l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta

Diminished bioavailability of nitric oxide is crucial in endothelial dysfunction and the development of atherosclerosis. Several studies have found that l-arginine as a nitric oxide (NO) donor has beneficial effect in prevention of atherosclerosis, but the mechanism is not completely known. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased inducible NOS (iNOS) expressions might be involved in the preventive effects of l-arginine in hypercholesterolemic rabbits.

Seventeen male rabbits were divided randomly in two groups. They received rabbits chow supplemented with 1% cholesterol (group 1, n=8) and the other group received also l-arginine (3% in drinking water) (group 2, n=9) for 1 month. Blood samples were obtained before and after the experiment. At the end of experiment, the aortas were harvested. The serum levels of cholesterol and low-density lipoproteins (LDL) were measured. The intima/media thickness (IMT) ratio was measured and the determination of fatty streak formation was done with the aid of light microscopy. eNOS and iNOS expression in aorta were studied with immuohistochemistery.

The IMT ratio in first group having fatty streaks was 0.287±0.15. No fatty streak lesion was detected in l-arginine-treated group. The results also indicated that eNOS expression (intensity) in aortas was significantly higher in l-arginine-treated group (group 1: 13.62±2.7 and group 2: 21.77±2.8; p<0.05), but no significant difference was observed for iNOS expression between the groups.

The expression of eNOS plays an important role in the protection of the vessel wall from atherosclerosis. l-Arginine in drinking water has a beneficial effect in the enhancement of eNOS protein expression.