Cholinergic stimulation of vasopressin release in spontaneously hypertensive rats.

Plasma vasopressin (VP) concentration is elevated in spontaneously hypertensive rats (SHRs) relative to their normotensive Wistar-Kyoto (WKY) controls. The possibility that this reflects altered responsiveness of the hypothalamo-neurohypophyseal system (HNS) in SHRs was examined by comparing VP release in response to acetylcholine from organ cultured HNS explants obtained from SHR and WKY donors. Explants were prepared from 5-, 8-, and 18-week-old animals. Blood pressure was significantly elevated in the 8- and 18-week-old SHR donors relative to their age-matched WKY donors. VP release was assessed on the 4th day of culture during a control hour and during the subsequent hour in the presence of acetylcholine. Acetylcholine caused a concentration-dependent stimulation of VP release from both types of explants, but the response was significantly greater in the explants from 5- and 8-week-old SHRs than in explants from age-matched WKYs. The explants from 18-week-old SHRs and WKYs demonstrated comparable sensitivity to acetylcholine. Basal VP release was not significantly different in explants from age-matched SHRs and WKYs, but it did increase with donor age in both strains. These studies indicate potential hyperresponsiveness of the HNS to excitatory stimuli in SHRs during the developmental phase of hypertension. The hyperresponsiveness disappears in the chronically hypertensive phase. Thus, increased sensitivity of the HNS during the development of hypertension may contribute to the elevation of plasma VP concentration in SHRs.

Evidence against a pressor role for vasopressin in spontaneous hypertension.

The hypothesis that the vasoconstrictor action of vasopressin may contribute to the development of hypertension in spontaneously hypertensive rats (SHR) was tested by chronic infusion of a specific antagonist of the vascular effects of vasopressin. From 4 to 13 weeks of age, SHR and Wistar-Kyoto rats (WKY) received subcutaneously either isotonic saline or the vasopressin pressor antagonist, d(CH2)5Tyr(Me)arginine vasopressin by osmopump. Systolic blood pressure was measured by tail cuff from 5 to 11 weeks of age. In SHR, the vasopressin analogue did not alter the rate or magnitude of increase in systolic blood pressure. In WKY, systolic blood pressure in the vasopressin analogue group was slightly reduced compared with the saline infusion values until 10 weeks of age (F1, 10 = 10.18, p = 0.008). At 12 to 14 weeks of age, all animals were prepared with indwelling arterial and venous catheters. Resting mean arterial pressure was not altered significantly by the vasopressin analogue infusion in either strain, but the response to an acute vasopressin infusion of 5, 15, or 50 ng/kg body weight was markedly attenuated by the analogue treatment, indicating that plasma levels of the vasopressin analogue were sufficient to block pressor effects of endogenous vasopressin. A bolus injection of the angiotensin II converting enzyme inhibitor teprotide (SQ 20881) resulted in a decrease in mean arterial pressure (p less than 0.05) that was comparable in all groups, and serum renin concentration was not elevated in the vasopressin analogue-treated rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation of spontaneous hypertension in rats by a vasopressin antagonist.

Although abnormalities in the vasopressin system have been reported in spontaneously hypertensive rats (SHR), neither short-term nor long-term administration of the vasopressin antagonist d(CH2)5-Tyr(Me)arginine vasopressin (AVP), which selectively blocks the action of vasopressin on vascular (V1) receptors, altered the course of hypertension in SHR. In the current study, long-term administration of a different vasopressin antagonist, d(CH2)5-D-Tyr(Me)VAVP, to SHR and Wistar-Kyoto rats (WKY) from 4 to 12 weeks of age significantly attenuated the development of systolic hypertension in SHR (p less than 0.05) without altering blood pressure in normotensive WKY. The antagonist was delivered subcutaneously by osmopump at 0.1 microgram/hr. Systolic blood pressure was monitored twice weekly by tail plethysmography beginning at 5 weeks of age. In a second group of SHR, the drug infusion was continued until 18 weeks of age. In this group, the attenuation of systolic hypertension by the drug was extended and became more prominent (p less than 0.007). Resting mean arterial pressure measured by indwelling catheters in the conscious state at 18 weeks of age was significantly reduced in the antagonist-treated SHR (144 +/- 4 vs 157 +/- 4 mm Hg; p less than 0.05). Heart rate also was significantly reduced by the drug (351 +/- 6 vs 392 +/- 7 beats/min; p less than 0.001). Following measurement of mean arterial pressure in the rats at 18 weeks of age, the osmopumps were removed and systolic blood pressure, mean arterial pressure, and heart rate were observed until 22 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

