vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Hypertension

The pressor action of vasopressin (AVP) in humans was investigated with the specific anti-vasopressor V1 antagonist d(CH2)5-O(Me)-Tyr-AVP. A single 0.5-mg intravenous bolus of this agent inhibited the pressor effect of AVP by about 80%. Normally hydrated humans had no blood pressure response to this dose, but this agent did prevent the blood pressure rise in response to exogenous AVP given in doses up to 200 milli-units/kg. Patients with severe hypertension, especially that associated with end-stage renal disease, tended to respond with moderate increases in blood pressure and plasma AVP after sodium overload and had a modest blood pressure fall (10-20 mmHg) in response to a single intravenous bolus of the AVP antagonist. Patients with an impaired sympathetic nervous system had increased sensitivity to the pressor action of AVP, in keeping with knowledge derived from experimental studies. These data suggest an interaction between AVP and alpha-adrenergic function, whereby the latter tends to attenuate the pressor action of AVP although it facilitates the release of AVP in response to various stimuli. In patients with congestive heart failure, the direct pressor action of AVP appears to contribute to increased systemic vascular resistance in about 30% of cases, i.e., those with plasma AVP concentrations well above the normal range. In these subjects, circulating AVP concentrations correlated with a decrease in vascular resistance in response to the V1 antagonist.

Topics: Animals; Arginine Vasopressin; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Sympathetic Nervous System; Vasopressins

The contribution of neurohumoral factors to arterial pressure has been studied in several models of sodium-dependent hypertension including the deoxycorticosterone-saline, Dahl salt-sensitive rats, and reduced renal mass-saline. Observations from these animals have largely pointed to the sympathetic nervous system and arginine vasopressin (AVP) as the critical factors responsible for mediating the increased arterial pressure. Our work has indicated that the one-kidney, figure-8 renal wrap model of experimental hypertension is also sodium dependent. In these rats, prior sodium depletion prevented the development of hypertension whereas high sodium intake exacerbated the increase in arterial pressure. An activation of the sympathetic nervous system and increased AVP activity appeared to be responsible for the hypertension in rats maintained on normal and high sodium intake. Stimulation of the AVP and sympathetic nervous systems in sodium-dependent hypertension may be associated with a suppression of cardiovascular gamma-aminobutyric acid (GABA)-ergic function in the central nervous system. The inhibitory neurotransmitter, GABA, and an inhibitor of GABA uptake, nipecotic acid, lowered arterial pressure in a sodium-stimulated model of hypertension.

Topics: Animals; Arginine Vasopressin; Diet, Sodium-Restricted; gamma-Aminobutyric Acid; Humans; Hypertension; Hypertension, Renal; Neurotransmitter Agents; Nipecotic Acids; Proline; Saline Solution, Hypertonic; Sodium

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate and skin blood flow was investigated in 8 untreated patients with mild essential hypertension using a specific antagonist of the pressor effect of AVP. Skin blood flow was measured with a laser Doppler flowmeter and blood pressure with a Remler M2000 recorder. The study was carried out in double-blind fashion using a cross-over design. Each patient received at a 60 min interval the AVP-antagonist, d(CH2)5Tyr(Me) AVP, 5 micrograms/kg i.v., and its vehicle. The sequence of treatment phases was randomly allocated. Pretreatment plasma AVP levels averaged 1.1 +/- 0.2 pg/ml (mean +/- SEM). Neither the AVP-antagonist nor its vehicle had any effect on blood pressure, heart rate and skin blood flow as well as on plasma renin activity and plasma catecholamines. It is therefore concluded that circulating AVP does not contribute to the maintenance of blood pressure in patients with mild essential hypertension and normal plasma AVP levels.

Topics: Adult; Arginine Vasopressin; Blood Pressure; Female; Heart Rate; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Osmolar Concentration; Regional Blood Flow

By examining vasopressin V1a receptor (V1aR) knockout (KO) mice, we previously found that the V1aR is critically involved in the regulation of normal blood pressure. The present study was undertaken to elucidate the role of the V1aR in salt-induced hypertension.. We compared haemodynamic responses induced by subtotal nephrectomy + salt loading in V1aR KO mice with those of wild-type (WT) controls. The time course of changes in the systolic blood pressure and heart rate during the salt loading was attenuated in the KO mice compared with that for the WT mice. The elevation of the plasma norepinephrine level caused by the subtotal nephrectomy + salt loading was also reduced in the V1aR KO mice. A V1aR antagonist markedly lowered the arterial blood pressure in the salt-loaded WT mice but not in the normotensive WT mice or in the salt-loaded or normotensive V1aR KO mice. Whereas arginine vasopressin (AVP) administered to the lateral ventricle of the brain induced pressor and tachycardiac responses accompanied by sympathetic activation in the WT mice, these events were completely abolished in the V1aR KO mice. Also, pressor and tachycardiac responses induced by intraventricularly administered hypertonic saline in the WT mice were diminished in the V1aR KO mice. Moreover, the pressor response induced by intraventricularly administered AVP was reduced in alpha(1d) adrenoceptor KO mice, whereas the tachycardiac response did not differ from that of the WT mice.. These results suggest that the V1aR is involved in the elevation of arterial blood pressure caused by dietary salt and that a V1aR antagonist, in particular regarding its effect in the brain, could have significant therapeutic potential in the treatment of hypertension.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Disease Models, Animal; Heart Rate; Hormone Antagonists; Hypertension; Injections, Intraventricular; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephrectomy; Receptors, Adrenergic, alpha-1; Receptors, Vasopressin; Saline Solution, Hypertonic; Sodium; Sodium Chloride, Dietary; Sympathetic Nervous System; Time Factors; Vasoconstriction

