Is the sympathoexcitatory effect of yohimbine determined by brain yohimbine concentration?

Plasma noradrenaline and adrenaline concentrations, plasma renin concentration (PRC), and serum and brain yohimbine concentrations were measured in conscious Sprague-Dawley rats after the s.c. and i.v. injection of yohimbine. The s.c. and i.v. administration of 1 and 3 mg/kg of yohimbine (30 min post-injection) elicited equivalent and dose-related increases in plasma noradrenaline concentration. At 30 min post-injection, the 1 mg/kg dose given s.c. or i.v. did not increase plasma adrenaline concentration or PRC, whereas the 3 mg/kg dose caused comparable increases in plasma adrenaline concentration and PRC when given s.c. or i.v. Brain yohimbine concentration increased in a dose-related manner whereas serum yohimbine concentration was not significantly different 30 min after treatment with the 1 1 and 3 mg/kg doses regardless of the route of injection. Despite the fact that serum yohimbine concentration was 5-fold greater after i.v. injection as compared to s.c. administration (1 and 3 mg/kg doses), brain yohimbine concentrations were comparable after s.c. and i.v. injection and thus not dependent on either the route of administration or serum yohimbine concentration. The fact that the s.c. and i.v. injection of yohimbine lead to comparable dose-related increases in both brain yohimbine concentrations and neuroendocrine responses suggests that increased sympathetic outflow resulted primarily from an action of yohimbine at central, rather than peripheral, alpha 2-adrenoceptors. However, the data also are consistent with a purely peripheral prejunctional action of the 1 mg/kg dose and a combined central and peripheral action of the 3 mg/kg dose.

Captopril increases norepinephrine spillover rate in conscious spontaneously hypertensive rats.

These experiments were designed to test the hypothesis that the antihypertensive action of the converting enzyme inhibitor captopril in conscious spontaneously hypertensive rats is associated with an inhibition of norepinephrine release from peripheral sympathetic neurons. Radiotracer techniques were used to measure norepinephrine clearance and spillover rate into plasma. A single 30 mg/kg (s.c.) dose of captopril elevated norepinephrine spillover rate by 20 to 25 and 45 to 60% at 0.5- and 2-hr postinjection, respectively. At 2-hr postinjection, captopril (10 and 30 mg/kg s.c.) produced a dose-related fall in mean arterial pressure (MAP) and dose-related increase in norepinephrine spillover rate. The 30-mg/kg dose was more effective in decreasing MAP when given s.c. as compared to i.v. dosing. When equivasodepressor doses of captopril, hydralazine and prazosin were compared at 2-hr postinjection, the increases in norepinephrine spillover rate produced by captopril (44%) and hydralazine (68%) were not different. However, prazosin elevated norepinephrine spillover rate by 137%. Norepinephrine clearance was not altered by captopril. When MAP was lowered to the same extent (-17 to -23%) by 5 days of continuous treatment with captopril, enalaprilat and minoxidil, the increases in norepinephrine spillover rate (50-65%) were not different in the three treatment groups. In conclusion, these data do not support the hypothesis that captopril lowers blood pressure by inhibiting the neuronal release of norepinephrine.

Propranolol and atenolol inhibit norepinephrine spillover rate into plasma in conscious spontaneously hypertensive rats.

