DIETARY ARGININE PREVENTS ATHEROGENESIS IN THE CORONARY-ARTERY OF THEHYPERCHOLESTEROLEMIC RABBIT

Objectives. This study was designed to test the hypothesis that long t erm oral supplementation of dietary L-arginine (to provide a sustained elevation of nitric oxide activity) would inhibit atherogenesis in hy percholesterolemic rabbits, as assessed by histomorphometric measureme nts. Background. Endothelium derived nitric oxide inhibits a number of processes that are critical in atherogenesis. Hypercholesterolemia re duces endothelial nitric oxide activity, and we postulate that this ma y promote atherogenesis. This reduction in nitric oxide activity can b e reversed acutely by intravenous infusion of L-arginine, the precurso r of nitric oxide. We show that dietary supplementation of L-arginine abrogates the development of cor onary atheroma in hypercholesterolemi c rabbits. Methods. Male New Zealand White rabbits were fed normal rab bit chow, 1% cholesterol chow or 1% cholesterol chow with dietary argi nine or methionine supplementation to increase their intake of these a mino acids sixfold. After 1 or 10 weeks of dietary intervention, the l eft main and left anterior descending coronary arteries were harvested for histologic study. Plasma cholesterol measurements were elevated t o the same degree in all groups of rabbits receiving the 1% cholestero l diet, whereas plasma arginine levels were doubled in the arginine tr eated group. High density lipoprotein (HDL) cholesterol values were no t affected by arginine treatment. Results. In rabbits receiving the 1% cholesterol diet, with or without methionine supplementation, light a nd electron micros copy revealed a marked increase from 1 to 10 weeks in the intimal accumulation of macrophages, associated with an increas e in tbe intimal area of the left main coronary artery. By contrast, i n arginine-treated hypercholesterolemic rabbits, there was a near abse nce of adherent monocytes and tissue macrophages and no progression of intimal thickness from 1 to 10 weeks. Conclusions. Dietary supplement s of L-arginine prevent intimal thickening in tbe coronary arteries of hypercholesterolemic rabbits. This antiatherogenic effect is not due to an alteration in plasma total cholesterol, HDL cholesterol or calor ic or nitrogen balance. The data are consistent with the hypothesis th at nitric oxide has antiatherogenic properties.