1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangemen

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Arginine Vasopressin; Baroreflex; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Ganglionic Blockers; Heart Rate; Hematocrit; Hexamethonium; Hormone Antagonists; Hypertension; Kidney; Losartan; Male; Nitroprusside; Organ Size; Peptidyl-Dipeptidase A; Phenylephrine; Rats; Rats, Wistar; Renin; Renin-Angiotensin System; Sodium Chloride, Dietary; Sympathetic Nervous System; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

To test the hypothesis that increased osmolality contributes to hypertension in deoxycorticosterone acetate (DOCA)-salt-hypertensive rats by acting in the brain, DOCA-salt and Sham-salt rats were instrumented with bilateral, nonoccluding intracarotid and femoral catheters. Two weeks prior, rats were uninephrectomized and received subcutaneous implants with or without DOCA (65 mg) and began drinking salt water (1% NaCl and 0.2% KCl). DOCA-salt rats (n=28) exhibited elevated blood pressure (159+/-4 mm Hg; P<0.05) and heart rate (392+/-10 bpm; P<0.05) compared with Sham-salt animals (n=5; blood pressure: 107+/-5 mm Hg; heart rate: 355+/-10 bpm). Bilateral intracarotid infusion of hypotonic fluid (osmolality: approximately 40 mOsm/L), which lowers osmolality of blood to the brain by approximately 2%, rapidly decreased blood pressure in DOCA-salt rats (-22+/-4 mm Hg after 15 minutes; P<0.05; n=7) but not Sham-salt rats (2+/-2 mm Hg; n=5). Hypotonic fluid infused intravenously did not lower blood pressure (0+/-2 mm Hg) in DOCA-salt rats (n=7). In DOCA-salt rats pretreated with a V(1) vasopressin antagonist (Manning compound, 5 microg, IV), intracarotid hypotonic infusion still decreased blood pressure (-10+/-3 mm Hg; P<0.05; n=9), but the response was smaller (P<0.05). Finally, in DOCA-salt rats (n=4) pretreated with the V(1) antagonist and the ganglionic blocker hexamethonium, decreasing osmolality of blood to the brain did not reduce blood pressure. These data indicate that, in DOCA-salt rats, hypertonicity acts in the brain to support blood pressure, in part by stimulating vasopressin secretion and in part by stimulating another rapidly reversible mechanism, likely the sympathetic nervous system.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Brain; Carotid Arteries; Desoxycorticosterone; Ganglionic Blockers; Hexamethonium; Hormone Antagonists; Hypertension; Hypotonic Solutions; Injections, Intra-Arterial; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Sodium Chloride

In normotensive Wistar rats, vasopressin may act as an excitatory neurotransmitter at synapses of paraventricular neurones on rostral ventrolateral medullary vasomotor neurones. We studied the influence of this neurotransmitter in spontaneously hypertensive rats to determine if it contributed to the increases in sympathetic nerve traffic in these rats.A five-barrel micropipette assembly was used for extracellular recording of neuronal activity and for microiontophoresis of drugs into the vicinity of identified medullary vasomotor neurones. Excitatory effects of iontophoretically applied vasopressin were blocked by simultaneous iontophoretic application of V(1a) antagonist. Similar application of the vasopressin receptor antagonist did not block an excitatory effect of iontophoretically applied glutamate. Excitatory effects produced by activating paraventricular neurones were also blocked by the V(1a) antagonist. However, the vasopressin antagonist did not alter the ongoing activity of medullary vasomotor neurones. Therefore, in these anaesthetised hypertensive rats, we concluded that vasopressin neurones do not exert a significant tonic drive to rostral ventrolateral medullary-spinal vasomotor neurones.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Cardiovascular System; Glutamic Acid; Hypertension; Iontophoresis; Medulla Oblongata; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Wistar; Sympathetic Nervous System; Vasoconstrictor Agents; Vasomotor System; Vasopressins

