The influence of indomethacin on vasodilator responses to bradykinin and nitroglycerin in the cat

Abstract

The effects of indomethacin, a cyclooxygenase inhibitor, on vasodilator responses to bradykinin and nitroglycerin were investigated in the peripheral vascular bed of the anesthetized cat. Intra-arterial injections of bradykinin and nitroglycerin elicited dose-related decreases in mesenteric and hindquarters vascular resistance. Mesenteric vasodilator responses to nitroglycerin in absolute units were unchanged 30 min after administration of indomethacin whereas responses to bradykinin expressed as an absolute mm Hg decrease in perfusion pressure were increased. Indomethacin was also without effect on vasodilator responses to lower doses of nitroglycerin whereas responses to higher doses of nitroglycerin and bradykinin in absolute units were enhanced in the hindquarters vascular bed. Indomethacin increased vascular resistance in the mesenteric and hindquarters vascular beds and decreased systemic vasodepressor responses to the prostaglandin precursor, arachidonic acid. When the increase in (initial value) vascular resistance was taken into account by expressing vasodilator responses on a percent decrease basis, indomethacin only enhanced the vasodilator response to the highest does of bradykinin studies. Result of the present study suggest that products in the cyclooxygenase pathway may serve to maintain the peripheral vascular bed of the cat in a dilated state but that these metabolites do not mediate vasodilator responses to bradykinin. The present data further suggest that products in the cyclooxygenase pathway may play a minor role in modulating the dilator effects of bradykinin in the mesenteric and hindquarters vascular beds of the cat.