Chronic L-arginine supplementation improves endothelial cell vasoactive functions in hypercholesterolemic and atherosclerotic monkeys.
Chronic exposure to L-arginine results in regression of atherosclerotic lesions and reversal of endothelial dysfunction. We investigated whether chronic L-arginine supplementation induces regression of atherosclerotic lesions and reversal of endothelial dysfunction in atherogenic rhesus monkeys and the mechanism which leads to these effects. About 12 male rhesus monkeys were fed 1% cholesterol and 18 g butter for 6 months to create an experimental model of hypercholesterolaemia and atherosclerosis (Group I) and 12 monkeys were fed standard stock diet for 6 months (Group II). After, 6 months these two groups were further divided into 2 sub-groups which in addition to their respective diets were fed 2.5% L-arginine in drinking water for additional 6 months (Group III and Group IV). Systemic nitric oxide (NO) formation was assessed as plasma nitrite and cGMP formation every 3 months. Oxygen free radical (OFR) generation and malondialdehyde production as an index of lipid peroxidation were determined. Changes in isometric tension were compared in isolated ring segments of thoracic aorta from normal and hypercholesterolemic animals. Cholesterol feeding progressively reduced plasma nitrite and cGMP generation (p < 0.05). Dietary L-arginine partly restored the levels of plasma nitrite and cGMP (p < 0.05) but did not change plasma cholesterol levels. L-arginine significantly reduced aortic intimal thickening, blocked the production of carotid and coronary intimal plaques and completely preserved endothelium-dependent vasodilator function. Further, L-arginine significantly inhibited generation of the reactive oxygen species (ROS) generation and lipid peroxidation. Chronic oral supplementation with L-arginine blocks the progression of plaques via restoration of nitric oxide synthase substrate availability and reduction of vascular oxidative stress.
Dhawan
Veena
V
Departments of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India. veenad2001@yahoo.com
Handu
S S
SS
Nain
Chandra Kanwal
CK
Ganguly
Nirmal Kumar
NK
D000818:Animals; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation; D008253:Macaca mulatta; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000097:blood
D002791:Cholesterol, Dietary; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP