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Investigation of a combined arteriolar dilator and beta‐adrenoceptor antagonist (SK & F 92657) in the peripheral vessels of man.
Author(s) -
Collier JG,
Pitcher DW
Publication year - 1980
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1980.tb00512.x
Subject(s) - dilator , antagonist , peripheral , adrenergic beta antagonists , adrenergic receptor , medicine , endocrinology , pharmacology , chemistry , propranolol , receptor
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.