placebo induced significant short- and long-term decreases in plasma norepinephrine concentrations in the pulmonary artery and the right renal vein. Acute clonidine administration induced a significant reduction in cardiac output, heart rate, arterial pressure, and hepatic venous pressure gradient but had no effect on renal hemodynamics. Long-term clonidine administration induced a significant decrease in the hepatic venous pressure gradient from 20.1 ±1.9 to 17.6 ± 2.0 mm Hg (mean ± SEM) but had no significant effects on systemic or renal hemodynamics or renal excretion of sodium. It is concluded that long-term clonidine administration in cirrhotic patients induced a sustained decrease in sympathetic nervous activity and portal pressure. In contrast, clonidine had no prolonged effect on systemic hemodynamics. In addition, short- and longterm clonidine administration did not modify renal hemodynamics or induce a natriuretic response in patients with ascites.

Sympathoinhibition and its reversal by naloxone during hemorrhage.

During hemorrhagic hypotension, vascular resistance, plasma norepinephrine, and sympathetic nerve activity decrease. Naloxone reverses these effects. We hypothesized that increased sympathetic nerve activity was specific to naloxone and not secondary to the pressor response. Conscious rabbits were hemorrhaged until mean arterial pressure (MAP) was less than 40 mmHg, given naloxone (3 mg/kg) or saline, and monitored for 5 min. In some animals, we attenuated naloxone's pressor response with alpha-adrenergic blockade or mimicked the pressor response by infusion of phenylephrine. During nonhypotensive hemorrhage, heart rate and renal sympathetic nerve activity (RSNA) increased significantly. During hypotensive hemorrhage, RSNA decreased to significantly less than prehemorrhage control values. After saline treatment, RSNA did not increase. Naloxone significantly increased MAP and RSNA. alpha-Blockade reduced the pressor response to naloxone but not the increase in RSNA. Phenylephrine increased MAP to a level similar to naloxone, but RSNA remained suppressed. Reinfusion of hemorrhaged blood reduced RSNA in all groups treated with naloxone. These data suggest that hypotensive hemorrhage is associated with sympathoinhibition that is not transient. In addition, the pressor response to naloxone is not required for its sympathoexcitatory effects.

Interaction between the renin-angiotensin-aldosterone and sympathetic nervous systems.

The renin-angiotensin-aldosterone system is mainly involved in the regulation of arterial blood pressure and fluid balance. One of the main stimuli for the secretion of renin present in the renal juxtamedullary cells, but also in some other tissues, is provided by the sympathetic nervous system via the action of norepinephrine on beta 1-adrenoceptors. There is good evidence in animal experiments that angiotensin II (Ang II) facilitates sympathetic neurotransmission by several mechanisms, all of which seem to involve distinct, but perhaps heterogeneous, Ang II receptors. Acting within the central nervous system, angiotensin augments sympathetic nerve outflow directly, but probably also by inhibiting the reflex decrease in sympathetic nerve activity following an increase in arterial pressure. Ang II also stimulates adrenomedullary and ganglionic transmission as well as enhances the release of sympathetic transmitter by a presynaptic action. In addition, there is some evidence that angiotensin can inhibit norepinephrine reuptake and augment its biosynthesis and responses mediated via both extrasynaptic alpha 2- and intrasynaptic alpha 1-adrenoceptors. Angiotensin-converting enzyme inhibitors, particularly when the endogenous renin-angiotensin activity is high, attenuate sympathetic neurotransmission. Despite a clear demonstration that the renin-angiotensin system augments the activity of the sympathetic nervous system in animals, evidence for such a role in humans is tenuous. This is probably mainly due to the difficulty in quantitatively monitoring and assessing the autonomic function in humans. It is possible that in congestive heart failure, where the renin-angiotensin system can be highly activated, sympathetic facilitation by angiotensin as well as its attenuation by converting enzyme inhibitors may be important.

