EFFECTS OF ANGIOTENSIN-II ON CANINE AND PORCINE CORONARY EPICARDIAL AND RESISTANCE ARTERIES

Coronary resistance arteriolar diameter importantly regulates myocardi al blood flow, and is influenced by circulating neurohumoral agents. A ngiotensin II (A-II) is a circulating polypeptide that is chronically elevated in heart failure and serves as a potent peripheral vasoconstr ictor agent. However, its effects on isolated coronary resistance arte rioles is relatively unknown. We compared the vasomotor effects of A-I I on coronary epicardial and resistance arterioles in vitro from both the canine and porcine heart in order to determine the effects of A-II in different vascular beds and species. Epicardial rings were studied under isometric recording conditions, while resistance arterioles (50 -150 mu m) were studied in vitro using a video imaging system to recor d diameter. A-II, whether applied to passively distended or preconstri cted porcine resistance arterioles, did not cause vasoconstriction whe n applied as a bolus or as cumulative doses. In preconstricted canine resistance arterioles, A-II elicited dose-dependent vasodilation (EC(5 0) = 0.2 nM). In passively distended canine arterioles, high concentra tions of A-II (0.1 mu M) applied as a bolus elicited transient vasocon striction in 28% of the vessels studied. In large epicardial rings, A- II was a weak vasoconstrictor, with greater potency in canine arteries compared to porcine arteries. In canine arteries, vasoconstriction to A-II was augmented after incubation with indomethacin. In contrast to the findings in canine arteries, the A-II vasoconstrictor response in porcine coronary arteries was decreased after incubation with indomet hacin or removal of the endothelium. Thus, A-II elicits the release of a vasodilator prostanoid in epicardial canine coronary arteries and a vasoconstrictor prostanoid in porcine vessels which modulate the vaso motor action of A-II. Receptor binding assays to compare A-II receptor s in resistance arterioles and epicardial arteries showed that porcine arterioles possessed significantly more membrane receptors for A-II t han porcine epicardial vessels, whereas there was no difference betwee n canine epicardial and arteriolar A-II receptor densities. In conclus ion, A-II exerted complex actions on both large epicardial vessels and resistance arterioles, with significant differences between species. A-II was a weak vasoconstrictor in both porcine and canine epicardial vessels. The net vasomotor response was the result of interactions bet ween vasoactive prostanoids and direct smooth muscle vasoconstrictor e ffects on the coronary artery. A-II was a potent vasodilator of canine , but not porcine, resistance arterioles, and in some vessels elicited transient vasoconstriction at high A-II concentrations. Despite the p resence of A-II receptors, in porcine resistance arterioles A-II had n o vasomotor effects in either passively distended or preconstricted ar terioles.