Acute electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) reduce blood pressure (BP) in SHR but not in normotensive Wistar-Kyoto and Wistar rats and abolish the pressor response to intravenous injection of potassium cyanide. We investigated the chronic effect of commNTS lesions on mean arterial pressure (MAP), and on baroreceptor and chemoreceptor reflex responses in SHR. The contribution of the sympathetic nervous system and the hormones vasopressin and angiotensin II to maintenance of BP in lesioned SHR was also investigated. MAP fell to normotensive levels the day after lesioning the commNTS but returned to the hypertensive level 9 days later. The reflex tachycardia evoked by sodium nitroprusside remained attenuated for 10 days after commNTS lesions but became enhanced 30 days after commNTS lesions. The pressor component of the chemoreflex elicited by potassium cyanide remained blocked for 30 days after lesions. Vasopressin antagonist or ACE blocker did not change MAP in sham or commNTS-lesioned SHR. Ganglionic blockade with hexamethonium elicited similar reductions in MAP in sham and commNTS-lesioned SHR. Results demonstrated that commNTS lesions in SHR produce a transient fall in BP and a long-lasting inhibition of the pressor response of the chemoreflex. Therefore, the blockade of the pressor response to peripheral chemoreflex activation is not sufficient to chronically reduce MAP in SHR. In the chronic absence of the commNTS, other subnuclei of the NTS or other brain stem nuclei may reorganize to replace the function of commNTS neurons, restoring sympathetic activity and high BP in SHR.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Baroreflex; Blood Pressure; Captopril; Chemoreceptor Cells; Electric Stimulation; Ganglionic Blockers; Heart Rate; Hexamethonium; Hypertension; Kinetics; Male; Rats; Rats, Inbred SHR; Solitary Nucleus

1. The relative roles of endothelin (ET) and vasopressin (AVP) in the regulation of blood pressure (BP), cardiac output (CO) and total peripheral resistance (TPR) were investigated in the early stages (24 - 31 days) of development of hypertension in the conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. 2. BP was recorded with radiotelemetry devices and CO with ultrasonic transit-time probes. TPR was calculated from the BP and CO recordings. The contributions of endogenous ET and AVP were studied by infusing [d(CH(2))(5)(1),O-Me_Tyr(2),Arg(8)]-vasopressin, a V(1)-receptor antagonist, and bosentan, a mixed ET(A)/ET(B) receptor antagonist (Study 1). Vascular responsiveness was estimated from the changes in TPR evoked by i.v. infusions of ET-1 and AVP (Study 2). 3. In study 1, infusion of bosentan reduced TPR and BP dramatically in DOCA-salt hypertensive rats but not in SHAM control rats, and this effect was greater when the AVP system had been blocked. In contrast, the V(1) receptor antagonist alone failed to change TPR and BP in DOCA-salt hypertensive rats. However, subsequent infusion of the V(1) receptor antagonist during the plateau phase of the response in bosentan pretreated DOCA-salt hypertensive rats led to significant decreases in both BP and TPR. 4. In study 2, TPR and BP responses to ET-1, but not AVP, were greater in DOCA-salt rats than in control rats. CO responses to ET-1 or AVP were similar in the two groups. 5. The results suggest that both ET and AVP play a role in the maintenance of TPR and BP; when one system is blocked the other compensates. However, the magnitude of the contribution to the hypertensive state appears greater for ET than for AVP. Enhanced vascular responses to ET appear to contribute to this greater role.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Bosentan; Cardiac Output; Desoxycorticosterone; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Hypertension; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley; Sulfonamides; Time Factors; Vascular Resistance; Vasopressins

We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 microg/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). In WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then returned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP and HR gradually decreased, reaching a nadir 20 min after injection. Five min after docarpamine, plasma dopamine and 3,4-dihydroxy phenyl acetic (DOPAC) levels increased in both WKY rats (n=5) and SHRs (n=5). The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the D1-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V1 (n=3) receptor blockade also abrogated the effects of docarpamine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpamine are mediated by D1-like receptors. In WKY rats, the pressor and tachycardiac responses are caused by an interaction among D1-like, alpha-adrenergic, and V1 receptors.

Topics: Adrenergic alpha-Antagonists; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Benzazepines; Blood Pressure; Catecholamines; Catechols; Dopamine; Dopamine Antagonists; Hormone Antagonists; Hypertension; Male; Phentolamine; Prodrugs; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Dopamine D1

We tested the hypothesis that hypertension in atrial natriuretic peptide (ANP) knockout mice is caused in part by disinhibition of angiotensin II-mediated vasopressin release. Inactin-anesthetized F(2) homozygous ANP gene-disrupted mice (-/-) and wild-type (+/+) littermates were surgically prepared for carotid arterial blood pressure measurement (ABP) and background intravenous injection of physiological saline or vasopressin V(1)-receptor antagonist (Manning compound, 10 ng/g body wt) and subsequent intracerebroventricular (left lateral ventricle) injection of saline (5 microl) or ANP (0.5 microg) or angiotensin II AT(1)-receptor antagonist losartan (10 microg). Only (-/-) showed significant decrease in ABP after intracerebroventricular ANP or losartan. Both showed significant hypotension after intravenous V(1) antagonist, but there was no difference between their responses. We conclude that 1) vasopressin contributes equally to ABP maintenance in ANP-disrupted mice and wild-type controls; 2) permanently elevated ABP in ANP knockouts is associated with increased central nervous angiotensin II AT(1)-receptor activation; 3) disinhibition of central nervous angiotensin II AT(1) receptors in ANP-deficient animals does not lead to a significant increase in the importance of vasopressin as a mechanism for blood pressure maintenance.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Hormone Antagonists; Hypertension; Injections, Intravenous; Losartan; Male; Mice; Mice, Knockout; Paraventricular Hypothalamic Nucleus; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Vasopressins