Radiotracer techniques capable of measuring norepinephrine clearance and spillover rate into plasma were used to test the hypothesis that the antihypertensive effects of propranolol and atenolol in conscious spontaneously hypertensive rats are associated with an inhibition of norepinephrine release from postganglionic sympathetic neurons. The 10%-15% fall in mean arterial pressure produced over 4 h by propranolol (1, 3.3 and 10 mg/kg, s.c.) and atenolol (1, 3.3 and 10 mg/kg, s.c.) was not dose-related, and only the largest dose of propranolol caused a significant bradycardia. Each dose of atenolol significantly lowered heart rate. The decrease in blood pressure caused by propranolol and atenolol was not related to the decrease in heart rate. Both propranolol and atenolol inhibited norepinephrine clearance by 12% to 16%. The 1 mg/kg doses of propranolol and atenolol significantly suppressed norepinephrine spillover rate by 21% and 32%, respectively, at 4 h postinjection. As the dose of propranolol was increased, the inhibition of norepinephrine spillover was reversed as plasma epinephrine concentration rose by 125%. The suppression of norepinephrine spillover rate caused by atenolol was more persistent but did diminish after the 10 mg/kg dose, when plasma epinephrine concentration was elevated by 55%. Both drugs suppressed plasma renin concentration, but the inhibition of norepinephrine spillover rate by propranolol and atenolol was not related to the fall in plasma renin concentration. By comparison, treatment with the adrenergic neuron blocking agent bretylium (5, 10, 20 and 40 mg/kg, s.c.) elicited a dose-related vasodepression with no change in heart rate or plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Pindolol increases plasma norepinephrine concentration by stimulation of beta 2-adrenoceptors in conscious spontaneously hypertensive rats.

The beta-adrenoceptor antagonist pindolol [10-1,000 micrograms/kg subcutaneously (s.c.)] caused dose-related decreases in mean arterial pressure (MAP) and increased heart rate (HR) in conscious spontaneously hypertensive rats (SHR). The lowest dose of pindolol (10 micrograms/kg) decreased MAP by 25 mm Hg (-16%) without affecting plasma norepinephrine (NE) or plasma renin concentration (PRC). However, higher doses of pindolol elicited dose-related increases in plasma NE concentration and PRC. Plasma epinephrine concentration was not altered by pindolol. The selective beta 2-adrenoceptor antagonist ICI 118,551 (3 mg/kg, s.c.) prevented the tachycardia but not the increase in PRC caused by 100 micrograms/kg pindolol. Treatment with ICI 118,551 completely eliminated the 45% increase in plasma NE elicited by 100 micrograms/kg of pindolol even though the decrease in MAP caused by this dose of pindolol was the same in the presence (-33 mm Hg) and absence (-34 mm Hg) of beta 2-adrenoceptor blockade. These results indicate that the vasodepressor action of pindolol in SHR does not result from an agonistic effect at postjunctional beta 2-adrenoceptors in the vasculature. In addition, the increases in plasma NE concentration produced by pindolol result from stimulation of beta 2-adrenoceptors. These beta 2-adrenoceptors may be located prejunctionally on sympathetic neurons.

The differential effects of prazosin and hydralazine on sympathoadrenal activity in conscious rats.

The ability of the vasodilator hydralazine and the alpha 1-adrenoceptor antagonist prazosin to increase sympathoadrenal outflow was compared by measuring plasma norepinephrine and epinephrine concentrations, norepinephrine clearance and norepinephrine spillover rate into plasma in conscious Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Even though the vasodepressor effect of 1 mg/kg (i.p.) of prazosin (-23 mm Hg) was significantly less than that caused by 1 mg/kg (i.p.) of hydralazine (-31 mm Hg) in normotensive rats, the increases in plasma norepinephrine concentration and norepinephrine spillover rate were significantly larger in prazosin-treated rats. In conscious SHR, 0.5 mg/kg (i.p.) of prazosin and 0.3 mg/kg (i.p.) of hydralazine lowered blood pressure to the same extent (-22 mm Hg), but prazosin again produced significantly larger increases in plasma norepinephrine concentration and norepinephrine spillover rate. Neither prazosin nor hydralazine affected norepinephrine clearance, and only prazosin elicited a significant rise in plasma epinephrine concentration. This differential effect of prazosin and hydralazine on sympathoadrenal activity is best explained by the differing effects of these drugs on venous return and thus the afferent activity of the cardiopulmonary baroreceptors.

The measurement of norepinephrine clearance and spillover rate into plasma in conscious spontaneously hypertensive rats.

