L-arginine supplementation in hypercholesterolemic rabbits normalizes leukocyte adhesion to non-endothelial matrix

Abstract

L-arginine slows the development of atheromatous lesions, improves endothelium-dependent relaxation, and reduces the vascular superoxide anion production in hypercholesterolemic rabbits. These beneficial effects have been attributed to L-arginine-dependent formation of nitric oxide within the endothelial layer; a direct effect of L-arginine on other cells, however, has not been investigated. We hypothesised that in hypercholesterolemia L-arginine also specifically acts via a direct inhibitory effect on leukocytes, without affecting endothelial cells. The action of L-arginine was compared to vitamine E and the HMG CoA reductase inhibitor lovastatin which are known to attenuate progression of atherosclerosis. Rabbits were fed cholesterol enriched diet and from week five on lovastatin (10 mg/ day), vitamine E (300 mg/ d) or L-arginine (2% in drinking water) were given. After 16 weeks, blood cholesterol concentration was determined and leukocyte adhesion to cotton wool was measured. In order to exclude any endothelium-mediated effects an adhesion assay to endothelial cells was avoided. Cholesterol-enriched diet increased plasma cholesterol concentration (19 ± 3 vs. 1427 ± 117 mg/ dl). Cholesterol levels were not affected by L-arginine (1344 ± 163 mg/ dl) or vitamine E (1312 ± 243 mg/ dl). Lovastatin treatment reduced cholesterol concentration by 35% as compared to the cholesterol group (899 ± 51, p < 0.05 vs. cholesterol). Cholesterol diet significantly increased leukocyte adhesion to cotton wool (16 ± 3% vs 27 ± 4%, p < 0.05). Lovastatin or vitamine E had no effect on leukocyte adhesion (31 ± 4%, 39 ± 5), whereas L-arginine completely normalized adhesion (8.8 ± 3%). Conclusion: Rabbits fed high cholesterol diet have increased leukocyte adhesion, which is not affected by lovastatin or vitamine E treatment, but prevented by L-arginine supplementation. A direct inhibitory effect of L-arginine on leukocyte adhesion may contribute to the beneficial effects observed with this substance.