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Biomedical subjects

H F Oates

Publications and source records attributed to H F Oates.

At least 19 recordsLinked to original sources
PubMed1981

Studies in the rat on bucindolol, a new antihypertensive agent with beta-adrenoceptor blocking properties.

The properties of a new antihypertensive agent, bucindolol, were studied in the anaesthetized rat. When administered intravenously in the dose range 0.03 to 1.0 mg/kg, bucindolol evoked dose-related decreases in mean arterial blood pressure wtih relatively little change in heart rate. Bucindolol retained nearly 50% of its hypotensive activity after ganglionic blockage with pentolinium. When administered intravenously in a dose of 0.25 mg/kg, bucindolol caused approximately 1000-fold and 100-fold shifts to the right in the dose-response curves for isoprenaline-induced chronotropic activity and hypotensive activity, respectively. The same dose of bucindolol caused a decrease in pressor responsivity to angiotensin II, no significant change in that to noradrenaline, and an increase in that to adrenaline. Bucindolol was an effective hypotensive agent, which under the conditions of test, had relatively little effect on basal heart rate, exhibited no significant alpha-adrenoceptor blocking activity in the dose range tested, had potent beta-adrenoceptor blocking properties, and exhibited an apparent direct relaxant effect on vascular smooth muscle.

Adrenergic beta-Antagonists↗
PubMed1979

Relationship between the hypotensive and alpha-adrenoceptor blocking actions of prazosin.

The relationship between the hypotensive and alpha-adrenoceptor blocking actions of prazosin was investigated in anaesthetized rats. Pressor responses to norepinephrine and angiotensin II were determined before and after intravenous administration of prazosin, 0.0005 to 0.7 mg/kg. The prazosin-induced reduction in mean arterial pressure was recorded immediately before measurement of 87 such pairs of pressor reponses. The percentage antagonism of norepinephrine-induced pressor responsivity, corrected where necessary for non-specific changes in pressor sensitivity, was used as an index of alpha-adrenoceptor blockade. Linear regression analysis of the data revealed that there was a highly significant correlation between the degree of alpha-adrenoceptor blockade afforded by prazosin and the hypotensive response to the drug. The findings extend those of previous studies in which alpha-blocking properties of prazosin were demonstrated using doses of the drug 10(2) to 10(4)-fold greater than those producing significant hypotensive effects. The present results show that prazosin exhibits alpha-adrenoceptor blocking properties at much lower doses, such that a close relationship exists between its alpha-blocking activity and its hypotensive effects.

Adrenergic alpha-Antagonists↗
PubMed1978

The beta-adrenoceptor controlling renin release.

The beta-adrenoceptor antagonists, atenolol, metoprolol and propranolol, administered intravenously to anaesthetized rats in doses producing equal beta1-adrenoceptor blocking effects, caused comparable suppression of plasma renin activity (PRA) despite the fact that, at these doses, atenolol and metoprolol exhibited no beta2-adrenoceptor blocking properties. Practolol, an agent specific for beta1-adrenoceptors but possessing intrinsic sympathomimetic activity, caused less marked suppression of PRA. When doses of atenolol, metoprolol, propranolol and butoxamine were selected to achieve equal beta2-blocking effects, PRA was again significantly suppressed by atenolol and metoprolol but not by propranolol or butoxamine. These results do not support the concept that adrenergic release of renin is mediated by beta2-adrenoceptors, but are compatible with the involvement of a beta1-adrenoceptor-mediated mechanism.

Angiotensin II↗
PubMed1978

Withdrawal of clonidine: effects of varying dosage or duration of treatment on subsequent blood pressure and heart rate responses.

The influence of the dosage or duration of treatment on the incidence and severity of clonidine withdrawal responses was examined in normotensive rats. Clonidine (0.01 or 0.1 mg/kg i.m.) was administered either in single doses, or twice daily for 3 days or 3 weeks. Rats were then anesthetized and arterial catheters were inserted. Significant overshoots in blood pressure and heart rate, reaching peak values 16 to 26 hr after the last injection, occurred in all clonidine-treated rats, but in no control rats. The overshoots after single injections of clonidine were as great as those after suspension of sustained treatment. Moreover, withdrawal responses were as great after the low dose as they were after the 10-fold greater dose. Only plasma renin activity showed a significantly greater elevation during withdrawal of the high dose of clonidine. Since ganglionic blockade reduced blood pressures and heart rates to the same levels in rats with clonidine withdrawal hypertension as in control rats, the withdrawal overshoots appear to be nervously mediated. Neither the dosage nor the duration of treatment could be shown to determine the magnitude of the response to withdrawal of clonidine.

Animals↗
PubMed1978

Comparative haemodynamic effects of clonidine and guanfacine.

Dose-response relationships were established for the acute effects on arterial pressure and heart rate of the antihypertensive agents, clonidine and guanfacine, administered intravenously or intramuscularly to anaesthetized rats. The intramuscular route appeared to be preferable to the intravenous, for the direct pressor potency of each drug was thereby greatly reduced in relation to the hypotensive efficacy. The potency of clonidine was 10-20 times that of guanfacine, but the same maximal fall in blood pressure was obtained with either agent administered by either route. Both agents caused a marked, dose-related suppression of plasma renin activity. When either clonidine or guanfacine was administered twice daily for 3 weeks and then discontinued, a phase of blood pressure overshoot with tachycardia commenced within 24 hr of the last injection. These withdrawal effects were more evident in guanfacine-treated rats than in clonidine-treated rats.

Animals↗
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↗