The area postrema in deoxycorticosterone-salt hypertension in rats.

Ablation of the area postrema in rats prevents sustained hypertension during angiotensin II infusion and after unilateral renal artery constriction (two-kidney, one clip hypertension). The current experiment was performed to determine whether an intact area postrema is required for hypertension development in a low renin model of experimental hypertension in rats. In 11 rats, the area postrema was destroyed using electrical current; the extent and specificity of each lesion was confirmed later by blind histological analysis. In 12 rats, sham operations were performed. All rats were uninephrectomized and drank saline. During once-weekly injections of deoxycorticosterone pivalate (5 mg/wk) for 4 weeks, sham-operated rats (n = 10) showed a significant increase in mean arterial pressure (Days 6-28) and saline intake (Days 12-28), but no significant increase in sodium or water retention. Deoxycorticosterone-treated rats with area postrema ablation (n = 9) exhibited no change in arterial pressure, sodium retention, or water retention, but a significant increase in saline intake (Days 17-28). Plasma renin activity was equally suppressed in both groups of rats. The depressor response to ganglion blockade with hexamethonium (20 mg/kg i.v.) was significantly increased during the 2nd, 3rd, and 4th weeks of steroid treatment in sham-operated, but not area postrema-ablated, rats. Four rats (2 sham-operated; 2 ablated) showed no change in any variable over 28 days in the absence of steroid treatment. It is concluded that the area postrema may be important in some non-angiotensin-dependent forms of experimental hypertension, possibly by affecting neurogenic control mechanisms.

Osmotic regulation of vasopressin and renin in spontaneously hypertensive rats.

Abnormalities in the vasopressin and renin systems have been reported in spontaneously hypertensive rats (SHR). Therefore, studies were performed to evaluate the responsiveness of these systems to changes in plasma osmolality and sodium concentration. These variables were manipulated in vivo by intraperitoneal administration of distilled water, isotonic saline, or hypertonic saline to 8- and 18-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Animals were decapitated 30 minutes later, and trunk blood was collected. The hypertonic saline injections resulted in an increase in plasma osmolality and serum sodium at both ages (p less than 0.001). Serum vasopressin was higher in all groups of animals receiving hypertonic saline (1200 mosm/kg H2O; p less than 0.05), but the magnitude of increase was not significantly different in the SHR and WKY at either age. Serum renin activity was lower in SHR than in WKY following acute decreases in serum sodium at 8 weeks, but it was the same for both strains at 18 weeks. Both kidney renin content and concentration were lower in SHR than in WKY at 18 weeks but not at 8 weeks. Therefore, the suppressed renin response to acute osmotic challenge in 8-week-old SHR is not the consequence of reduced kidney renin content. The vasopressin response to osmotic stimulation also was evaluated in vitro using hypothalamoneurohypophyseal explants obtained from 5-, 8-, and 18-week-old SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressin and renin response to dehydration in aged rats.

