ROLE OF LIPOXYGENASE PRODUCTS IN THE EFFECTS OF ANGIOTENSIN-II IN THEISOLATED AORTA AND PERFUSED HEART OF THE RAT

THE objective of this study was to determine whether arachidonate meta bolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) sign ificantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug), In the heart, the no nselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 m u M) markedly suppressed the angiotensin II-induced decreases in coron ary flow, NDGA (10 mu M) inhibited both angiotensin II- and methoxamin e(reference drug) induced contractions in aortic rings with (in the pr esence of L-NAME) and without endothelium. In the heart, the leukotrie ne synthesis inhibitor MK-886 (0.3 mu M) significantly reduced the max imal effects to angiotensin II, but the leukotriene antagonist FPL 557 12 (0.1 and 0.3 mu M) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases hn coronary now ar e in part mediated by lipoxygenase products, which might be derived fr om the 5-lipoxygenase pathway, but are probably not leukotrienes. Furt hermore, endothelium independent lipoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta .