Conscious Hypertensive Rats Research Articles

Suppression of a somatosympathetic reflex by the gamma-aminobutyric acid agonist muscimol and by clonidine.

gamma-Aminobutyric acid (GABA) and GABA agonists, e.g., muscimol, reduce blood pressure and sympathetic outflow and inhibit the "carotid occlusion reflex." In contrast, muscimol exerted only marginal effects on postural reflexes in a prior study. The somatosympathetic reflex, i.e., potentials evoked in sympathetic nerves in response to sensory nerve stimulation, is a useful model for studying centrally acting drugs. Effects of muscimol on the reflex were examined in anesthetized normotensive rats. At doses which had previously been shown to reduce blood pressure but to produce only minimal attenuation of postural reflexes in conscious hypertensive rats, muscimol, administered intracerebroventricularly, reduced blood pressure and inhibited the somatosympathetic reflex in the present study. The time course of the evoked potential was not altered. Baroreceptor activation and intracerebroventricular clonidine also suppressed the reflex. The inhibitory effect of muscimol but not that of clonidine was prevented by pretreatment with the GABA antagonist bicuculline. Thus, the marked suppression of the somatosympathetic reflex by muscimol and by clonidine, in contrast to minimal effects on postural reflexes, point to the selectivity of their central inhibitory actions.

Blood pressure overshoot under pentobarbitone anaesthesia following a single dose of clonidine in rats.

1. Withdrawal of chronic antihypertensive therapy with clonidine is known to produce a blood pressure overshoot. It has been reported that the same may occur after a single dose of clonidine. 2. A single, intramuscular dose of clonidine (0.05 mg/kg) produced an overshoot in blood pressure, on the day following administration, in normotensive rats anaesthetized with sodium pentobarbitone. 3. No rebound elevation of mean arterial pressure or of heart rate occurred in conscious, normotensive, spontaneously hypertensive or renal hypertensive rats following this dose of clonidine, nor did it occur in rats anaesthetized with ether. 4. It is suggested that the overshoot phenomenon in rats under barbiturate anaesthesia may involve an interaction between an effect of clonidine and the barbiturate.

Investigations into the pharmacological effects of spongiatriol.

Acute intraperitoneal doses of spongiatriol, a compound extracted from marine sponges, caused blood pressure but not heart rate to fall in conscious hypertensive rats in a dose-dependent manner up to 50 mg/kg at which dose mean blood pressure fell 24%. Diarrhoea also resulted. Chronic oral doses (50 mg/kg every 3 h) lowered blood pressure by 73 mmHg after 48 h in conscious hypertensive rats and caused severe diarrhoea. Spongiatriol was an atrial stimulant in vitro and this effect could be greatly reduced by prior reserpinization or by beta-adrenoceptor blockade. In anaesthetized cats spongiatriol (50 mg/kg i.p.) caused reductions in blood pressure (19%), heart rate (11%) and cardiac output (12%). Spongiatriol 10(-5) g/ml had no effect on the response to noradrenaline in isolated rat tail arteries, markedly inhibited the response of in vitro guinea-pig ilea to acetylcholine and had a slight potentiating effect on the response of in vitro rat fundus stomach to serotonin and prostaglandin E2.

Chemical Renal Medullectomy; Effect upon Reversal of Two-Kidney, One-Clip Hypertension in the Rat

1. Chemical renal medullectomy was produced in rats by injection of 2-bromoethylamine hydrobromide. Plasma creatinine and blood pressure were unchanged although urine volume was increased fourfold. 2. Left renal artery constriction resulted in similar degrees of hypertension in both intact and medullectomized rats. This was associated with a significantly smaller rise in plasma renin concentration in the latter. 3. Blood pressure in conscious intact hypertensive rats became normal within 24 h of unclipping whereas blood pressure of medullectomized rats remained significantly elevated. 4. The presence of an intact renal medulla is essential to the complete reversal of two-kidney, one-clip hypertension in the rat. This may reflect the loss of a medullary vasodepressor system.

Mechanoelastic properties of the aorta in chronically hypertensive conscious rats.