Abnormalities in neurohypophyseal function have been postulated to contribute to the alterations in fluid and electrolyte balance observed during aging. In this study, parameters of fluid and electrolyte balance were evaluated during chronic water deprivation in old (30 months) and young (3 months) Fischer 344 rats. The increase in serum vasopressin (VP) and renin concentrations observed in the 3 month animals following chronic water deprivation were absent in the aged rats (p less than 0.05 and p less than 0.02, respectively). This occurred in spite of apparently comparable alterations in fluid volume and osmolality (assessed by changes in body weight, hematocrit and plasma osmolality). Relative to body weight, VP content of the neural lobe was significantly reduced and was more severely depleted by dehydration in aged rats than in young rats. Thus, inadequate neurohypophyseal hormone stores may contribute to the inability of the aged animals to attain elevated serum VP concentrations during chronic stimulation. Several parameters of renal function were examined in the aged rats. Although none of the old rats were in renal failure, they all showed some indication of reduced renal function. In spite of renal abnormalities including reduced concentrating capabilities, the old rats did demonstrate a significant antidiuretic response to dehydration. However, with prolonged fluid deprivation, they were unable to attain serum VP or renin concentrations comparable to that achieved by the young rats.

Abnormalities in hypothalamic and neurohypophysial vasopressin content are not a consequence of hypertension in the spontaneously hypertensive rat.

In order to determine if the decreased hypothalamic and increased posterior pituitary content of vasopressin (VP) observed previously in spontaneously hypertensive rats (SHR) were a secondary consequence of the hypertension, the effect of preventing the development of hypertension on VP content of the hypothalamoneurohypophyseal system was evaluated. Two methods for preventing the hypertension were used: (1) chronic angiotensin-converting enzyme inhibition (oral captopril, 100 mg/kg/day at 4-12 weeks of age); and (2) intraventricular 6-hydroxydopamine (6-OHDA, 200 micrograms at 4 and 5 weeks of age). Both of these treatments markedly attenuated the increase in systolic blood pressure in SHRs at 5-11 weeks of age. The captopril-treated rats had a significant elevation in serum renin activity at 12 weeks of age indicating the presence of chronic converting enzyme inhibition, and the 6-OHDA-treatment resulted in a depletion of hypothalamic (86%) and brainstem (76%) norepinephrine content. Hypothalamic VP content was reduced in untreated SHRs compared to normotensive Wistar-Kyoto rats (WKYs, P = 0.0015). It was not significantly altered in either strain by the 6-OHDA treatment. Captopril caused a reduction in hypothalamic VP content in both SHRs and WKYs (P less than 0.01). Posterior pituitary VP content was elevated in untreated SHRs compared to WKYs (P less than 0.001), and remained elevated with captopril and 6-OHDA treatments. These data indicate that the abnormalities in VP content in the hypothalamus and posterior pituitary of SHRs are not a response to the hypertension. Therefore, they may represent primary abnormalities in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lesions of hypothalamic catecholamines on blood pressure, fluid balance, vasopressin and renin in the rat.

Fluid balance, systolic blood pressure (BP) and serum vasopressin (VP) and renin activity (SRA) in the basal state and in response to blood volume depletion were examined in unanesthetized rats previously given intrathecal 6-hydroxydopamine (6-OHDA) to destroy catecholaminergic (CA) input to supraoptic nucleus (SON). Sham-operated rats, unoperated ad libitum hydrated rats and rats undergoing 4 days of water deprivation served as controls. The 6-OHDA lesion resulted in adipsia, a failure to conserve administered fluids and a decrease in systolic BP. Despite decreased blood volume secondary to dehydration, and decreased systolic BP, the 6-OHDA group failed to show the expected increase in serum VP. However, when blood volume was further decreased following intraperitoneal polyethylene glycol, lesioned rats showed robust VP and SRA responses. Thus, CA input to critical target areas in the hypothalamus may be necessary for maintenance of sensitivity to stimuli that normally elicit VP release. Decreased systolic BP following 6-OHDA lesions most likely results from dehydration coupled with inadequate VP responses.

Conditioned increase in peripheral blood mononuclear cell (PBMC) number and corticosterone secretion in the rat.