Arginine vasopressin (AVP), in addition to being an antidiuretic hormone, might also have pressor effects relevant to the maintenance of hypertension. Results from several experimental and clinical studies suggested that the pressor function of AVP is more important in low-renin hypertension and in the salt-loaded state and that it might be further maximized under sympathetic suppression.. To assess whether selective vasopressin receptor inhibition lowers the blood pressure in a racially diverse group of low-renin hypertensive subjects.. Thirty-nine hypertensive subjects (16 Caucasian, 23 African-American) eating a 200 mmol/day sodium diet were administered a single intravenous dose of a selective vasopressin receptor antagonist and their blood pressure was monitored constantly for the ensuing 3 h. The protocol was repeated 3 days later after treatment with a single oral dose of 0.4 mg clonidine.. Of these patients, 54% had their blood sampled for determination of hormone profiles. African-Americans with hypertension had higher baseline plasma AVP levels than did Caucasians (1.13 +/- 0.05 versus 0.37 +/- 0.06 pg/ml, respectively, P < 0.05), and lower plasma renin activity (0.34 +/- 0.07 versus 1.03 +/- 0.08 ng/ml per h, respectively, P < 0.05). Selective vasopressin receptor inhibition lowered the mean arterial pressure in African-Americans but not that in Caucasians (lowering by 28 +/- 4 mmHg in African-Americans versus lowering by 5 +/- 3 mmHg in Caucasians, P < 0.05). Moreover, vasopressin receptor blockade further reduced the arterial pressure in African-Americans but not that in Caucasians after pretreatment with clonidine.. AVP seems to play a more important role as a pressor hormone in maintaining the elevation of arterial pressure in African-American hypertensives than it does in Caucasian hypertensives.

Topics: Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Black People; Blood Pressure; Female; Hormone Antagonists; Humans; Hypertension; Kidney; Male; Middle Aged; Renin; White People

We investigated the genesis of the hypertensive response to acute (45 min) aortic constriction in two models of chronic vasopressin (AVP) deficiency, i.e., Brattleboro strain and median eminence lesioned (MEL) Wistar rats. The same degree of partial aortic constriction, with a pneumatic cuff placed around the abdominal aorta, yielded a sudden and maintained increase in carotid pressure to the same extent in Brattleboro, MEL and sham-MEL rats. Blockage of AVP V1 receptors with d(CH2)5Tyr[Me]AVP did not affect the hypertensive response of Brattleboro or MEL rats, but gradually blunted the response of sham-MEL rats. Blockage of angiotensin II receptors with saralasin blunted the hypertensive response of the AVP-deficient subjects throughout the experiment, but only delayed (5-15 min) the onset of hypertension in sham-MEL rats. Simultaneous blockage of AVP and angiotensin II blunted the hypertensive response of sham-MEL and AVP-deficient rats throughout the experiment. These data demonstrate that when one vasoactive system is chronically absent, as is the case for AVP in Brattleboro and MEL rats, the renin-angiotensin system plays the major role in the pathophysiology of acute aortic coarctation hypertension.

Topics: Angiotensin Receptor Antagonists; Animals; Antidiuretic Hormone Receptor Antagonists; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Chronic Disease; Female; Hormone Antagonists; Hypertension; Male; Median Eminence; Rats; Rats, Brattleboro; Rats, Wistar; Renin-Angiotensin System; Saralasin

The present study was designed to investigate the effect of a lack of vasopressin resulting from electrolytic lesion of the median eminence of the hypothalamus on the acute 45-min aortic coarctation hypertension elicited in conscious rats by means of a pneumatic cuff placed around the aorta above the renal arteries. Forty-eight hours after lesion, aortic constriction elicited a prompt (5-min) rise in mean carotid pressure from 115 +/- 2 to 149 +/- 2 mmHg, followed by a gradual decline to 129 +/- 2 mmHg. In contrast, sham-lesioned rats exhibited a prompt hypertensive response from 118 +/- 2 to 157 +/- 2 mmHg that leveled off throughout the experiment. Lesioned rats treated with saralasin presented a blunted hypertensive response (within 125 +/- 2 to 130 +/- 2 mmHg), whereas sham-lesioned rats showed only a delay in the onset of hypertension. The hypertensive response of lesioned rats was unaffected by the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP, whereas sham-lesioned rats submitted to this treatment presented a prompt rise in pressure followed by a gradual decline at the end of the experiment. Lesioned and sham-lesioned rats treated with saralasin plus vasopressin antagonist showed a blunted hypertensive response throughout the experiment. These data demonstrate that the integrity of the median eminence plays a pivotal role in the maintenance (30-45 min) of acute aortic coarctation hypertension, presumably involving the release of vasopressin from the neurohypophysis, whereas angiotensin II mainly accounts for the prompt (5-15 min) rise in pressure.

