Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability.
OBJECTIVE
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 divided by 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.
Prasad
A
A
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Andrews
N P
NP
Padder
F A
FA
Husain
M
M
Quyyumi
A A
AA
D000109:Acetylcholine / Q000494:pharmacology; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D005996:Nitroglycerin; D005978:Glutathione; D006152:Cyclic GMP; D000109:Acetylcholine