Femoral artery catheters were surgically implanted into male Lewis/N rats to allow blood sampling and drug infusion in the freely moving animal. After recovery, conditioned animals received four pairings of a peppermint odor, the conditioned stimulus (CS), and an infusion of 0.1 mg/kg nicotine bitartrate, an unconditioned stimulus (US) for an increase in the number of peripheral blood mononuclear cells (PBMC) and an increase in corticosterone concentration. When reexposed to the peppermint odor, conditioned animals showed a significant increase in PBMC number and corticosterone secretion when compared to saline and unpaired control groups and previously conditioned animals that were not reexposed to the CS. Increased PBMCs were found on the fifth unreinforced CS trial. Conditioned CORT responses were lost after the initial test trial. The data indicate that the distribution of immune cells can be influenced by learning processes and support the role of learning in the regulation of corticosterone secretion.

Inhibition of renin secretion by intrarenal alpha-adrenoceptor blockade.

This study was designed to determine whether renal alpha-adrenoceptors can mediate tonic neural stimulation of renin secretion. The effect of alpha-adrenoceptor blockade by phenoxybenzamine (POB) or prazosin on renin secretion rate (RSR) was studied in pentobarbital-anesthetized dogs in which renal perfusion pressure was held constant with an adjustable aortic clamp. POB alone (100 micrograms.kg-1.min-1 iv) did not change arterial plasma renin activity (PRA). However, when beta-adrenoceptors were blocked by intravenous propranolol, intravenous POB infusion (100 micrograms.kg-1.min-1) decreased PRA and RSR to 48 +/- 8 and 21 +/- 9% of previous levels within 30 min. This effect was abolished by acute bilateral renal denervation. Direct intrarenal POB infusion (10 or 3.3 micrograms.kg-1.min-1) decreased RSR, whereas intravenous POB (3.3 micrograms.kg-1.min-1) had no effect on either RSR or PRA in propranolol-pretreated dogs. Prazosin (1 microgram.kg-1.min-1 iv) also significantly decreased PRA. These data indicate that when beta-adrenoceptors are blocked by propranolol, tonic neural stimulation of renin secretion is mediated by renal alpha-adrenoceptors.

Stimulation of renin secretion by alpha-adrenoceptor agonists.

This study was designed to determine whether stimulation of intrarenal alpha-adrenoceptors can increase renin secretion rate (RSR) in the absence of increased renal vascular resistance and to identify the accompanying changes in renal function. Experiments were performed in pentobarbital-anesthetized dogs in which renal perfusion pressure was maintained at approximately 90 mmHg and the infused kidney was acutely denervated. Renal artery infusion of the alpha-adrenoceptor agonist methoxamine (0.5 microgram X kg-1 X min-1 for 30 min) increased RSR from 160 +/- 95 to 1,376 +/- 385 ng ANG I/min (P = 0.01) but did not decrease renal blood flow (RBF); the same dose infused intravenously had no effect on RSR or RBF. Intra-arterial phenylephrine infusion (0.5 microgram X kg-1 X min-1 for 9 min) increased RSR by 500 +/- 157 ng ANG I/min (P less than 0.01) and decreased both inulin clearance (Cin) and urinary sodium excretion (UNaV) by 25% but did not affect RBF. At a lower concentration of phenylephrine (0.2 microgram X kg-1 X min-1 for 9 min), RSR increased by 318 +/- 103 ng ANG I/min (P less than 0.01) and RBF, Cin, and UNaV did not change. The increase in RSR was completely blocked by prazosin but was unaffected by propranolol. In summary, renin secretion can be stimulated by activation of intrarenal alpha-adrenoceptors even in the absence of increased renal vascular resistance.

Female reproductive cycle influences plasma volume and protein restitution after hemorrhage in the conscious rat.