Topics: Acute Disease; Animals; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Hypertension; Male; Median Eminence; Rats; Rats, Wistar; Saralasin; Vasopressins

Effects of intracerebroventricular (third ventricle) injection of N-methyl-D-aspartate (NMDA) on arterial blood pressure, on heart rate, on arginine vasopressin (AVP) and levels of catecholamines in plasma and on the behaviour of normotensive freely-moving rats have been evaluated. N-Methyl-D-aspartate significantly (P less than 0.01) increased arterial blood pressure and levels of catecholamines and AVP in plasma. With 0.1-1.0 micrograms/rat all animals presented psychomotor agitation, stereotyped movements, hyperexcitability, exophthalmus, dyspnoea, jumping, rearing and teething. The selective antagonist for NMDA receptors, 2-APV injected in the third ventricle, significantly (P less than 0.01) antagonized the hypertension, the increase in levels of catecholamines and AVP in plasma and behavioural effects. An antagonist of alpha 1 adrenergic receptors, prazosin (i.v.), an agonist of alpha 2 adrenergic receptors, clonidine (i.c.v.) and a relatively selective antagonist of V1 subtype of receptor of AVP, CGP 25838 (i.c.v. and i.v.), 15 min before NMDA, significantly (P less than 0.01) decreased the effects induced by the injections of NMDA. On the contrary, an antagonist of opiate receptors, naloxone (i.v.), 15 min before NMDA, significantly (P less than 0.01) increased the NMDA-induced modifications. Pretreatment with the antagonists at these doses, did not significantly modify the basal values of arterial blood pressure and behaviour. Only 2-APV sometimes induced ataxia, lasting about 5 min. This study points out an increase in the central sympathetic efferent activity and in release of AVP involved in the NMDA-induced cardiovascular and behavioural effects.

Topics: 2-Amino-5-phosphonovalerate; Animals; Arginine Vasopressin; Blood Pressure; Cerebral Ventricles; Clonidine; Dose-Response Relationship, Drug; Epinephrine; Heart Rate; Hypertension; Injections, Intravenous; Injections, Intraventricular; Male; N-Methylaspartate; Naloxone; Norepinephrine; Prazosin; Rats; Rats, Inbred Strains

The hemodynamic responses and the role of renal nerves in the physiopathogenesis of acute (45 min) aortic coarctation hypertension were studied in conscious rats. The hemodynamic responses elicited by aortic constriction in intact and bilaterally nephrectomized rats were analyzed by means of miniaturized pulsed-Doppler flow probes. Anephric rats presented a smaller increase in mean carotid pressure (MCP) and calculated aortic resistance during aortic coarctation than did intact animals. Reflex bradycardia throughout the experiment did not differ significantly between the two groups. The pressor response following aortic coarctation in untreated renal-denervated rats was similar to that found in intact subjects. Renal-denervated rats previously treated with V1-vascular arginine vasopressin antagonist [d(CH2)5Tyr(Me)AVP] showed the same hypertensive response as control renal-denervated rats. Previous treatment of renal-denervated rats with saralasin (an angiotensin II antagonist) produced a significant reduction in the hypertensive response throughout the experiment when compared to untreated renal-denervated rats. Similarly, rats treated with the vasopressin antagonist plus saralasin showed a blunted hypertensive response following aortic coarctation. The results for rats previously treated with vasopressin antagonist plus saralasin did not differ from those obtained with saralasin alone. Overall, the results of aortic coarctation hypertension obtained in the present study indicate that: 1) Anephric rats showed a blunted hypertensive response due to the lack of neuro-humoral release of vasopressor substances (e.g. angiotensin II and vasopressin) triggered by the kidneys, when only the mechanical factor of constriction was present; 2) The lack of afferent feedback from the kidneys in renal-denervated rats for vasopressin release from the central nervous system allowed angiotensin II to play the major physiopathological role associated with the mechanical factor in the hypertensive response.

Topics: Animals; Aorta, Abdominal; Aortic Coarctation; Arginine Vasopressin; Denervation; Hemodynamics; Hypertension; Kidney; Male; Nephrectomy; Neurons, Afferent; Rats; Rats, Inbred Strains; Saralasin

