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Biomedical subjects

G S Stokes

Publications and source records attributed to G S Stokes.

At least 91 records · Page 5Linked to original sources
PubMed1977

Alpha blocking action of the antihypertensive agent, prazosin.

The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1977

Mechanism of the hypotensive action of prazosin.

The mechanism of action of prazosin was studied in anesthetized rats by comparison with the peripherally-acting anti-hypertensive agents, indoramin, hydralazine and diazoxide. Hydralazine and diazoxide retained full hypotensive potency after ganglionic blockade with pentolinium or alpha adrenoceptor blockade with phentolamine. Hydralzaine and diazoxide also attenuated angiotensin II pressor responses. In contrast, the hypotensive activity of prazosin was completely abolished, and that of indoramin was almost abolished by either pentolinium or phentolamine pre-treatment. Neither prazosin nor indoramin caused impairment of angiotensin II responsivity, but each was shown to possess alpha adrenoceptor blocking properties. Both agents antagonized the pressor action of norepinephrine and reversed responses to epinephrine. Thus, while hydralazine and diazoxide act directly upon the vasculature by mechanisms independent of sympathetic vasomotor tone, prazosin, like indoramin, acts as an alpha adrenoceptor blocking agent.

Angiotensin II↗
PubMed1976

Surgical intervention in severe and complicated renal hypertension: Report of the Sydney Renal Hypertension Group (1969-75).

1. A prospective study was undertaken in seventy-eight patients with renal hypertension (fifty-eight with renovascular disease and twenty with renal parenchymal disease), after their presentation to an advisory group as possible candidates for surgical management. 2. Vascular repair and/or nephrectomy were performed in forty-four patients, and the remainder were treated with anti-hypertensive drugs. The control of blood pressure was then assessed over periods of 6-70 months. 3. Of the patients treated surgically, fifteen (34%) were normotensive without medication and fifteen had improved blood pressure control; the morbidity rate was the same as in the medically treated group, but mortality was lower and blood pressure control was better, particularly among patients under 40 years of age. 4. Surgery undertaken primarily to conserve renal function was beneficial in four of nine patients with bilateral renal artery stenosis and severe, progressive uraemia. 5. The blood pressure response to surgical correction of unilateral renal lesions was predicted correctly by the preoperative renal vein renin ratio in fifteen of eighteen cases.

Adult↗
PubMed1976

Diazoxide-induced renin release in diagnosis of remediable renovascular hypertension.

In hypertensive patients with unilateral renal artery stenosis, intravenous diazoide increased renal vein renin activity more on the involved side than on the contralateral side, whereas, in a group with predominantly unilateral renal parenchymal disease, the increase in renal vein was similar for both kidneys. In patients with bilateral renal artery stenosis, the use of diazoxide was helpful in lateralizing the dominant ischaemic lesion. Diazoide administration appears to be a safe, rapid and convenient method of increasing the sensitivity of the renal vein renin test used in predicting the outcome of surgical treatment of renovascular hypertension. Bilateral renal vein renin determination of established value in the diagnosis of functional renal ischaemia. 1-4 However, in the use of this procedure to predict the efficacy of corrective surgery, false positive and false negative results still occur. Thus, various manoeuvres which stimulate renin release have been employed to improve the sensitivity of the test. 5-7 We report a new application the practical approach to of this procedure in the diagnosis of renal hypertension, which both basal and stimulated levels of renal venous renin activitity can be measured during a brief period of bilateral renal vein catherization.

Adolescent↗
PubMed1976

The role of renin in the antihypertensive action of beta-adrenoreceptor blocking agents.

Since the original reports suggesting that the antihypertensive action of beta-adrenoreceptor blocking drugs is related to their inhibitory action on renin release, much evidence has been put forward both to refute and support this hypothesis. Our studies of the acute and chronic effects of treatment with propranolol in hypertensive patients showed that the antihypertensive action of the drug was of later onset than the initial cardio-depressant and renin-suppressive effects and had little relationship to the pre-treatment levels of treatment-induced changes in plasma renin activity (PRA). When pindolol was substituted for propranolol in these studies PRA rose, but blood pressure control was undisturbed. Again, in animal experiments, although a range of different beta-adrenoreceptor blocking agents induced decreases in both blood pressure and PRA, the hypotensive effects of pindolol was associated with a rise in PRA. Further, PRA proved to be a poor guide to therapeutic effectiveness in the treatment of an unselected population of hypertensive patients with propranolol. It is concluded that the antihypertensive action of beta-adrenoreceptor blocking agents, as a class, is not dependent upon suppression of PRA.