The present study was designed to test the hypothesis that gender and female reproductive cycle phase influence the restitution of blood volume following blood loss. The experiments were performed in conscious 9- to 11-wk-old Sprague-Dawley rats subjected to a slow hemorrhage of 19 ml/kg over 40 min. The effect of hemorrhage was compared in male rats and in female rats in either proestrus (Pro) or metestrus (Met). In comparison with either metestrus females or males, females hemorrhaged on the morning of proestrus showed a significantly larger overall decrease in percent hematocrit (Pro, -17 +/- 1; Met, -10 +/- 1; male, -13 +/- 1; mean +/- SE), increase in plasma volume (Pro, to 151 +/- 15% of initial volume; Met, 104 +/- 8%; male, 120 +/- 4%), and increase in total plasma protein content (Pro, to 164 +/- 14% of initial content; Met, 101 +/- 5%; male, 132 +/- 5%) over the 21-h posthemorrhage recovery period. Proestrus females also showed a larger increase in plasma osmolality during the first 2.5-h posthemorrhage than either metestrus females or males (P < 0.05). In addition, basal hematocrit and total blood volume (51Cr-tagged erythrocyte method) were higher in females studied on the morning of proestrus than in metestrus females. These results indicate that the female reproductive cycle is an important variable in basal blood volume regulation and in plasma protein and plasma volume restitution following blood loss.

Beta-adrenergic control of renin in sodium-deprived conscious dogs: renal versus extrarenal location.

This study was designed to determine if tonic beta-adrenergic control of plasma renin activity (PRA) during dietary sodium restriction is due to stimulation of renal beta-adrenoceptors, extrarenal beta-adrenoceptors, or both. Experiments were performed in six conscious resting uninephrectomized dogs with chronically indwelling catheters in the aorta, vena cava, and remaining renal artery. The dogs were fed a low-sodium diet of approximately 7 mequiv. Na/day. PRA decreased by 28 +/- 4% of control (p < 0.01) when the beta-adrenoceptor antagonist propranolol was infused directly into the renal artery (ira) at a rate of 0.25 micrograms.kg-1.min-1 for 45 min, whereas iv propranolol infusion at the same rate had no effect on PRA. Propranolol infusion, 1 microgram.kg-1.min-1 iv, decreased PRA by 22 +/- 8% of control (p < 0.05) and produced significantly greater systemic beta-adrenoceptor blockade but a similar renal plasma propranolol concentration as with ira infusion, 0.25 micrograms.kg-1.min-1. Thus blockade of extrarenal beta-adrenoceptors produced no additional suppression of PRA beyond that which could be accounted for by blockade of renal beta-adrenoceptors. Therefore, suppression of PRA by propranolol is due solely to blockade of renal beta-adrenergic receptors in conscious sodium-deprived dogs.

Sympathetic activation cannot fully account for increased plasma renin levels during water deprivation.

This study was designed to determine if the increase in plasma renin activity (PRA) that occurs during water deprivation is mediated by the renal sympathetic nerves or adrenomedullary catecholamine release. Male Sprague-Dawley rats were studied while conscious and unrestrained. In intact or sham-operated rats, 48 h of water deprivation resulted in at least a threefold increase in PRA and plasma renin concentration (PRC) but no significant change in plasma norepinephrine or epinephrine concentration. Renal denervation decreased basal PRA, reduced the magnitude of the dehydration-induced PRA increase by 33%, and abolished the renin-suppressing effect of l-propranolol infusion in water-deprived rats. Adrenal demedullation also reduced basal and water-deprived PRA and PRC. However, even the combination of renal denervation and adrenal demedullation did not prevent a significant renin response to dehydration (control PRA of 1.8 +/- 0.6 ng x ml(-1) x h(-1) to dehydration PRA of 6.8 +/- 1.3 ng x ml(-1) x h(-1), P < 0.05). Therefore, some mechanism in addition to sympathoadrenomedullary activation plays a major role in mediating increased PRA during water deprivation.

Influence of renal perfusion pressure on alpha- and beta-adrenergic stimulation of renin release.

