In vivo induction and reversal of nitroglycerin tolerance in human coronary arteries.

Abstract The mechanism by which tolerance to the clinical effects of organic nitrates develops has not been elucidated. This study was done to determine whether an intravenous infusion of nitroglycerin induces tolerance in the coronary vascular bed and whether such tolerance is reversed by the sulfhydryl-group donor W-acetylcysteine. We studied 19 subjects — 17 with coronary artery disease and 2 without it — who had a mean age (±SD) of 54±9 years. Coronary sinus blood flow, which approximates blood flow to the left ventricle, was measured before and during intracoronary injections of nitroglycerin (10, 25, 50, and 100 μg). The patients then received a 24-hour intravenous infusion of saline (n = 7) or of nitroglycerin, 45±13 μg per minute (n = 12), after which the responses of coronary sinus flow to the same doses of intracoronary nitroglycerin used earlier were measured. In the seven patients given saline, the four doses of intracoronary nitroglycerin caused similar percentage increases in coronary sinus ...