Renal sympathetic nerve and hemodynamic responses to captopril in conscious dogs: role of prostaglandins

The angiotensin converting enzyme inhibitor captopril has been shown to cause resetting of the arterial baroreflex to a lower pressure without a change in gain. The present study was conducted to determine whether captopril altered the relationship between arterial pressure, heart rate, and renal sympathetic nerve activity in conscious quietly resting dogs. Fourteen instrumented dogs were given 2 mg/kg iv of captopril; 10 min later postcaptopril measurements were made. Six of the fourteen dogs were pretreated with cyclooxygenase inhibitor (indomethacin or meclofenamate) before administration of captopril. Renal nerve activity and hemodynamics were measured in a final group of eight dogs in which arterial pressure was lowered with a graded infusion of sodium nitroprusside. Captopril caused a small but significant decrease in arterial pressure. This decrease in arterial pressure was accompanied by a significant increase in heart rate; however, renal sympathetic nerve activity was significantly reduced. In contrast, dogs receiving nitroprusside exhibited an increase in both heart rate and renal sympathetic nerve activity in response to similar decreases in arterial pressure. Dogs that received cyclooxygenase inhibitor showed reduced arterial pressure in response to captopril, increased heart rate, and increased renal sympathetic nerve activity. This study is the first to report a decrease in sympathetic nerve activity in response to captopril in an awake chronically instrumented animals. These data suggest that captopril's ability to augment prostaglandin synthesis is responsible for the observed sympathoinhibition.

Catecholamines, circulation, and the kidney during water immersion in humans

Because results in literature are discrepant with regard to the effects of water immersion (WI) on the release of norepinephrine (NE) in humans, the following study was performed. Simultaneous measurements of plasma NE, central cardiovascular variables, and renal sodium excretion were conducted in eight normal male subjects on 2 study days; 6 h of thermoneutral (35.0 degrees C) WI to the neck were preceded and followed by 1 h in the seated posture outside the water and 8 h of a seated control period. During the control period, the subjects wore a water-perfused garment (water temperature 34.6 degrees C) to obtain the same skin temperature as during WI. The subjects were fluid restricted overnight and kept in this condition throughout the study. Compared with the prestudy, post-study, and control periods, plasma NE decreased significantly by 61% during WI. Simultaneously, central venous pressure, cardiac output, stroke volume, systolic arterial pressure, and arterial pulse pressure increased, whereas heart rate decreased. Renal sodium excretion and urine flow rate increased. In conclusion, the release of NE is suppressed in humans during immersion. This decrease probably reflects a decrease in sympathetic nervous activity initiated by stimulation of low- and high-pressure baroreceptors. It is possible that the decrease in NE acts as one of several mechanisms of the natriuresis and diuresis of immersion in humans.

Sympathetic and hemodynamic adjustments to hemorrhage: A possible role for endogenous opioid peptides

The traditional view of the decrease in blood pressure during blood loss is that it is a passive phenomenon. Blood pressure falls due to the inability of the compensatory mechanisms to keep pace with blood loss. However, recent evidence indicates that this transition from normotension to hypotension may involve an active decrease in compensation by the sympathetic nervous system. In the conscious, chronically prepared rabbit, blood pressure is maintained early in hemorrhage primarily by sympathetically mediated compensatory increases in vascular resistance and heart rate. When blood loss exceeds approximately 20% of total blood volume, hypotension develops abruptly due to a decrease in vascular resistance. This vasodilation is accompanied by decreased plasma norepinephrine (NE) levels and decreased sympathetic nerve activity. Therefore, the transition from normotension to hypotension during hemorrhage involves an active change, a decrease in vascular resistance, associated with a decrease in sympathetic nerve activity. Opioid receptor blockade with naloxone reverses acute hemorrhagic hypotension by increasing vascular resistance. The increase in resistance is accompanied by increased plasma NE and increased sympathetic nerve activity. Thus, the transition to hypotension during acute hemorrhage may be an active event brought on by a decrease in sympathetic outflow. Naloxone's reversal of the hypotension is consistent with the central involvement of endogenous opioid peptides in this phenomenon and thus in the pathogenesis of hypotension during blood loss.