Experiments were performed in pentobarbital-anesthetized dogs to 1) determine if neural stimulation of renin release can be mediated by renal alpha-adrenoceptors at renal nerve stimulation (RNS) frequencies that have little or no effect on total renal blood flow (less than or equal to 1.2 Hz) and 2) ascertain whether alpha-adrenergic control of renin release is affected by renal perfusion pressure (RPP). The renal nerves were electrically stimulated both in the absence of RPP control and with RPP controlled near 85 mmHg. Decreased RPP lowered the threshold for neurogenic stimulation of renin release from less than or equal to 1.2 to 0.3 Hz. beta-Adrenoceptor blockade with propranolol blunted the renin secretion rate (RSR) response to graded RNS (0.3-5.0 Hz), but the extent of inhibition during low-frequency RNS was dependent on RPP. Propranolol prevented increased RSR at 0.6-1.2 Hz RNS when RPP was 111-120 mmHg but not when RPP was 85 mmHg. Combined alpha- and beta-blockade with prazosin and propranolol totally prevented increased RSR during 0.6-1.2 Hz RNS at reduced RPP. In summary, both alpha- and beta-adrenoceptors mediate neural stimulation of renin release at RNS frequencies that do not decrease total renal blood flow when RPP is 85 mmHg.

Effect of L-dopa on plasma renin activity with and without inhibition of extracerebral dopa decarboxylase in dogs.

The aim of the present study was to investigate the possibility that catecholaminergic pathways within the central nervous system play a role in the control of renin secretion. Plasma renin activity (PRA) was measured after intravenous administration of L-dopa with and without prior inhibition of extracerebral dopa decarboxylase by carbidopa (MK-486) in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were minimized by means of a suprarenal aortic clamp. When L-dopa (20 mg/kg ) was administered intravenously without carbidopa. PRA and blood pressure increased. In contrast, administration of L-dopa (20 mg/kg i.v.) after blockade of extracerebral, but not cerebral dopa decarboxylase by intravenous carbidopa (20 mg/kg), produced significant decrease in both PRA and blood pressure. Larger doses of l-dopa (30-50) mg/kg i.v.) also lowered both PRA and blood presure in three carbidopa-treated animals, whereas a smaller dose of L-dopa (10 mg/kg i.v.) significantly lowered blood pressure but not PRA. In dogs with both kidneys acutely denervated, L-dopa (20 mg/kg i.v.) with carbidopa lowered arterial pressure but did not consistently alter PRA. These data suggest that catecholamines formed within the central nervous system can act to lower renin secretion as well as blood pressure.

Elevation of plasma renin activity by alpha-adrenoceptor agonists in conscious dogs.

Experiments were performed in conscious trained dogs to determine whether renal alpha-adrenergic receptors mediate stimulation or inhibition of renin release. All dogs were uninephrectomized and surgically prepared with chronically indwelling catheters in the aorta, vena cava, and remaining renal artery at least 8 days before experiment. Direct renal artery (ia) infusion of the alpha-adrenoceptor agonist phenylephrine, 0.25 or 0.50 microgram X kg-1 X min-1 for 30 min, increased plasma renin activity (PRA) to 145 +/- 13 and 212 +/- 28% of control, respectively, within 5 min of drug infusion (P less than 0.01) in conscious sodium-replete dogs. In contrast, intravenous phenylephrine infusion decreased PRA by 50% (P less than 0.001). The increase in PRA observed during ia phenylephrine infusion was prevented by renal alpha-adrenoceptor blockade with phenoxybenzamine but not by beta-adrenoceptor blockade with propranolol. Methoxamine, another alpha-adrenoceptor agonist, also increased PRA when infused ia in both sodium-replete dogs and in dogs maintained on a low-sodium diet. In dogs with renal arterial electromagnetic flowprobes, ia phenylephrine infusion increased PRA without decreasing total renal blood flow. In summary, stimulation of renal alpha-adrenoceptors increases PRA in conscious dogs. This stimulation can occur in the absence of significant changes in total renal blood flow.

Forebrain pathways mediating stress-induced hormone secretion.

