Alpha-adrenoceptor subtypes and diltiazem actions in isolated human coronary arteries.

Abstract

Isolated human, monkey, and dog coronary arteries treated with propranolol responded to norepinephrine with concentration-related contractions; the magnitude was in the order of human greater than monkey greater than dog arteries. Phenylephrine also contracted these arteries, whereas clonidine produced contractions only in the primate arteries. Contractile responses of human coronary arteries to norepinephrine were not influenced by removal of endothelium. Norepinephrine-induced contractions of human and monkey coronary arteries were attenuated by prazosin and yohimbine in a dose-dependent manner; however, the amine-induced contractions of dog coronary arteries were attenuated only by prazosin. Diltiazem, a Ca2+ antagonist, relaxed human and dog coronary arteries contracted with norepinephrine to a similar extent, but produced a greater relaxation in the human arteries when partially contracted with prostaglandin F2 alpha. These findings suggest that alpha 1- and alpha 2-adrenoceptors are involved in the amine-induced contraction in human and monkey coronary arteries, whereas only alpha 1-receptors are involved in dog artery contraction. Human coronary artery contractions induced by norepinephrine do not appear to be more susceptible to Ca2+ antagonists than the dog artery contractions, which does not provide evidence supporting the hypothesis that Ca2+ antagonists interfere with contractions mediated by alpha 2-receptors to a greater extent than those mediated by alpha 1-receptors in large human coronary arteries.