Postexercise hypotension and sympathoinhibition in borderline hypertensive men.

To determine if there would be a decrease in blood pressure after exercise in patients with borderline hypertension and if this decrease would be accompanied by a decrease in sympathetic nerve activity to muscle, we recorded multifiber postganglionic muscle sympathetic activity from the peroneal nerve at rest in nine men with borderline hypertension (age 25 +/- 1 years, mean +/- SEM) before and 60 minutes after 45 minutes of submaximal treadmill exercise. In addition, responses to a cold pressor test, handgrip, and the Valsalva maneuver were recorded before and after exercise. Four subjects were also studied before and after "sham" exercise. Sham exercise had no effect on blood pressure or sympathetic nerve activity whereas resting systolic blood pressure was lower after treadmill exercise in seven subjects (from 136 +/- 4 before to 123 +/- 2 mm Hg 60 minutes after exercise; p less than 0.01). Sixty minutes after exercise, sympathetic nerve activity was lower in all seven subjects (from 19 +/- 2 to 11 +/- 2 bursts/min, p less than 0.015; or from 27 +/- 3 to 14 +/- 2 bursts/100 heartbeats, p less than 0.005) but was slightly increased in the two subjects without postexercise hypotension. Heart rate and pressor and sympathoneural responses to the cold pressor test, handgrip, and the Valsalva maneuver were not altered by prior exercise. When nitroprusside was infused in five subjects to produce a reduction in systolic blood pressure similar to that seen 60 minutes after exercise, this drug increased sympathetic discharge from 37 +/- 6 to 57 +/- 4 bursts/100 heartbeats (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Sympatholytic effects of the intravenously injected alpha 1-adrenergic blocker, bunazosin, in anaesthetized rats.

Cardiovascular regulation during alpha 1-adrenergic blocker-induced vasodepression was investigated in urethane-anaesthetized rats. Intravenous (i.v.) injections of bunazosin, an alpha 1-blocker, elicited depressor responses which were accompanied by corresponding decreases in both heart rate and abdominal sympathetic discharge, dose-dependently. Those responses were not affected by the bilateral sino-aortic de-afferentation. Assuming that the site of action is in the central nervous system, bunazosin was injected intracerebroventricularly (i.c.v.). It produced hypotension accompanied by decreases in heart rate and abdominal sympathetic nerve activity. The magnitude of the responses was greater when bunazosin was injected i.c.v. than when injected i.v. Since these results indicated that the central alpha 1-adrenergic receptors mediate vasopressor responses, the effects of i.c.v. injections of an alpha 1-agonist, phenylephrine was explored. It elicited vasopressor responses accompanied by corresponding increases in heart rate and abdominal sympathetic nerve activity. Furthermore, i.c.v. pretreatment with bunazosin abolished the vasopressor responses to i.c.v. injections of phenylephrine. These results indicate that central alpha 1-adrenergic receptors mediate vasopressor responses and that i.v. injections of alpha 1-blockers affect the central alpha 1-receptors, to produce a decrease in sympathetic nerve activity. Consequently, alpha 1-adrenergic blockers decrease blood pressure not only by peripheral vasodilation but also by inhibition of the sympathetic outflow in rats.

Inhibition of muscle sympathetic nerve activity in humans by arginine vasopressin.