Adrenergic beta-Antagonists↗
PubMed1976

Haemodynamic effects of prazosin.

Parzosin, 0.001 to 10 mg/kg, was administered intravenously to anesthetized normal rats. In the dose range 0.001 to 0.01 mg/kg, the drug induced highly significant, dose-related falls in blood pressure, pulse pressure and heart rate. With doses above 0.01 mg/kg, there was a plateau in hypotensive efficacy and a diminution in negative chronotropic activity. Both actions of prazosin (0.01 mg/kg) were unaffected by vagal blockade with atropine, while hypotensive potency was unimpaired after beta-adrenoreceptor blockade. The vasodilator, diazoxide, lowered blood pressure, widened pulse pressure and caused tachycardia in rats pre-treated with pentolinium. In contrast, all effects of prazosin were abolished by ganglion blockade. These findings, together with the absence of compensatory tachycardia or gross renin hypersecretion during prazosin-induced hypotension, are compatible with an antisympathotonic mode of action for the drug. However, consistent with its effects on cyclic nucleotide distribution, prazosin appears to enhance isoprenaline-induced beta-receptor stimulation.

Animals↗
PubMed1976

Suppression of renin release by timolol.

The beta-adrenergic blocking agent, timolol, administered to resting rabbits as an i.v. bolus (0.125 mg/kg) sustained by a 2-hr infusion at 0.0625 mg/kg/hr, caused significant depression of plasma renin activity (PRA) to 49% of the control level. Significant correlations emerged between the fall in mean blood pressure and changes in both heart rate and PRA. Timolol also antagonized isoprenaline-induced renin release. In anaesthetized normal rats, timolol (0.2 mg/kg i.p.) suppressed mean plasma renin concentration (PRC) to 16% of the pre-treatment value. Furthermore, the mean PRC of normal rats, bled immediately after decapitation, to avoid stimulating renin secretion, was reduced by 55% one hr after i.p. injection of timolol. The potency of timolol in this respect was 8 times that of dl-propranolol. Thus, in rabbits and rats, timolol effectively depresses both basal and stimulated plasma renin levels.

Adrenergic beta-Antagonists↗
PubMed1975

Treatment of hypertension with an antihypertensive agent possessing vasodilator activity.

Administration of the vasodilator agent, prazosin, in dosages from 3-0 to 7-5 mg per day, significantly reduced diastolic and systolic blood pressure in a group of 14 patients with mild or moderate hypertension. Nine of these patients had a lowering of diastolic blood pressure which was at least 10 mm Hg greater than that caused by placebo. Side effects, chiefly dizziness or lassitude, occurred in over half the patients, but were mild and of short duration and did not necessitate suspension of treatment. The antihypertensive effect of prazosin was similar to that produced by methyldopa or propranolol given in comparable doses. If prazosin and propranolol were given concurrently, blood pressure fell to a level which was significantly lower than that associated with the use of either of these agents alone.

Antihypertensive Agents↗
PubMed1975

Angiotensin blockade in studies of the feedback control of renin release in rats and rabbits.

1. In rabbits actively immunized against angiotensin II (AII), the appearance of anti-AII antibodies was associated with a rise in plasma renin activity (PRA), which did not occur in mock-immunized controls. 2. In conscious rabbits, infusion of the angiotensin inhibitor, Sar1-Ala8-angiotensin II (P-113), at rates of 0.055, 0.22 or 1.1 nmol min-1 kg-1 into the renal artery, caused dose-related increases in arterial PRA and renal arteriovenous PRA difference. Renal blood flow fell with the high dose, but not with the low or medium doses. A fall in arterial pressure, asynchronous with peak renin secretion, accompanied the medium- and high-dose infusions. 3. Intravenous infusion of inhibitor P-113, 5.5 nmol min-1 kg-1, into anaesthetized rats produced highly significant increases in PRA and plasma renin concentration without reduction in arterial pressure. There were no changes in PRA or plasma renin concentration in saline-infused control rats. 4. These findings suggest that AII blockade interrupts a negative feedback loop controlling renin secretion.

Angiotensin II↗
PubMed1975

beta-Adrenergic receptors and renin release: studies with beta-adrenoreceptor-blocking agents in the conscious rabbit.