To elucidate the contributions of renal, humoral, and arterial baroreceptor reflex components to salt-induced hypertension, we administered 10% NaCl intravenously for 10 days to sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7), sinoaortic-denervated rabbits with intact kidneys (n = 7), and sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7). Serial changes in mean arterial pressure (MAP), heart rate, and blood pressure variability were recorded. In sinoaortic-denervated rabbits with unilateral nephrectomy, MAP increased significantly from 109 +/- 2 to 124 +/- 3 mm Hg (day 4) and remained elevated for the rest of the experiment. This elevation of MAP was accompanied by a reduction in the standard deviation of MAP, with significant elevations in plasma vasopressin, norepinephrine, and atrial natriuretic peptide concentrations and in sodium retention. In the other groups, there were no significant changes in these vasoactive hormones. In the sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy, sodium retention was similar to that of sinoaortic-denervated rabbits with unilateral nephrectomy. Continuous infusion (1 microgram/kg/hr) of a V1 antagonist prevented the elevation of blood pressure and plasma norepinephrine, the accumulation of sodium, and the reduction of blood pressure lability, whereas a bolus injection (10 micrograms/kg) on day 4 reduced blood pressure from 128 +/- 3 to 115 +/- 2 mm Hg (p less than 0.005). These results imply that vasopressin plays a crucial role in the expression of salt-induced hypertension in rabbits with compromised baroreceptor and renal function.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Denervation; Endocrine Glands; Female; Heart; Heart Rate; Hypertension; Nephrectomy; Pressoreceptors; Pressure; Rabbits; Sodium; Sodium Chloride; Vasopressins

The role of vasopressin (AVP) and angiotensin II (ANG II) in the onset of acute (45 min) aortic coarctation hypertension was studied in conscious rats. Changes in mean carotid pressure (MCP) and heart rate (HR) were measured in four groups of rats. Control rats presented a hypertensive response that attained a plateau 5 min after coarctation and remained near this level throughout the experiment. Rats treated with AVP V1-vascular receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5Tyr(Me)AVP] presented a prompt rise in MCP similar to the control rats, but in contrast to this group, the MCP started to decline progressively. Rats treated with saralasin presented a delay in the onset of hypertension right after coarctation but slowly attained values similar to those for control rats. In contrast, the rats treated with AVP antagonist plus saralasin showed a blunted MCP elevation throughout the experiment. Reflex bradycardia observed in the rats treated with saralasin or the AVP antagonist plus saralasin was similar to that observed in the control rats, whereas for the group treated only with AVP antagonist, the reflex bradycardia was more intense than for the other three groups, indicating an increased sensitivity of the baroreflex. These data demonstrate that in addition to the mechanical effect of aortic constriction, both ANG II and AVP participate in the onset of acute aortic coarctation hypertension. Moreover, the results indicate that ANG II acts on the prompt (5 min) rise in pressure, whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation.

Topics: Acute Disease; Angiotensin II; Animals; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Carotid Arteries; Heart Rate; Hypertension; Male; Rats; Rats, Inbred Strains; Saralasin; Vasopressins

1. In conscious rabbits, intravenous morphine caused hypertension, bradycardia, hyperglycaemia and increased plasma adrenaline and noradrenaline. These effects were prevented by ganglionic blockade with pentolinium. 2. The cardiovascular responses to morphine were not altered by pretreatment with a vasopressin V1-receptor antagonist. 3. After bilateral adrenalectomy morphine caused a similar rise in noradrenaline but no increase in adrenaline. The rise in blood pressure was attenuated and the hyperglycaemia was abolished. 4. Adrenaline infused intravenously to mimic the levels that occurred after morphine caused a similar degree of hyperglycaemia but only a small increase in blood pressure. 5. Pretreatment with intracerebroventricular naloxone prevented the morphine-induced hypertension, hyperglycaemia, increase in plasma catecholamines, respiratory depression and sedation. 6. These results demonstrate that, in conscious rabbits, intravenous morphine causes hypertension by increasing sympathetic vasoconstrictor nerve activity and elevating plasma adrenaline levels; the latter alone produces the hyperglycaemia. Vasopressin release is not involved in the hypertensive response to morphine. The effects of morphine appear to result from stimulation of central opiate receptors leading to enhanced sympathoadrenal outflow.

Topics: Adrenalectomy; Animals; Arginine Vasopressin; Blood Pressure; Epinephrine; Heart Rate; Hypertension; Infusions, Intravenous; Injections, Intraventricular; Male; Morphine; Naloxone; Norepinephrine; Pentolinium Tartrate; Rabbits; Sympathetic Nervous System

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Topics: Animals; Arginine Vasopressin; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Bradycardia; Carbachol; Cardiovascular Physiological Phenomena; Cardiovascular System; Deamino Arginine Vasopressin; Hypertension; Injections, Intraventricular; Male; Nicotine; Parasympatholytics; Phentolamine; Physostigmine; Rats; Rats, Brattleboro; Vasopressins

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)

Topics: Animals; Arginine Vasopressin; Blood Pressure; Heart Rate; Hypertension; Kidney; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Renin; Vasopressins; Water-Electrolyte Balance

