DISCORDANT EFFECTS OF DIETARY L-ARGININE ON VASCULAR STRUCTURE AND REACTIVITY IN HYPERCHOLESTEROLEMIC RABBITS

We investigated the effect of dietary supplementation of L-arginine (L -Arg), the precursor of endothelial nitric oxide (NO), on endothelium- dependent and endothelium-independent vascular responses, as well as v ascular structure, in the abdominal aorta of hypercholesterolemic rabb its. Rabbits were fed (a) normal rabbit chow, (b) 1% cholesterol diet, or (c) 1% cholesterol diet supplemented with 2.25% L-Arg HCl in drink ing water. After 10 weeks, the abdominal aorta was harvested for study of vascular reactivity and histomorphometry. L-Arg did not affect ser um cholesterol levels. Histomorphometric analysis demonstrated an eigh tfold reduction in intimal thickening in the abdominal aorta of the ar ginine-supplemented hypercholesterolemic rabbits. By contrast, the eff ects on vascular reactivity were subtle. Contraction to norepinephrine (NE) was not altered by hypercholesterolemia or L-Arg. Contraction to acetylcholine (ACh) was increased in hypercholesterolemic animals; th is was normalized by dietary arginine supplementation. Relaxation to n itroglycerin (NTG) was not altered by hypercholesterolemia but was att enuated in the arginine supplemented rabbits. Endothelium-dependent re laxation to ACh was impaired in both hypercholesterolemic groups. Diet ary L-Arg has a dramatic antiatherogenic effect in hypercholesterolemi c rabbits. This effect is associated with rather slight changes in vas cular reactivity that are suggestive of a slight increase in NO elabor ation by the endothelium. The discordance between the effects of dieta ry arginine on vascular structure and reactivity suggests that the ant iatherogenic effects of the NO precursor may not be mediated entirely by its effect on the endothelium.