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CLINICAL STUDY: CORONARY ARTERY DISEASE

N-acetylcysteine improves coronary and peripheral vascular function

^* Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

Manuscript received March 21, 2000; revised manuscript received August 15, 2000, accepted September 26, 2000.

Reprint requests and correspondence: Dr. Arshed A. Quyyumi, National Institutes of Health, Cardiology Branch, NHLBI, Bldg.10, Rm. 7B15, 10 Center Drive, MSC 1650, Bethesda, Maryland 20892-1650
quyyumia{at}nih.gov

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 dysfunction and reduced NO activity.

METHODS

In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC.

RESULTS

Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 ± 11% higher (p < 0.02), and epicardial diameter changed from –1.2 ± 2% constriction to 4.7 ± 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated 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 and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05).

CONCLUSIONS

Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

Abbreviations and Acronyms   ACH = acetylcholine   CV = coefficient of variation   NAC = N-acetylcysteine   NO = nitric oxide   NTG = nitroglycerin   SNP = sodium nitroprusside

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