N-acetylcysteine improves coronary and peripheral vascular function

OBJECTIVES We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. BACKGROUND Coronary atherosclerosis is associated with endothelial dysfunct ion and reduced NO activity. METHODS In 16 patients undergoing cardiac catheterization, seven with and n ine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nit roglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoron ary NAG. In 14 patients femoral vascular responses to AGH, NTG and SNP were measured before and after NAG. RESULTS Intraarterial NAC did not change resting coronary or peripheral vas cular tone. N-acetylcysteine potentiated AGH-mediated coronary vasodilation ; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diam eter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly pote ntiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations an d did not alter SNP responses in the femoral circulation. In contrast, coro nary vasodilation with SNP was significantly greater after NAC (p < 0.05). CONCLUSIONS Thiol supplementation with NAC improves human coronary and peri pheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary c irculation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeut ic benefit in treating acute and chronic manifestations of atherosclerosis. (J Am Cell Cardiol 2001;37:117-23) (C) 2001 by the American College of Car diology.