Our previous finding that dexamethasone-induced hypertension in rats is associated with enhanced reactivity of mesenteric arteries to arginine vasopressin but not to angiotensin II (Ang II) or norepinephrine has led us to postulate that vasopressin contributes to the development or maintenance of glucocorticoid-induced hypertension. To test this view, we investigated the effects of vasopressin, Ang II, norepinephrine, and the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP on mean arterial blood pressure and heart rate with and without ganglionic blockade with hexamethonium and angiotensin I (Ang I) converting enzyme inhibition with MK 421 in pentobarbital-anesthetized rats made hypertensive by treatment with dexamethasone (1.8 mg/kg/wk for 14 days). Administration of vasopressin, Ang II, or norepinephrine (0.003-3 microgram i.v.) produced a dose-related increase in arterial blood pressure. The pressor response to vasopressin, but not to Ang II or norepinephrine, was greater in dexamethasone-treated than in vehicle-treated animals, and this difference became more pronounced in rats that received hexamethonium and MK 421. Administration of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced arterial pressure in dexamethasone-treated but not in vehicle-treated animals. Hexamethonium and MK 421 reduced arterial blood pressure in dexamethasone-treated as well as in vehicle-treated rats; however, arterial blood pressure remained higher in the former. Administration of the vasopressin V1 receptor antagonist produced a greater reduction in arterial blood pressure in dexamethasone-treated than in vehicle-treated rats. These data suggest that vasopressin contributes to glucocorticoid-induced hypertension, which is probably due to enhanced vascular reactivity to the peptide.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Blood Pressure; Dexamethasone; Heart Rate; Hypertension; Male; Norepinephrine; Pressoreceptors; Rats; Rats, Inbred Strains; Receptors, Vasopressin

Experiments were conducted in conscious rats to determine whether DOCA-salt treatment could cause an elevation of sodium concentration of cerebrospinal fluid (CSF), which may be responsible for the enhanced activity of sympathetic nervous system (SNS) and increased secretion of vasopressin (AVP). Systolic blood pressure (SBP) and mean arterial pressure (MAP) were gradually but consistently increased by DOCA-salt treatment. Serum Na concentration was similarly increased with time by DOCA-salt, and significantly higher than control in the 4th treatment week. In contrast, DOCA-salt did not alter the CSF Na levels at any time during treatment. A relationship between SBP and CSF Na was never evident at any stage of the DOCA-salt hypertension. The decrease in MAP following administration of the vasopressin V1-receptor antagonist, d(CH2)5Tyr(Me)AVP (30 micrograms/kg), or hexamethonium (30 mg/kg) was enhanced in the DOCA-treated rats, as compared to findings in the controls. These hypotensive effects were gradually, but progressively enhanced with the development of hypertension by DOCA-salt treatment. We tentatively conclude that mechanisms accounting for the enhanced activity of SNS and AVP in DOCA-salt hypertensive rats are independent of an increased Na concentration in the CSF.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Hexamethonium Compounds; Hypertension; Male; Rats; Rats, Inbred Strains; Sodium

We evaluated the time course of changes in the relative contribution of arginine-vasopressin (AVP) and sympathetic nervous system (SNS) during the development of DOCA-salt hypertension in rats. Intravenous administrations of an AVP antagonist (d(CH2)5Tyr(Me) AVP; AVPA) and hexamethonium (C6) were given at 3 and 7 days, and 2 and 4 weeks after the initiation of treatment with DOCA-salt to conscious and unrestrained rats. Mean arterial pressure (MAP) was higher and heart rate (HR) tended to be rapid in the rats on DOCA-salt treatment for over 1 week, compared with those of the control groups. The hypotensive effect of AVPA in the DOCA-salt treated rats was gradually enhanced with the development of hypertension and was significantly greater than in the control rats, at all stages of hypertension, including the prehypertensive phase. The depressor response to intravenous C6 following AVPA also resulted in a gradual enhancement, with time, after DOCA treatment. This decrease in MAP was greater at the hypertensive stage than that in the control rats, although the response was not significantly different among three groups on the 3rd treatment day. It was concluded that the pressor systems AVP and SNS may contribute to the initiation and development as well as maintenance of DOCA-salt hypertension in rats.

Topics: Animals; Antihypertensive Agents; Arginine Vasopressin; Desoxycorticosterone; Hypertension; Male; Nephrectomy; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Sodium Chloride; Sympathetic Nervous System

The purpose of the present study is to determine whether DOCA-salt treatment could cause an elevation of Na concentration of cerebrospinal fluid (CSF), which may increase blood pressure (BP) as a result of enhanced activity of sympathetic nervous system (SNS) and vasopressin (AVP). Blood pressure was gradually increased by DOCA-salt treatment. Serum NA was also elevated with time by DOCA-salt, and significantly higher in DOCA rats on the 4th treatment week, as compared with controls. By contrast, DOCA-salt did not alter CSF Na at any time of treatment. No relationship was detected between BP and CSF Na at any stage of DOCA-salt hypertension. The precent fall in BP by AVP antagonist or hexamethonium was always greater in DOCA-treated rats than that in the controls. These hypotensive effects were gradually, but consistently enhanced with the development of hypertension in DOCA rats. It is concluded that the enhanced activity of both SNS and AVP system responsible for DOCA-salt hypertension may be attributed to the mechanism(s) unrelated to the increased CSF Na concentration.