Exposure to hostile conditions initiates the secretion of several hormones, including corticosterone/cortisol, catecholamines, prolactin, oxytocin, and renin, as part of the survival mechanism. Such conditions are often referred to as "stressors" and can be divided into three categories: external conditions resulting in pain or discomfort, internal homeostatic disturbances, and learned or associative responses to the perception of impending endangerment, pain, or discomfort ("psychological stress"). The hormones released in response to stressors often are referred to as "stress hormones" and their secretion is regulated by neural circuits impinging on hypothalamic neurons that are the final output toward the pituitary gland and the kidneys. This review discusses the forebrain circuits that mediate the neuroendocrine responses to stressors and emphasizes those neuroendocrine systems that have previously received little attention as stress-sensitive hormones: renin, oxytocin, and prolactin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABAA, histamine, and serotonin receptors alter the neuroendocrine stress response. The effects of these drugs are discussed in relation to their effects on forebrain neural circuits that regulate stress hormone secretion. For psychological stressors such as conditioned fear, the neural circuits mediating neuroendocrine responses involve cortical activation of the basolateral amygdala, which in turn activates the central nucleus of the amygdala. The central amygdala then activates hypothalamic neurons directly, indirectly through the bed nucleus of the stria terminalis, and/or possibly via circuits involving brainstem serotonergic and catecholaminergic neurons. The renin response to psychological stress, in contrast to those of ACTH and prolactin, is not mediated by the bed nucleus of the stria terminalis and is not suppressed by benzodiazepine anxiolytics. Stressors that challenge cardiovascular homeostasis, such as hemorrhage, trigger a pattern of neuroendocrine responses that is similar to that observed in response to psychological stressors. These neuroendocrine responses are initiated by afferent signals from cardiovascular receptors which synapse in the medulla oblongata and are relayed either directly or indirectly to hypothalamic neurons controlling ACTH, prolactin, and oxytocin release. In contrast, forebrain pathways may not be essential for the renin response to hemorrhage. Thus current evidence indicates that although a diverse group of stressors initiate similar increases in ACTH, renin, prolactin, and oxytocin, the specific neural circuits and neurotransmitter systems involved in these responses differ for each neuroendocrine system and stressor category.

Renal norepinephrine overflow during graded renal nerve stimulation before and after beta-adrenoceptor blockade.

These experiments were designed to determine if renal venous norepinephrine (NE) overflow provides a valid index of renal sympathetic nerve activity. In addition, we evaluated the effect of beta-adrenoceptor blockade on renal NE overflow during graded renal nerve stimulation in order to examine the possibility that presynaptic beta-adrenoceptors facilitate neuronal release of NE in the kidney. In 6 pentobarbital-anesthetized dogs, the renal nerves were transected to remove tonic nerve activity and the distal ends were electrically stimulated (8-25 V, 0.5 ms) over the range of 0.3-5.0 Hz for consecutive 4-min periods. NE overflow rate was calculated as the product of the veno-arterial NE concentration difference and renal plasma flow. Control values of NE overflow (-8.7 +/- 1.8 ng/min) demonstrated net clearance of NE from the renal circulation. NE overflow rate rose to -3.1 +/- 2.2, 1.0 +/- 4.0, and 33.2 +/- 15.4 ng/min at 0.3, 0.6, and 1.2 Hz stimulation, respectively, with no accompanying change in renal blood flow. At 2.4 and 5.0 Hz, renal blood flow decreased by 21 +/- 4% and 37 +/- 3%, but there was no further increase in NE overflow rate (38.8 +/- 9.4 and 27.8 +/- 6.5 ng/min). Propranolol (0.5-1.0 mg . kg-1 plus 0.4-0.5 mg . kg-1 i.v., n = 4) did not alter the effect of nerve stimulation on either NE overflow or renal blood flow. Thus we were unable to demonstrate the presence of functional renal presynaptic beta-adrenoceptors. Further, our data indicate that renal norepinephrine overflow rate is not always a reliable index of renal nerve activity, since NE overflow was not proportional to renal nerve stimulation rate at frequencies high enough to cause vasoconstriction.