Investigation of a combined arteriolar dilator and beta-adrenoceptor antagonist (SK & F 92657) in the peripheral vessels of man.
1 SK & F 92657 is a new compound which in animals has both precapillary vasodilator and beta-adrenoceptor blocking activity. The effects of the drug on forearm blood flow and dorsal hand vein distensibility have been studied in healthy volunteers. 2 Forearm blood flow was measured by venous occlusion plethysmography. The drug was infused directly into a brachial artery. The effects of SK & F 92657 on resting flow and on the dose-response relationship for intra-arterial isoprenaline were studied. 3 Venous distensibility was measured in the large veins on the back of the hand. The drug was infused directly into a selected vein and its effects on resting tone and on the responses to noradrenaline and to isoprenaline were investigated. 4 Intra-arterial infusion of SK & F 92657 over 2 min caused a dose-dependent increase in forearm blood flow which developed gradually to reach a maximum after approximately 40 min. Infusion into dorsal hand veins at 100 ng/min and 500 ng/min had no dilator effect in veins preconstricted with noradrenaline. At higher doses SK & F 92657 potentiated the constrictor effect of noradrenaline. 5 In both veins and arteries SK & F 92657 attenuated the dilator effects of isoprenaline. The drug had no effect on the venodilator effects of bradykinin, histamine or sodium nitroprusside. 6 The pattern of response of these vessels to locally infused SK & F 92657 is exactly that expected of a drug combining the properties of hydralazine-like vasodilatation and beta-adrenoceptor blockade. Furthermore, in the arterioles, both properties were manifest at the same dose.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001808:Blood Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D005542:Forearm / Q000098:blood supply; D006225:Hand / Q000098:blood supply; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D006834:Hydrazines; D011724:Pyridazines; D014665:Vasodilator Agents; C024293:prizidilol