Topics: 18-Hydroxycorticosterone; Adrenalectomy; Aldosterone; Animals; Arginine Vasopressin; Blood Pressure; Corticosterone; Hypertension; Rats; Rats, Inbred SHR

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)

Topics: Animals; Arginine Vasopressin; Blood Pressure; Hypertension; Male; Rats; Rats, Inbred SHR; Receptors, Angiotensin; Receptors, Vasopressin; Renin-Angiotensin System; Teprotide; Vasopressins

To investigate the role of arginine vasopressin (AVP) in the maintenance of blood pressure in deoxycorticosterone (DOC)-salt hypertension, the effects of specific pressor and antidiuretic antagonists of AVP were studied in conscious, freely moving rats with established malignant DOC-salt hypertension. Plasma AVP level was significantly higher in hypertensive than in normotensive animals (4.8 +/- 1.0 vs. 2.0 +/- 0.3 fmol/ml, n = 5, P less than 0.02). Administration of d(CH2)5-d-Leu-VAVP, 10 micrograms/kg, an AVP antagonist that blocked the antidiuretic, but not the pressor effect of exogenous AVP, induced diuresis, and caused a transient fall in blood pressure from 173 +/- 3 to 167 +/- 4 mmHg (n = 8, P less than 0.01) with a concomitant slight increase in heart rate. Similar changes were observed after administration of d(CH2)5Tyr(Et)VAVP, 10 micrograms/kg, an antidiuretic plus pressor antagonist of AVP. Intravenous injection of d(CH2)5Tyr(Me)AVP, 10 micrograms/kg, a specific AVP pressor antagonist had no effect on blood pressure or heart rate, although it completely abolished the pressor response to exogenous AVP. Plasma renin activity remained suppressed following administration of all AVP antagonists. These findings suggest that if AVP should contribute to maintaining high blood pressure in malignant DOC-salt hypertension it would have to be the results of its antidiuretic and not its vasoconstrictor property.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Female; Heart Rate; Hypertension; Rats; Rats, Inbred Strains

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate, and skin blood flow was assessed in normotensive subjects, mild hypertensive patients, and patients with congestive heart failure, utilizing the specific antagonist of AVP at the vascular receptor level, d(CH2)5Tyr(Me)AVP (5 micrograms/kg i.v.). The renin system of the normal volunteers treated with the AVP antagonist was either intact or acutely blocked with the angiotensin converting-enzyme inhibitor captopril (25 mg p.o.). In some volunteers, the cardiovascular effect of AVP released by Finnish sauna or cigarette smoking was studied. In patients with congestive heart failure, hemodynamic measurements (pressures and cardiac output) were obtained invasively. Acute blockade of AVP vascular receptors produced no cardiovascular effect unless plasma AVP levels were markedly elevated. In our experience, abnormally high circulating AVP appears to be responsible for the decrease in skin blood flow induced by cigarette smoking and to some extent for the maintenance of vascular tone in the rare patients with particularly severe congestive heart failure.

Topics: Angiotensin II; Arginine Vasopressin; Heart Failure; Hemodynamics; Humans; Hypertension; Smoking; Steam Bath; Vasopressins

A central pressor effect of angiotensin II (ANG II) has been implicated in the pathogenesis of several forms of experimental hypertension. Therefore, the present studies were designed to investigate mechanisms that contribute to hypertension resulting from selective stimulation of brain ANG II receptors by chronic intracerebroventricular (ICV) infusion of ANG II. Specifically, the role of the sympathetic nervous system, the pressor actions of vasopressin, and the direct vasoconstrictor effect of blood-borne ANG II were investigated in rats made hypertensive by 5- to 7-day ICV ANG II infusions (6 micrograms/h). Rats were chronically instrumented with indwelling arterial and venous catheters and a lateral cerebral ventricular cannula. Acute intravenous infusion of the competitive ANG II receptor antagonist [Sar1-Ala8]ANG II during the period of ICV ANG II infusion resulted in a moderate decrease in arterial pressure, indicating that an increase in blood-borne ANG II may account for a small component of the hypertensive response to ICV ANG II. Activation of the sympathetic nervous system appeared to be the major contributor to the elevated arterial pressure, since acute ganglionic blockade and combined alpha- and beta-adrenergic blockade produced greater depressor responses in rats made hypertensive with chronic ICV ANG II infusion than in normotensive rats. Furthermore, peripheral sympathectomy delayed hypertension development. Intravenous administration of a specific antagonist of the vascular vasopressin receptor did not cause a depressor response in rats made hypertensive with chronic ICV ANG II infusions. These studies demonstrate that a major mechanism involved in the pressor response to acute ICV ANG II injections, namely vasopressin release, does not appear to contribute to hypertension produced by chronic ICV infusions of ANG II. Rather, this form of hypertension is characterized predominantly by an increase in sympathetic vasoconstrictor tone and possibly by a mechanism activated by a small increase in circulating levels of ANG II.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Blood Pressure; Blood Vessels; Electric Stimulation; Ganglionic Blockers; Hexamethonium; Hexamethonium Compounds; Hypertension; Injections, Intraventricular; Male; Neurotransmitter Agents; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Saralasin; Spinal Cord; Sympathectomy, Chemical