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CLINICAL STUDIES

Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability

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

Manuscript received August 7, 1998; revised manuscript received March 8, 1999, accepted April 21, 1999.

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

OBJECTIVES

We investigated whether glutathione (GSH), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion and NO activity in atherosclerosis.

BACKGROUND

Endothelial dysfunction and reduced NO activity are associated with atherosclerosis and its clinical manifestations such as unstable angina.

METHODS

In the femoral circulation of 17 patients with atherosclerosis or its risk factors, endothelium-dependent vasodilation with acetylcholine (ACH), and endothelium-independent vasodilation with nitroglycerin and sodium nitroprusside were studied before and after GSH. In 10 patients, femoral vein plasma cyclic guanylate monophosphate (cGMP) levels were measured during an infusion of ACH before and after GSH. Femoral artery flow velocity was measured using a Doppler flow wire and the resistance index (FVRI) calculated as mean arterial pressure ÷ flow velocity.

RESULTS

Glutathione strongly potentiated ACH-mediated vasodilation; at the two doses, FVRI decreased by 47% and 56% before, and by 61% and 67% after GSH (p = 0.003). Glutathione also elevated cGMP levels in the femoral vein during ACH infusion from 17.6 ± 3 to 23.3 ± 3 pmol/ml (p = 0.006). Augmentation of ACH responses was only observed in patients with depressed endothelial function. Glutathione did not influence endothelium-independent vasodilation with either NO donor.

CONCLUSIONS

Thiol supplementation with GSH selectively improves human endothelial dysfunction by enhancing NO activity.

Abbreviations and Acronyms   ACH = acetylcholine   ANOVA = analysis of variance   cGMP = cyclic guanosine monophosphate   CV = coefficient of variation   FVRI = femoral vascular resistance index   GSH = glutathione   NO = nitric oxide   NTG = nitroglycerin   SH = sulfhydryl group

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