1. Plasma renin activity (PRA) and mean blood pressure were studied in conscious rabbits infused with beta-adrenoreceptor antagonists. 2. Oxprenolol and DL-propranolol each significantly reduced PRA and blood pressure, but prindolol, which had a strong blood pressure-lowering effect, increased PRA. 3. When prindolol was given to animals in which PRA and blood pressure had been reduced by DL-propranolol, PRA returned to control values but blood pressure remained low. Thus the increase in PRA caused by prindolol is not mediated by hypotension. These findings, together with the observation that compound H35/25 reduced PRA without altering blood pressure, suggest that the effects of the beta-adrenoreceptor-blocking drugs on blood pressure are unrelated to their effects on renin release. 4. Studies with D-propranolol and with blocking agents with either beta-1 or beta-2 specificity indicated that the effects of beta-adrenoreceptor blockade on renin are directly dependent upon their action on beta-adrenergic receptors, probably of the beta-2 type.

Adrenergic beta-Antagonists↗
PubMed1975

Effects of sodium depletion on plasma renin activity and on the urinary excretion of cyclic AMP and aldosterone in hypoparathyroid patients.

The effect of sodium depletion on plasma renin activity (PRA), urinary cyclic AMP and urinary aldosterone excretion was studied in hypoparathyroid patients whose basal urinary cylic AMP excretion (urinary cAMP) was less than 50% of that observed in normal subjects. During 7 days of sodium depletion, PRA, urinary aldosterone and urinary cAMP each rose significantly. Administration of the beta-blocker propranolol, 160 mg/day, during 5 further days of sodium depletion produced a fall in PRA and urinary cAMP, but no change in urinary aldosterone excretion. The dissociation in these effects suggests that the increase in aldosterone secretion during sodium depletion may be mediated by pathways other than the renin-angiotensin and adenyl cyclase systems. There was a high degree of correlation between PRA and urinary cAMP (P less than 0.001) during the period of sodium depletion, but not significant relationship between these parameters was found during control and propranolol phases, or in control studies in normal subjects. These findings suggest that beta-adrenergic receptors have a role in mediating the effects of sodium depletion upon renin secretion and adenyl cyclase activity.

Adult↗
PubMed1974

Role of extrapulmonary conversion in mediating the systemic pressor activity of angiotensin I.

The effect of antibodies against angiotensin II (AII) on systemic pressor responses to intravenously injected AII and angiotensin I (AI) was studied in a group of bioassay rats. AII antibody was only 29% as effective in neutralizing AI given intravenously as it was in neutralizing AII injected by the same route. Control plasma caused no change in the relative potencies of AI and AII. In a further series of experiments, AII antibody was significantly less effective in blocking intra-arterial AI than in blocking intravenous AI. The potency of intra-arterial AI, initially less than that of intravenous AI, became nearly twice that of intravenous AI after antibody administration, a result which could not occur if AI were inactive before lung transit. Thus, AI can elicit systemic pressor activity independently of pulmonary conversion to AII. However, since the intra-arterial AI responses were abolished by an inhibitor of angiotensin-converting enzyme, the activity would appear to be mediated by peripheral conversion to AII rather than by an intrinsic action of the decapeptide. Both series of experiments suggest that the efficacy of AII antibody in abolishing the systemic pressor activity of AI is highly dependent on the site of conversion of the AI to AII. The occurrence of localized intramural conversion of AI to AII near arteriolar receptors in vivo may so minimize exposure of the liberated AII to circulating antibody as to render AII immunization an inefficient means of blocking endogenous pressor activity of the renin-angiotensin system.

Angiotensin II↗
PubMed1974

Prazosin: preliminary report and comparative studies with other antihypertensive agents.

In a group of 14 hypertensive patients a 10-week course of treatment with prazosin 3-7.5 mg/day produced a significant reduction in mean blood pressure without serious side effects. The fall in diastolic pressure exceeded the response to a placebo by 10 mm Hg or more in 9 patients. The average decrease in diastolic pressure was similar to that produced by methyldopa 750 mg/day or propranolol 120-160 mg/day but the fall in systolic pressure was comparatively smaller, consistent with reported experimental work showing that the drug causes vasodilatation. The hypotensive effect of prazosin 1.5-3 mg/day combined with propranolol was significantly greater than that of propranolol alone and resulted in good control of blood pressure.

Adult↗