HomeHypertensionVol. 3, No. 6_pt_2Mechanoelastic properties of the aorta in chronically hypertensive conscious rats. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBMechanoelastic properties of the aorta in chronically hypertensive conscious rats. L C Michelini and E M Krieger L C MicheliniL C Michelini Search for more papers by this author and E M KriegerE M Krieger Search for more papers by this author Originally published1 Nov 1981https://doi.org/10.1161/01.HYP.3.6_Pt_2.II-177Hypertension. 1981;3 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Koike M, Moreira E, Da Silva G, Consolim-Colombo F, Ida F, Irigoyen M and Krieger E (2006) RESETTING OF AORTIC BARORECEPTORS IN RESPONSE TO HYPOTENSION DOES NOT ALTER GAIN SENSITIVITY, Clinical and Experimental Pharmacology and Physiology, 10.1111/j.1440-1681.2006.04431.x, 33:8, (679-684) Irigoyen M and Krieger E (1998) Baroreflex control of sympathetic activity in experimental hypertension, Brazilian Journal of Medical and Biological Research, 10.1590/S0100-879X1998000900015, 31:9, (1213-1220), Online publication date: 1-Sep-1998. Moreira E, Ida F and Krieger E (1990) Reversibility of baroreceptor hyposensitivity during reversal of hypertension., Hypertension, 10.1161/01.HYP.15.6.791, 15:6_pt_2, (791-796), Online publication date: 1-Jun-1990. Moreira E, Ida F, Oliveira V and Krieger E (1990) Rapid resetting of the baroreceptors in renal hypertensive rats., Hypertension, 10.1161/01.HYP.15.2_Suppl.I40, 15:2_supplement, Online publication date: 1-Feb-1990. Krieger E (1989) ARTERIAL BARORECEPTOR RESETTING IN HYPERTENSION (The J. W. McCubbin Memorial Lecture), Clinical and Experimental Pharmacology and Physiology, 10.1111/j.1440-1681.1989.tb02992.x, 16:s15, (3-17), Online publication date: 1-Jun-1989. November 1981Vol 3, Issue 6_pt_2 Advertisement Article InformationMetrics Copyright © 1981 by American Heart Associationhttps://doi.org/10.1161/01.HYP.3.6_Pt_2.II-177 Originally publishedNovember 1, 1981 PDF download Advertisement

Cardiovascular actions of meptazinol in comparison with pentazocine and morphine

1. In comparative experiments with pentazocine and morphine in anaesthetized cats, the analgesic agent meptazinol (0.1–25.6 mg/kg i.v.) transiently decreased blood pressure, heart rate, left ventricular d p/d t and cardiac effort index. The highest dose was lethal in 2/5 cats. 2. Atropine (1 mg/kg i.v.) attenuated the bradycardia evoked by a single dose of meptazinol (6 mg/kg i.v.) but the hypotensive response was unchanged. 3. Meptazinol (50 mg/kg p.o.) had no significant effects on the blood pressures and heart rates of conscious hypertensive rats.

Antihypertensive Activity of Orally Administered Methyl O-(4-Hydroxy-3-Methoxycinnamoyl) Reserpate (CD-3400) in Conscious Hypertensive Rats

Antihypertensive activity of orally administered methyl O-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400) was examined and compared with such activity of reserpine and its related agents in conscious hypertensive rats. CD-3400, 4–16 mg/kg p.o., produced a marked antihypertensive effect lasting 6 hr and a slight decrease in heart rate in spontaneously hypertensive rats (SHR). Reserpine, 1–4 mg/kg, rescinnamine, 4–16 mg/kg, and syrosingopine, 8–32 mg kg p.o., produced effects similar to those of CD-3400. The order of antihypertensive activities of the agents was as follows: reserpine>CD-3400═rescinnamine>syrosingopine. In renal hypertensive rats and deoxycorticosterone hypertensive rats, CD-3400 and rescinnamine, 4–16 mg/kg, and reserpine, 1–4 mg/kg p.o., also produced an antihypertensive effect and the order of potency was as follows: reserpine>rescinnamine≧CD-3400. Repeated administrations of CD-3400, 2–12 mg/kg/day p.o., for 14 days, to SHR produced the marked constant antihypertensive effects during the administration period. The order of the potency was as follows: reserpine> rescinnamine>CD-3400. CD-3400 possessing a sustained antihypertensive activity may be prescribed in cases when long-term therapy is required for hypertensive patients.

Localization of Catecholaminergic Receptor Sites in the Nucleus Tractus Solitarii involved in the Regulation of Arterial Blood Pressure

This chapter discusses the localization of catecholaminergic receptor sites in the nucleus tractus solitarii (NTS) involved in the regulation of arterial blood pressure. Studies indicate that the NTS of the medulla oblongata—a primary site of termination of afferent carotid sinus baroreceptor fibers—plays an important role. For example, ablation of the area of the NTS produces acute hypertension in conscious rats, and electrical stimulation of the mediocaudal part of the NTS causes hypotension and bradycsudia. This area has been shown by fluorescent histochemistry to be heavily innervated by catecholaminergic terminals; it also contains catecholaminergic cell bodies. Bilateral local application of noradrenaline and α-methylnoradrenaline (MNA) in this area cause hypotension. In addition, prior administration at the same site of the α-adrenergic blocking agent—phentolamine—prevents the central inhibitory action of the two catecholamines and may even reverse the effect on blood pressure. These data suggest that the area of the NTS may be a site of action for central hypotensive drugs that act by adrenergic receptor stimulation in the brain. In experiment, it was found that the minimum effective dose of α-methylnoradrenaline in NTS region causing a hypotensive response after bilateral local application was 80 pmoles. In contrast, an injection of physostigmine in the same region elicited a hypertensive response.