Arginine vasopressin, a potent vasoconstrictor, does not raise arterial pressure in normal humans even at pathophysiological plasma levels. To examine whether the pressor effect of vasopressin in humans is buffered by baroreceptor reflex inhibition of sympathetic nerve activity, we recorded postganglionic muscle sympathetic nerve activity directly from the peroneal nerve in 12 normal men before, during, and after a 20-minute intravenous infusion of vasopressin, 4 ng/kg/min, that increased mean plasma concentrations from 6.2 +/- 0.6 to 320 +/- 68 (SE) pg/ml. During the first 5 minutes (n = 8), mean arterial pressure increased from 91 +/- 3 to 97 +/- 4 mm Hg (p less than 0.05) and integrated sympathetic nerve activity decreased from 271 +/- 45 to 156 +/- 33 units (p less than 0.05). At 15 minutes (n = 12), arterial pressure did not differ from control values whereas forearm vascular resistance fell (p less than 0.05) and central venous pressure and heart rate increased (p less than 0.05). Sympathetic nerve activity remained below control levels throughout the infusion (202 +/- 31 vs 254 +/- 40 units before infusion; p less than 0.05). An effect of vasopressin on ganglionic transmission was excluded, since the sympathoexcitatory response to apnea was not attenuated during vasopressin. Thus, pathophysiologic levels of vasopressin in humans cause inhibition of muscle sympathetic nerve activity that is not due to a ganglionic blocking action. The sympathoinhibition may be caused in part by the modest increases in mean arterial and central venous pressures and attendant stimulation of arterial and cardiac baroreceptors. The reflex decrease in sympathetic nerve activity would be expected to buffer the direct vasoconstrictor effects of vasopressin.

Brain Glutathione and Blood Pressure Control

The role of glutathione in the central nervous system in regulating blood pressure (BP) and sympathetic nerve activity (SNA) was investigated in rats. Intracerebroventricular (ICV) injection of glutathione disulfide (GSSG: 1.7-33 nmol) resulted in a dose-dependent increase in BP [Δ mean BP: 17 ± 1 mm Hg (n = 7) for 33-nmol dose] together with a marked increase in SNA [163 ± 13 to 672 ± 70 spikes/10 s (n = 7), p < 0.001]. Intracerebroventricular administration of its reduced form (GSH, 33 nmol) produced a vasodepressor response (Δ mean BP: -9 ± 2 mm Hg) accompanied by a corresponding decrease in SNA [192 ± 15 to 54 ± 22 spikes/ 10 s (n = 6), p < 0.01]. These responses were not due to a leakage into the systemic circulation, since intravenous injection of GSSG or GSH (33 nmol) did not show any cardiovascular effects. Electrical stimulation of the posterior hypothalamus induced hypertension with a significant decrease of GSSG in the brain stem. The results indicate that GSSG has a stimulatory control over the sympathetic nervous system while GSH has an inhibitory effect on SNA. Glutathione disulfide and GSH may act within the central nervous system to modulate the tone of the sympathetic nervous system.

Chronic sodium depletion suppresses the area postrema pressor pathway

Sodium depletion in dogs is known to affect both the renin-angiotensin as well as the sympathetic nervous system. The effect of this dietary regime upon the area postrema pressor pathway, as evaluated by the cardiovascular responses to centrally acting angiotensin II, has not been determined previously. With this in mind, male mongrel dogs were maintained on Either a normal or a sodium restricted diet supplemented with furosemide and dose-response curves for intravertebral and intravenous angiotensin II (range: 1–20 ng/kg/min) were obtained. Sodium depletion results in not only a blunted intravenous pressor response to angiotensin II but also the abolition of the centrally mediated pressor responses mediated by the area postrema. Because accumulating evidence indicates that in sodium depleted dogs sympathetic nerve activity is reduced while central noradrenergic inhibitory activity is increased the reduced effects of angiotensin II upon the central sympathetically mediated pressor response may in part be related to decreases in sympathetic nerve activity.

