ENDOTHELIUM-DEPENDENT RELAXATION BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN CANINE FEMORAL ARTERIES

The effects of angiotensin-converting enzyme (ACE) inhibitors on vascu lar reactivity were investigated using isolated canine femoral arterie s with and without endothelium. boxy-3-phenylpropyl-L-alanyl-N-(indan- 2-yl)glycine (M-1; an active metabolite of delapril, a nonsulfhydryl A CE inhibitor) and captopril (a sulfhydryl ACE inhibitor, 10(-8) to 10( -5) M) relaxed in a dose-dependent manner canine femoral arterial ring s precontracted with prostaglandin F-2 alpha in the presence of endoth elium only. The endothelium-dependent relaxations by M-1 and captopril were completely blocked by methylene blue, an inhibitor of soluble gu anylate cyclase; N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of n itric oxide synthesis; and oxyhemoglobin, an inactivator of nitric oxi de; they were partially blocked by aspirin, an inhibitor of cyclooxyge nase and were enhanced by superoxide dismutase, a radical scavenger. T he inhibitory effect of L-NMMA on the relaxations by M-1 and captopril were reversed by a high dose of L-arginine. Moreover, a bradykinin an tagonist partially inhibited these relaxations. These results suggest that endothelium-dependent relaxations by M-1 and captopril in canine femoral arteries are mediated through the release of both prostanoids and endothelium-derived nitric oxide via endogenous bradykinin.