ABSTRACT
Amlodipine, a dihydropyridine calcium antagonist has been examined on the rhythmic activity of isolated human coronary arteries. Amlodipine inhibited both the spontaneous rhythmic activity and the rhythmic activity evoked by prostaglandin F2 alpha and endothelin in isolated human coronary arteries. It also inhibited the contraction evoked by potassium depolarization. The action of amlodipine was characterized by slow onset and voltage dependency.
Subject(s)
Coronary Vessels/drug effects , Dinoprost/pharmacology , Peptides/pharmacology , Amlodipine , Calcium Channel Blockers , Coronary Vessels/physiology , Electrophysiology , Endothelins , Endothelium, Vascular , Humans , In Vitro Techniques , Nifedipine/pharmacology , Papillary Muscles/drug effects , Peptides/antagonists & inhibitors , Potassium/pharmacology , Vasoconstriction/drug effects , VasodilationABSTRACT
Rat isolated aorta was more sensitive to the contractile effect of endothelin-1 (ET-1) when the endothelium was removed. ET-1 was more potent on mesenteric resistance arteries than on aorta. A threshold concentration of ET-1 (100 pM) enhanced the contractile responses of aortic rings to Bay K 8644 and clonidine, especially in the absence of endothelium. Potentiation of clonidine-evoked contraction was accompanied by an enhancement of 45Ca influx and was abolished by nifedipine. These actions of ET-1 (100 pM) could not be attributed to a decrease in membrane potential or in cAMP levels. ET-1 (100 pM) decreased cGMP in intact aortic rings, which could contribute to its actions in the presence of endothelium. Removal of endothelium reduced cGMP levels and these were not further decreased by ET-1. Since ET-1 exerted a pronounced potentiating effect in the absence of endothelium, it is likely that ET-1 modulates calcium channels by an additional mechanism, unrelated to cyclic nucleotides.
