Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability

OBJECTIVES We investigated whether glutathione (GSH), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endo thelium-dependent vasomotion and NO activity in atherosclerosis. BACKGROUND Endothelial dysfunction and reduced NO activity are associated w ith atherosclerosis and its clinical manifestations such as unstable angina . METHODS In the femoral circulation of 17 patients with atherosclerosis or i ts risk factors, endothelium-dependent vasodilation with acetylcholine (ACH ), and endothelium-independent vasodilation with nitroglycerin and sodium n itroprusside were studied before and after GSH. In 10 patients, femoral vei n plasma cyclic guanylate monophosphate (cGMP) levels were measured during an infusion of ACH before and after GSH. Femoral artery flow velocity was m easured using a Doppler flow wire and the resistance index (FVRI) calculate d as mean arterial pressure divided by flow velocity. RESULTS Glutathione strongly potentiated AGH-mediated vasodilation; at the two doses, FVRI decreased by 47% and 56% before, and by 61% and 67% after G SH (p = 0.003). Glutathione also elevated cGMP levels in the femoral vein d uring ACH infusion from 17.6 +/- 3 to 23.3 rt 3 pmol/ml (p = 0.006). Augmen tation of ACH responses was only observed in patients with depressed endoth elial function. Glutathione did not influence endothelium-independent vasod ilation with either NO donor. CONCLUSIONS Thiol supplementation with GSH selectively improves human endot helial dysfunction by enhancing NO activity. (C) 1999 by the American Colle ge of Cardiology.