EFFECT OF CAPTOPRIL ON ACETYLCHOLINE-INDUCED RELAXATION IN THE PRESENCE OF NITROGLYCERIN TOLERANCE IN ISOLATED RABBIT AORTA

We investigated the effects of angiotensin converting enzyme inhibitor s on acetylcholine-induced endothelium-dependent vasodilation in the p resence of nitroglycerin tolerance in rings of rabbit thoracic aorta m ounted in tissue baths and precontracted with 10(-6) M norepinephrine. The vasorelaxant effects of acetylcholine were measured before and af ter 1 h treatment. with 5 x 10(-4) M nitroglycerin. The acetylcholine dose-response curve shifted to the right after the induction of nitrog lycerin tolerance. Pretreatment with captopril (a sulfhydryl angiotens in converting enzyme inhibitor), but not with M-1 (a metabolite of del april and a nonsulfhydryl angiotensin converting enzyme inhibitor) res tored acetylcholine-induced relaxation. Pretreatment with N-acetylcyst eine also restored reduced acetylcholine-induced relaxation. These res ults suggest that the sulfhydryl group plays a major role in restorati on of reduced acetylcholine-induce vasodilation in the presence of nit roglycerin tolerance.