The clearance of norepinephrine from plasma and the spillover rate of norepinephrine into plasma were determined in conscious unrestrained spontaneously hypertensive rats by measuring the concentrations of 3H-norepinephrine and norepinephrine in arterial plasma after 90 min of i.v. infusion with 3H-norepinephrine. In 50 conscious spontaneously hypertensive rats treated with saline (control animals), the following basal values were obtained: plasma norepinephrine concentration = 149 +/- 5 pg/ml; plasma epinephrine concentration = 61 +/- 4 pg/ml; norepinephrine clearance = 188 +/- 4 ml min-1 kg-1; and norepinephrine spillover rate = 27.5 +/- 0.8 ng min-1 kg-1. A significant portion of infused 3H-norepinephrine appeared to be cleared from the plasma by the uptake1 process, since desipramine decreased norepinephrine clearance by 32%. The vasodilating agents hydralazine and minoxidil produced dose-related increases in norepinephrine spillover rate and plasma norepinephrine concentration, but the percent increases in norepinephrine spillover rate exceeded the percent increases in plasma norepinephrine concentration because of concomitant increases in norepinephrine clearance, particularly after treatment with minoxidil. The increase in norepinephrine clearance caused by hydralazine and minoxidil probably resulted from the increase in cardiac output and resultant increase in hepatic and/or pulmonary blood flow. Adrenal secretion of norepinephrine did not appear to contribute to the elevation in norepinephrine spillover rate elicited by hydralazine and minoxidil. Chlorisondamine suppressed norepinephrine spillover rate by 77%, in association with a 70% decline in plasma epinephrine concentration, whereas bretylium lowered norepinephrine spillover rate by only 41%, with no change in plasma epinephrine concentration. The decrements in norepinephrine clearance caused by chlorisondamine (-23%) and bretylium (-15%) were more or less proportional to the magnitude of the vasodepression caused by these drugs. Both norepinephrine spillover rate and clearance fell in a dose-related fashion after treatment with clonidine. After treatment with the sympathoinhibitory agents chlorisondamine, bretylium and clonidine, the percent decreases in norepinephrine spillover rate always exceeded the percent decreases in plasma norepinephrine concentration. Based on these observations, we conclude that norepinephrine spillover rate provides a more accurate measurement of the activity of the peripheral sympathetic nervous system than does plasma norepinephrine concentration in conscious spontaneously hypertensive rats.

Perfused rat intestine for study of norepinephrine release.

Previous preparations for studying the neuronal release of norepinephrine (NE) employed relatively large vessels, nonsanguinous perfusates, and the preloading of [3H]NE. To study the stimulated release of endogenous NE and the responses of true resistance vessels, we developed a rat intestine preparation that is pump perfused with canine red blood cells suspended in bicarbonate buffer with 6% albumin. In a pentobarbital-anesthetized rat, the duodenum, colon, and cecum are extirpated to isolate the ileum vascularly. After the superior mesenteric artery and vein are cannulated, the perivascular nerves are isolated to stimulate the postganglionic sympathetic fibers. To evaluate the preparation, we stimulated the sympathetic fibers at 1-10 Hz with supramaximal pulses. Resistance changes were assessed by monitoring perfusion pressure, and the concentration of NE was assayed in the venous effluent by the single-isotope radioenzymatic method. During nerve stimulation, the increases in both resistance and NE release rate were frequency dependent. Repetitions of electrical stimulation yielded reproducible frequency-response curves. Pretreatment with phentolamine (10 microM) abolished the resistance response and enhanced stimulated NE release, which roughly tripled at 10 Hz. Phentolamine at smaller doses (1 microM) eliminated the resistance responses to stimulation but did not enhance NE release. Cocaine alone (30 microM) increased base-line resistance and unstimulated NE release. After cocaine pretreatment, phentolamine at 1 microM enhanced the stimulated NE release rate. We conclude that the isolated rat intestine contains postsynaptic alpha-adrenoceptors that mediate vasconstriction and prejunctional alpha 2-adrenoceptors that mediate the inhibition of NE release. Thus the rat intestine is a responsive preparation for studying the release of endogenous NE and noradrenergic neurotransmission.