Brain Glutathione and Blood Pressure Control

The role of glutathione in the central nervous system in regulating blood pressure (BP) and sympathetic nerve activity (SNA) was investigated in rats. Intracerebroventricular (ICV) injection of glutathione disulfide (GSSG: 1.7-33 nmol) resulted in a dose-dependent increase in BP [delta mean BP: 17 +/- 1 mm Hg (n = 7) for 33-nmol dose] together with a marked increase in SNA [163 +/- 13 to 672 +/- 70 spikes/10 s (n = 7), p less than 0.001]. Intracerebroventricular administration of its reduced form (GSH, 33 nmol) produced a vasodepressor response (delta mean BP: -9 +/- 2 mm Hg) accompanied by a corresponding decrease in SNA [192 +/- 15 to 54 +/- 22 spikes/10 s (n = 6), p less than 0.01]. These responses were not due to a leakage into the systemic circulation, since intravenous injection of GSSG or GSH (33 nmol) did not show any cardiovascular effects. Electrical stimulation of the posterior hypothalamus induced hypertension with a significant decrease of GSSG in the brain stem. The results indicate that GSSG has a stimulatory control over the sympathetic nervous system while GSH has an inhibitory effect on SNA. Glutathione disulfide and GSH may act within the central nervous system to modulate the tone of the sympathetic nervous system.

High salt diet sensitizes cardiopulmonary baroreflexes in Dahl salt-resistant rats.

Compared with Dahl salt-resistant (R) rats, Dahl salt-sensitive (S) rats on a low salt diet have impaired cardiopulmonary baroreflex control of sympathetic nerve activity. The purpose of this study was to examine the sensitivity of cardiopulmonary baroreflex function in both strains of Dahl rats when they are challenged with a high salt diet. We studied Dahl R and S rats after 6 weeks of low and high salt diets. To assess cardiopulmonary baroreflex function, we measured decreases in splanchnic sympathetic nerve activity produced by increases in left ventricular end-diastolic pressure during graded volume expansion (dextran 75) after bilateral sinoaortic denervation. A given amount of infused volume produced comparable increases in left ventricular end-diastolic pressure in Dahl R rats on low and high salt diets but significantly greater decreases in sympathetic nerve activity in the high salt group than in the low salt group. Thus, the high salt diet augmented the sympathoinhibitory response to volume expansion in the Dahl R rats. In contrast, among the Dahl S rats equivalent increases in left ventricular end-diastolic pressure during volume expansion produced smaller sympathoinhibitory responses in the high salt group than in the low salt group. The gain of the cardiopulmonary baroreflex, expressed as the percentage decrease in sympathetic nerve activity per mm Hg increase in left ventricular end-diastolic pressure, was significantly increased by a high salt diet in Dahl R rats but tended to be decreased by a high salt diet in Dahl S rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Actions of Neuronal and Hormonal Vasopressin on Blood Pressure and Baroreceptor Reflex Sensitivity in Rats

The central cardiovascular actions of arginine vasopressin (AVP) and the role of this peptide in the modulation of baroreceptor reflex (BRR) sensitivity were investigated in conscious, chronically instrumented rats. Intracerebroventricular (i.c.v.) injections of AVP (1-100 ng) produced dose-dependent pressor effects together with increases in heart rate, splanchnic, and renal sympathetic nerve activity and a reduction of mesenteric blood flow. These responses were prevented by i.c.v. pretreatment with a V1-AVP receptor antagonist. Furthermore, the central pressor effects of AVP were abolished by peripheral alpha-adrenoceptor blockade with phentolamine. In contrast to the i.c.v. injections, intravenous (i.v.) or intracarotid injections of AVP produced pressor responses accompanied by bradycardia and a decrease in sympathetic nerve activity. Intracerebroventricular pretreatment with a V1-AVP receptor antagonist shifted the slope of the BRR curve (increases in pulse interval plotted against increases in systolic blood pressure in response to i.v. methoxamine) toward higher sensitivity, whereas i.v. pretreatment with a V2-AVP receptor antagonist shifted the slope of the BRR curve toward lower sensitivity of the reflex. These findings suggest that central (neuronal) AVP, by acting on V1-AVP receptors in the brain, participates in central pressor mechanisms, activates the sympathetic nervous system, and desensitizes the BRR. Conversely, circulating (hormonal) AVP can sensitize the BRR by acting on V2-AVP receptors accessible from the blood. Our data provide evidence pointing to a direct interaction between the neuronal and the hormonal axis of the AVP system within cardiovascular control.