Mediation of L-arginine-induced retardation of hypercholesterolemic atherosclerosis in rabbits by antioxidant mechanisms

Smooth muscle cell proliferation is a characteristic feature of atheroscler osis. Reactive oxygen species are suggested to play a role in smooth muscle cell proliferation. Nitric oxide (NO) is known to inhibit smooth muscle ce ll proliferation. But it is not known if NO can retard the development of h ypercholesterolemic atherosclerosis. We hypothesized that L-arginine, the p recursor of NO, may retard the development of hypercholesterolemic atherosc lerosis through antioxidant mechanisms. We, therefore, investigated the eff ects of L-arginine on the high cholesterol diet-induced changes in the deve lopment of atherosclerosis in the female rabbit aorta. The indices studied included blood lipids, aortic tissue malondialdehyde (MDA); a measure of li pid peroxidation, aortic tissue chemiluminescence (CL), a measure of antiox idant reserve and activity of antioxidant enzymes [superoxide dismutase (SO D), catalase and glutathione peroxidase (GSH-Px)]. Animals were assigned to one of 3 groups: group I, regular rabbit diet; group II, 1% cholesterol ad ded, group III, 1% cholesterol + L-arginine (2.5%) added. Blood samples wer e collected before and after 4 weeks and 10 weeks on the respective diets. The aorta was removed at the end of 10 weeks for assessment of atherosclero tic plaques and biochemical changes. There was an increase in the total ser um cholesterol in groups II and III. Aortic MDA, CL, catalase, and GSH-Px i ncreased in groups II as compared to group I and decreased in group III as compared to group II. Ninety-five percent of the intimal surface of aorta w as covered with atherosclerotic plaques in group II but only 60% was covere d in group III. This 35% inhibition of hypercholesterolemic atherosclerosis by L-arginine was associated with increase in the antioxidative reserve (a s measured by aortic tissue chemiluminescence) without change in serum chol esterol levels. These results suggest that hypercholesterolemic atheroscler osis in rabbits is associated with oxidative stress, and that Larginine may retard the development of hypercholesterolemic atherosclerosis through ant ioxidant mechanisms. (C) 1999 Elsevier Science Inc.