The pharmacokinetic properties of yohimbine in the conscious rat.

We used high performance liquid chromatography with fluorescence detection to measure the concentration of yohimbine in serum and brain of conscious Sprague-Dawley rats at various times after the i.v. injection of 1 mg/kg of yohimbine. The serum concentration-time profile of yohimbine was biphasic with a rapid distribution phase (t1/2 alpha = 0.048 h) followed by a very slow elimination phase t1/2 beta = 16.3 h). The clearance of yohimbine was 11 ml/h.kg-1, and the volume of distribution was 259 ml/kg. Increasing doses (0.3, 1 and 3 mg/kg, i.v.) of yohimbine produced non-linear increases in serum yohimbine concentration. Yohimbine entered the brain rapidly (5,000 ng/g at 5 min after 1 mg/kg, i.v.) and disappeared from brain with a t1/2 beta of 7.7 h. In contrast to serum yohimbine concentration, increasing doses of yohimbine (0.3, 1 and 3 mg/kg) produced linear increases in brain yohimbine concentration, a phenomenon which is consistent with concentration-dependent binding of yohimbine to plasma proteins. The rapid entry of yohimbine into the brain, the slow rate of elimination of yohimbine from serum and brain and the linear relationship of brain yohimbine concentration as a function of dose should be taken into consideration whenever yohimbine is to be used as a probe of alpha 2-adrenoceptor function in vivo.

Angiotensin II contributes to blood pressure maintenance in conscious rats treated with yohimbine.

Yohimbine (1 mg/kg s.c.) produced significant and persistent increases in plasma renin concentration and plasma norepinephrine concentration in conscious rats, but mean arterial pressure (MAP) and heart rate were unchanged. The subsequent i.v. infusion of the angiotensin II receptor antagonist saralasin (100 micrograms/kg per min) caused a significant decrease (-17%) in MAP. We conclude that yohimbine-induced renin release, and the resultant rise in plasma angiotensin II concentration, prevents the decrease in MAP which would result from the blockade of vascular alpha-adrenoceptors by yohimbine.

Hypotensive effects of lesions of the rostral ventrolateral medulla in rats are anesthetic-dependent.

These studies were designed to determine if the hypotensive effects of bilateral electrolytic lesions of the rostral ventrolateral medulla are dependent on the type of anesthetic agent used. The lesions caused an immediate fall in mean arterial pressure (MAP) in rats anesthetized with urethane, alpha-chloralose or sodium pentobarbital. At 30 min after placement of the lesions, severe hypotension (MAP = 54 +/- 5 mm Hg) persisted in the rats anesthetized with urethane. However, 30 min after placement of the lesions, the MAP of rats anesthetized with alpha-chloralose or sodium pentobarbital was 87 +/- 9 mm Hg and 99 +/- 10 mm Hg, respectively. Subsequent transection of the cervical spinal cord produced a much greater decrease in MAP in rats anesthetized with alpha-chloralose and sodium pentobarbital as compared to rats anesthetized with urethane. Heart rate was significantly lower after placement of the lesions in all 3 groups. We conclude that the magnitude of the hypotensive effect caused by placement of lesions in the rostral ventrolateral medulla is anesthetic-dependent and that the rostral ventrolateral medulla is not the only area of the central nervous system capable of maintaining vasomotor tone.

Changes in plasma catecholamines and plasma renin activity during hypotension in conscious rats with lesions of the nucleus tractus solitarii.

The purpose of the present study was to examine the effects of lesions of the nucleus tractus solitarii on the reflex control of sympathetic activity and renin release in the conscious rat. Two doses of the arteriolar vasodilator hydralazine (0.3 and 1 mg/kg, i.v.) were used to activate reflexively the sympathetic nervous system in nucleus tractus solitarii lesion and control rats. Administration of 1 mg/kg of hydralazine to the control rats caused mean arterial pressure to fall from 120 +/- 2 mm Hg to 84 +/- 2 mm Hg and elicited an 11.2-fold increase in plasma renin activity and a 2.7-fold increase in plasma norepinephrine concentration. Administration of 0.3 mg/kg of hydralazine caused the arterial pressure of the lesion group to fall from 118 +/- 3 mm Hg to a comparable value of 85 +/- 4 mmg Hg, but plasma renin activity and plasma norepinephrine concentration did not rise significantly. However, administration of 1 mg/kg of hydralazine to the lesion group caused arterial pressure to fall from 128 +/- 6 mm Hg to 64 +/- 2 mm Hg, in association with a 12.4-fold increase in plasma renin activity and a 1.6-fold elevation in plasma norepinephrine concentration. Atenolol, a beta 1-adrenoceptor antagonist, blocked 70% of the rise in plasma renin activity caused by 1 mg/kg of hydralazine in both groups of rats. In addition, prior renal denervation also markedly attenuated the rise in plasma renin activity caused by hydralazine in the lesion group. Finally, electrical stimulation of the vagus nerves, which caused a large vasodepressor response in the control group, failed to lower the arterial pressure of the lesion group. Based on these observations, we conclude that in the conscious rat (1) nucleus tractus solitarii lesions eliminate the arterial baroreflexes as well as the cardiopulmonary baroreflex, and (2) severe hypotension induces sympathetically mediated renin release in the apparent absence of arterial and cardiopulmonary baroreflex function.

Neurohumoral interactions in conscious dehydrated rabbit.

The purpose of this study was to examine the role of angiotensin II (ANG II), arginine vasopressin (AVP), and neurogenic mechanisms in maintaining arterial pressure (MAP) in conscious water-deprived rabbits. Water deprivation produced marked increases in plasma renin activity and the concentration of AVP; however, plasma catecholamine concentrations were unchanged. Arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) was similar in water-replete and dehydrated animals. Administration of an ANG II receptor antagonist (ANG IIX) to water-deprived animals produced a small decrease in MAP but no significant changes in HR or mesenteric and hindquarters vascular resistances. Similarly, there was no significant effect on MAP, HR, or regional hemodynamics when dehydrated animals received an AVP-V1 antagonist (AVPX). RSNA increased by maximums of 61 and 43% in response to ANG IIX and AVPX, respectively. Combined administration of ANG IIX and AVPX produced significant decreases in MAP (-9 mmHg) and hindquarters resistance (-24%) and 117% and 23 beat/min increases in RSNA and HR, respectively. The effect on mesenteric resistance was variable; however, the response was generally a decrease. We conclude that ANG II and AVP pressor mechanisms are activated to sustain MAP in the dehydrated state. In contrast, the basal level and baroreflex control of sympathetic nervous system activity are unchanged from the water-replete state. However, activation of sympathetic nerve activity may become important in maintaining peripheral resistance when ANG II and AVP receptors are blocked in water-deprived animals.

The mechanism of yohimbine-induced renin release in the conscious rat.

These studies were designed to determine the role of the central nervous system, the sympathetic nervous system, the adrenal glands and the renal sympathetic nerves in yohimbine-induced renin release in conscious rats. Yohimbine (0.3-10 mg/kg, s.c.) caused time- and dose-related increases in plasma renin activity (PRA) and concentration (PRC) which were accompanied by time- and dose-related elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. Significant positive correlations were found between the increases in PRA and the increases in plasma NE and Epi concentrations caused by yohimbine, and propranolol (1.5 mg/kg, s.c.) blocked 90% of yohimbine (3 mg/kg, s.c.)-induced renin release. Over the entire spectrum of doses of yohimbine, the increases in PRA and plasma NE and Epi concentrations were positively correlated with the decreases in mean arterial pressure (MAP), but the y-intercept was positive in every case and the 1 mg/kg dose of yohimbine consistently increased PRA independent of any change in MAP. Complete renal denervation, as evidenced by a greater than 90% reduction in renal NE content, did not alter the increase in PRA caused by yohimbine (3 mg/kg, s.c.). An increase in circulating plasma catecholamine concentrations appeared to mediate yohimbine-induced renin release since propranolol prevented the rise in PRA caused by yohimbine in renal denervated rats. Prior adrenalectomy (Adx) also failed to prevent the rise in PRA produced by yohimbine (3 mg/kg, s.c.), but a combination of Adx and renal denervation caused a significant impairment of yohimbine-induced renin release. However, neither Adx alone nor the combination of Adx and renal denervation affected the increase in plasma NE concentration caused by yohimbine. Complete transection of the spinal cord at C8 caused a drastic reduction in plasma catecholamine concentrations but did not change basal PRC. Yohimbine (3 mg/kg, s.c.) did not increase PRC or plasma catecholamine concentrations after spinal transection. Based on these results, we conclude that 1) the stimulation of renin release by yohimbine is a secondary neurohormonal consequence of the generalized increase in sympathetic activity caused by yohimbine, 2) the sympathoadrenal activation produced by yohimbine results from an action in the brain which is amplified by the simultaneous blockade of prejunctional alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Parabrachial lesions increase plasma norepinephrine concentration, plasma renin activity and enhance baroreflex sensitivity in the conscious rat.

Electrolytic lesions of the parabrachial nucleus (PBN) caused significant increases in basal plasma renin activity (+433%) and basal plasma norepinephrine concentration (+98%) in conscious rats. Plasma epinephrine concentration, mean arterial pressure, heart rate, hematocrit, plasma osmolality and plasma sodium and potassium concentrations were not significantly affected by the lesions. Atenolol reduced the elevated plasma renin activity in the lesion group to a value similar to that of a control group (sham lesions or lesions in areas adjacent to the PBN). Captopril significantly lowered mean arterial pressure in the lesion group, but it had no effect on arterial pressure in the control group. Lesions of the PBN also increased the baroreflex-mediated bradycardia evoked by an abrupt elevation of arterial pressure. We propose that the PBN tonically inhibits sympathetic activity, sympathetically mediated renin release and baroreflex sensitivity.

Response of plasma norepinephrine concentration to the vasodepression caused by beta-adrenoceptor antagonists in the conscious spontaneously hypertensive rat.

The subcutaneous administration of a single dose of the beta-adrenoceptor antagonists atenolol, betaxolol, oxprenolol, pindolol, propranolol, or sotalol to conscious spontaneously hypertensive rats (SHR) lowered mean arterial pressure (MAP) by 15-20%, but this vaso-depression was not accompanied by a rise in plasma norepinephrine (NE) concentration. When MAP was decreased at the same rate and to the same extent with the vasodilator minoxidil, plasma NE concentration increased 50-75%. Atenolol, betaxolol, propranolol, and sotalol lowered heart rate, whereas oxprenolol, pindolol, and minoxidil elicited a tachycardia. Atenolol (-48%), betaxolol (-63%), and propranolol (-29%) significantly suppressed plasma renin activity (PRA), and minoxidil elevated PRA by 150-315%. Pindolol (+37%) caused a nonsignificant increase in PRA, and oxprenolol (-23%) and sotalol (-17%) produced nonsignificant decreases in PRA. Because the beta-adrenoceptor antagonists did not increase plasma NE concentration, whereas an equivasodepressor dose of minoxidil did, we conclude that plasma NE concentration is inappropriately low relative to the decrease in MAP caused by beta-adrenoceptor antagonists in the conscious SHR. In addition, the diverse effects of the beta-adrenoceptor antagonists on PRA in SHRs indicate that a suppression of renin release cannot account for either the decrease in MAP caused by these drugs or the failure of plasma NE concentration to increase when MAP is decreased by beta-adrenoceptor antagonists.

The response of plasma catecholamines to the vasodepression caused by beta-adrenoceptor antagonists in the spontaneously hypertensive rat.

