Contractile actions of racemic and d-propranolol on isolated canine mesenteric and coronary arteries.
This investigation was undertaken to determine whether propranolol exerts a direct vasoconstriction action which contributes to the increased systemic and regional vascular resistance observed after its acute administration. Helically cut strips of canine mesenteric and coronary arteries were exposed to cumulative concentrations of racemic propranolol, d-propranolol, metoprolol and sotalol. Racemic and d-propranolol were equipotent in eliciting concentration-related increments in tension in the mesenteric (3 x 10(-6)-3 x 10(-5) M) and coronary (3 x 10(-7)-3 x 10(-5) M) arterial strips. Metoprolol and sotalol did not cause contractions in concentrations up to 10(-4) M. Phenoxybenzamine, 10-(-6) M, did not alter the contractile responses elicited by racemic and d-propranolol. Upon exposure of mesenteric strips to calcium-free media or 10(-6) M verapamil, the contractile responses to propranolol (3 x 10(-5) M) and KCl (30 mM) were markedly reduced (not significantly different), whereas norepinephrine (10(-6) M)-induced responses were inhibited to a significantly lesser degree. In coronary arteries exposed to calcium-free media or 10(-6) M verapamil, the responses to propranolol, KCl and methoxamine (10(-5) M) were all extensively decreased (not significantly different). These results indicate that propranolol exerts a direct contractile effect on canine mesenteric and coronary arteries, which is unrelated to its beta adrenergic blocking activity and is not mediated through action on alpha adrenergic receptors. The propranolol-induced contraction appears to be associated predominantly with an influx of calcium ion.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D013237:Stereoisomerism; D014700:Verapamil / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D010643:Phenoxybenzamine; D011433:Propranolol; D014700:Verapamil; D002118:Calcium