Biomedical subjects

D J Sumner

Publications and source records attributed to D J Sumner.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Effect of age on the responsiveness of vascular alpha-adrenoceptors in man.

Aging has been reported to alter the responsiveness of beta-receptors, but there have been few comparable studies of alpha-receptors. This study compares in six young and six healthy elderly subjects the haemodynamic effects of the alpha 1 -antagonist prazosin and the pressor responses to the alpha 1-agonist phenylephrine. Prazosin orally lowered erect (but not supine) blood pressure in both groups by a similar amount between 2 and 6 h after dosing. Maximal falls in systolic pressure were 19.5 +/- 15.7 and 29.3 +/- 11.4 mm Hg (mean +/- SD) in young and old, respectively. There was a significant difference in the associated heart rate response: in the young group mean heart rate increased to 103 beats/min, but there was no corresponding increase in the elderly group, which has a mean heart rate of 80 beats/min. Following the intravenous infusion of increasing doses of phenylephrine, log dose-response curves were deprived, and the dose required to raise mean arterial pressure by 20 mm Hg (PD20) was compared. The mean PD20 was significantly different in the two groups: 2.5 +/- 1.6 in the young, compared to 4.6 +/- 2.3 micrograms/kg/min in the elderly. However, no significant difference was apparent when pressor responsiveness was determined following the administration of prazosin. Thus, while there is no evidence of an age-related increase in the sensitivity of alpha-adrenoceptor-mediated vasoconstriction, the data are not inconsistent with an age-related reduction in responsiveness to alpha-adrenoceptor activation.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Acute effects of phenoxybenzamine on alpha-adrenoceptor responses in vivo and in vitro: relation of in vivo pressor responses to the number of specific adrenoceptor binding sites.

Pressor responses to intravenous phenylephrine, an adrenoceptor agonist, and to the alpha 2-adrenoceptor-selective agonist guanabenz were examined in conscious rabbits 30 min after treatment with a range of doses of phenoxybenzamine (10(-5) to 5 mg/kg). The maximum number of specific prazosin- and clonidine-binding sites in the spleen of rabbits sacrificed 30 min after receiving phenoxybenzamine were measured using radioligand binding techniques. Treatment with phenoxybenzamine resulted in a dose-dependent reduction in the maximum pressor response to both phenylephrine and guanabenz, although phenoxybenzamine was a more potent antagonist at postsynaptic alpha 1- than at postsynaptic alpha 2-adrenoceptors. Phenoxybenzamine treatment also caused a dose-dependent reduction in specific [3H]prazosin and [3H]clonidine binding. The maximum in vivo pressor response to guanabenz was observed only when all specific clonidine-binding sites were present. There was a close correlation between in vitro receptor number and in vivo pressor responses for alpha 2-adrenoceptor stimulation but not for alpha 1-adrenoceptor-mediated responses. The maximum pressor response to phenylephrine could be obtained in rabbits in which the number of specific prazosin-binding sites was reduced by 60%. These experiments provide an approach to relating in vitro receptor number to in vivo responses.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Clinical evaluation of the vasodilator MDL-899 in patients with essential hypertension.

In this study of 10 patients with essential hypertension inadequately controlled by standard beta-blocker-diuretic combination therapy, the addition of 5 mg of MDL-899, a peripheral arteriolar vasodilator, resulted in significant reductions in blood pressure, both supine and standing, which was maximal 4-8 h after dosing, with no additional orthostatic component. There were associated small rises in heart rate but no evidence of significant activation of the sympathetic or renin-angiotensin systems. Six patients continued for 4 weeks receiving MDL-899 twice daily with significant improvement in their blood pressure control--from a mean of 182/95 to 146/77 mm Hg (supine) and from 161/93 to 138/79 mm Hg (erect). These six patients experienced no significant side effects, but four patients were unable to proceed with the study as a result of adverse effects, particularly headache, following the first few doses. It seems likely that these side effects are dose related. In a combined drug regimen, MDL-899 is an effective vasodilator drug that significantly improved the blood pressure control of patients with essential hypertension.

Aged↗

PubMedDate not supplied

Effect of calcium channel blockers on adrenergic and nonadrenergic vascular responses in man.

There is evidence that responses mediated via alpha adrenoceptors are dependent on calcium fluxes and it has been suggested that the alpha 2 adrenoceptor is particularly associated with the increased entry of extracellular calcium ions, which is preferentially antagonised by calcium channel blocking drugs. This study investigates in normotensive men the effects of calcium antagonism with verapamil and the dihydropyridine nisoldipine on the pressor responses to adrenergic and nonadrenergic vasoconstriction. Phenylephrine and alphamethylnoradrenaline were intravenously infused to assess respectively alpha 1 and alpha 2 adrenoceptor-mediated peripheral vascular responsiveness and angiotensin II was used to assess nonadrenergic responsiveness. After 4 days oral treatment, both verapamil and nisoldipine significantly attenuated the responses to angiotensin II with three- to fivefold rightward shifts of the mean pressor dose-response curves. Rightward shifts of comparable magnitude were obtained for phenylephrine but with alphamethylnoradrenaline, although the overall trend was similar, only nisoldipine caused a significant twofold rightward shift. These data demontrate, in humans, that peripheral vascular adrenergic responses mediated via both alpha 1 and alpha 2 adrenoceptors are affected by calcium channel blocking drugs. There was no evidence that this effect was specifically linked to the alpha 2 adrenoceptor.

Adult↗