The 15-20% decrease in mean arterial pressure (MAP) seen in conscious spontaneously hypertensive rats (SHR) after the administration of a single dose of the beta-adrenoceptor antagonists atenolol, betaxolol, oxprenolol, pindolol, propranolol or sotalol was not accompanied by an increase in plasma norepinephrine (NE) concentration. In marked contrast, plasma NE concentration increased by 50-75% when MAP was lowered at the same rate, and to the same extent with the vasodilator minoxidil. Atenolol, betaxolol and propranolol significantly suppressed plasma renin activity (PRA), whereas oxprenolol, pindolol and sotalol did not alter PRA significantly. Based on these observations, I conclude that beta-adrenoceptor antagonists impair the normal baroreflexly-mediated increase in plasma NE concentration which occurs in response to a decrease in MAP and this sympatho-inhibitory effect does not require the suppression of renin release.

The effect of propranolol on blood pressure and central MOPEG concentration in the conscious spontaneously hypertensive rat.

The total concentration of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethyl glycol (MOPEG) and propranolol concentration was measured in the medulla, pons, hypothalamus and thoracic spinal cord of conscious spontaneously hypertensive rats during the development of the antihypertensive effect of a single dose of d,l-propranolol (10 mg/kg s.c.). Propranolol significantly increased MOPEG concentration by 21% in the thoracic spinal cord (2 h) and 16% in the hypothalamus (4 h), but no consistent pattern of change in regional MOPEG concentration was found in relation to the time course of the antihypertensive effect of propranolol.

Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients.

To determine if clinically effective doses of the antihypertensive agent captopril affected the neuronal release of norepinephrine or baroreflex sensitivity, changes in plasma norepinephrine concentration and heart rate were related to the changes in mean arterial pressure seen during the intravenous infusion of stepwise incremental doses of sodium nitroprusside before and during captopril treatment in eight hypertensive men with normal or low plasma renin activity. At all times, significant linear correlations were found between the decrease in mean arterial pressure and the dose of sodium nitroprusside, the increase in heart rate and the decrease in mean arterial pressure, and the increase in plasma norepinephrine concentration and the decrease in mean arterial pressure. When the subjects were treated with captopril (25 mg t.i.d.) for 2 to 4 weeks, supine mean arterial pressure decreased from 130 to 114 mm Hg (-12%; p less than 0.05), heart rate did not change, supine and upright plasma renin activity increased, while supine plasma norepinephrine and epinephrine concentration decreased slightly. Therapy with captopril (25 mg t.i.d.) increased baroreflex sensitivity, as assessed by the slope of the regression line relating the increase in heart rate to the decrease in mean arterial pressure, and increased the responsiveness of the sympathetic nervous system, as assessed by the slope of the regression line relating the increase in plasma norepinephrine concentration to the decrease in mean arterial pressure. These increases were accompanied by a decrease in the slope of the regression line relating the decrease in mean arterial pressure to the dose of sodium nitroprusside and thus were associated with a decreased sensitivity to the vasodepressor effects of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular and neuroendocrine responses to behavioral stress after central or peripheral barodenervation in rats.

The cardiovascular and neuroendocrine responses to acute behavioral stress were evaluated in rats after disruption of the baroreflexes by electrolytic lesions of the nucleus tractus solitarii (NTS) or sinoaortic denervation (SAD). Rats with NTS lesions or SAD showed significantly greater increases in mean arterial pressure (MAP) and plasma norepinephrine (NE) concentrations than control rats during a single 30-min escape-avoidance test. In addition, the increases in MAP and plasma NE concentration of NTS lesion rats were significantly greater than those of SAD rats. However, NTS lesion rats showed no increase in plasma renin activity (PRA), as observed in the other groups. Thus, disruption of the baroreflexes by NTS lesions or SAD augments the arterial pressure and plasma NE responses to stress. Additionally, NTS lesions appeared to eliminate the neurons or fibers of passage participating in the sympathetically mediated increase in PRA.