Abstract
We investigated the effects of angiotensin converting enzyme inhibitors on acetylcholine-induced endothelium-dependent vasodilation in the presence of nitroglycerin tolerance in rings of rabbit thoracic aorta mounted in tissue baths and precontracted with 10(-6) M norepinephrine. The vasorelaxant effects of acetylcholine were measured before and after 1 h treatment with 5 x 10(-4) M nitroglycerin. The acetylcholine dose-response curve shifted to the right after the induction of nitroglycerin tolerance. Pretreatment with captopril (a sulfhydryl angiotensin converting enzyme inhibitor), but not with M-1 (a metabolite of delapril and a nonsulfhydryl angiotensin converting enzyme inhibitor) restored acetylcholine-induced relaxation. Pretreatment with N-acetylcysteine also restored reduced acetylcholine-induced relaxation. These results suggest that the sulfhydryl group plays a major role in restoration of reduced acetylcholine-induced vasodilation in the presence of nitroglycerin tolerance.
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