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

L-arginine slows the development of atheromatous lesions, improves endothel ium-dependent relaxation, and reduces the vascular superoxide anion product ion in hypercholesterolemic rabbits. These beneficial effects have been att ributed to L-arginine-dependent formation of nitric oxide within the endoth elial 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, witho ut affecting endothelial cells. The action of L-arginine was compared to vi tamine E and the HMG CoA reductase inhibitor lovastatin which are known to attenuate progression of atherosclerosis. Rabbits were fed cholesterol enri ched diet and from week five on lovastatin (10mg/day), vitamine E (300mg/d) or L-arginine (2% in drinking water) were given. After 16 weeks, blood cho lesterol concentration was determined and leukocyte adhesion to cotton wool was measured. In order to exclude any endothelium-mediated effects an adhe sion assay to endothelial cells was avoided. Cholesterol-enriched diet incr eased plasma cholesterol concentration (19+/-3 vs. 1427+/-117 mg/dl). Chole sterol levels were not affected by L-arginine (1344+/-163mg/dl) or vitamine E (1312+/-243mg/dl). Lovastatin treatment reduced cholesterol concentratio n by 35% as compared to the cholesterol group (899+/-51, p<0.05 vs. cholest erol). Cholesterol diet significantly increased leukocyte adhesion to cotto n 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 norm alized adhesion (8.8+/-3%). Conclusion: Rabbits fed high cholesterol diet h ave increased leukocyte adhesion, which is not affected by lovastatin or vi tamine E treatment, but prevented by L-arginine supplementation. A direct i nhibitory effect of L-arginine on leukocyte adhesion may contribute to the beneficial effects observed with this substance.