A new antihypertensive compound: 3 hydrazino-6-[(2-hydroxypropyl)methylamino] pyridazine dihydrochloride (ISF 2123)

The new 3-hydrazinopyridazine derivative ISF 2123 was demonstrated to posses a potent and long lasting hypotensive action in different animal species both by intravenous and oral route. Data from acute experiments indicate that after i.v. injection the drug produces a clear cut blood pressure drop at dose levels lower than 0,1 mg/kg in anaesthetized cats and conscious hypertensive rats and lower than 0,03 mg/kg in conscious hypertensive dogs. Repeated treatments with oral doses of 1,2,5 mg/kg in hypertensive rats and with 0,1 mg/kg in hypertensive dogs induce a blood pressure fall with no evidence of a cumulative effect or tolerance. After each administration a heart rate increase was observed. In comparative trials ISF 2123 was 4–14 times more potent and 3–10 times less toxic (acute toxicity) than hydralazine. ISF 2123 does not display any specific activity on central nervous system nor in vitro antagonistic effects against acetylcholine, serotonin, histamine, adrenaline and barium chl o ride. Chronic toxicity trials in rats and dogs indicated that doses far higher than those required for hypotensive activity produce no variation of hystological, haematological or haemat o chemical parameters.

Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats.

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA-NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA-NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.

The cardiovascular effects of intraventricular 5,6-dihydroxytryptamine in conscious hypertensive rats.

1. Conscious experimental hypertensive rats injected intraventricularly with 5,6-dihydroxytryptamine (50 microgram) responded with a rapid and long-lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration. 2. The acute actions of 5,6-dihydroxytryptamine on the cardiovascular system were not modified by pretreatment with bromolysergide (0.5 mg/kg, i.p.), methysergide (2.5 mg/kg, i.p.) or intraventricular phentolamine (200 microgram). 3. The results suggest that central serotonergic neurones play an important role in the regulation of blood pressure. However, the site of action remains to be investigated.

The central hypotensive action of clonidine and BAY 1470 in cats and rats.

1. Intraventricular clonidine and BAY 1470, administered in small doses to conscious renal hypertensive cats, produced a fall in mean blood pressure lasting for a period of 3 h. This fall in blood pressure was accompanied by a marked bradycardia. 2. Pretreatment with intraventricular phentolamine (0.3–6 μmol), piperoxan (0.18–0.74 μmol) or tolazoline (0.35–1 μmol) abolished the hypotensive effects of intraventricular clonidine (74 nmol), whereas pretreatment with haloperidol (2.6 μmol/kg, intraperitoneally), or desmethylimipramine (3.3 μmol/kg, intraperitoneally, or 1.7 μmol, intraventricularly) did not modify the cardiovascular responses to clonidine. 3. Emesis was observed 1 min after intraventricular administration of clonidine (18–112 nmol) or BAY 1470 (0.07–0.14 μmol), which always preceded the cardiovascular actions and was still observed after pretreatment with haloperidol, desmethylimipramine, phentolamine, piperoxan or tolazoline. 4. In conscious hypertensive rats clonidine (0.6 μmol/kg, intraperitoneally) produced a marked fall in blood pressure that was antagonized by centrally acting α-adrenoreceptor blocking agents but not modified by pretreatment with either 6-hydroxydopamine (three doses of 1 μmol, intraventricularly) or 5,6-dihydroxytryptamine (0.1 μmol). 5. It is concluded that the anti-hypertensive responses to clonidine are mediated via stimulation of central α-adrenoreceptors and are independent of central dopaminergic receptors, intact central serotonergic neurons and intact adrenergic uptake mechanisms.

Role of the pressor action of angiotensin II in experimental hypertension.

Experiments with rabbit aortic strips and pithed rats indicated that 1-Sar-8-Ala-angiotensin II (Sar-Arg-Val-Tyr-Val-His-Pro-Ala) is a specific competitive antagonist of the vascular action of angiotensin II. Norepinephrine-induced hypertension was not affected by infusions of 1-Sar-8--Ala-angiotensin II which evoked a dose-related reduction of angiotensin II-induced hypertension in conscious rats. Infusions of 1-Sar-8-Ala-angiotensin II that caused a dose-related reduction of the blood pressure of conscious rats in the acute phase of unilateral renal hypertension were ineffective during the chronic phase of such hypertension. Infusions of 1-Sar-8-Ala-angiotensin II lasting 1 hour did not reduce the blood pressure of normotensive, spontaneously hypertensive, or metacorticoid hypertensive conscious rats. These data indicate that, under certain experimental conditions, the blood pressure of rats during the acute phase of unilateral renal hypertension is maintained hy the endogenous angiotensin II previously demonstrated to he present in the plasma in supernormal concentrations. The blood pressure of normotensive, spontaneously hypertensive, metacorticoid hypertensive, and chronic unilateral renal hypertensive rats previously shown to have normal plasma levels of renin and angiotensin II appeared to be independent of the pres.sor action of endogenous angiotensin II. This is additional direct evidence implicating the pressor action of angiotensin II in the etiology of renal hypertension.