CHRONIC DIETARY L-ARGININE PREVENTS ENDOTHELIAL DYSFUNCTION SECONDARYTO ENVIRONMENTAL TOBACCO-SMOKE IN NORMOCHOLESTEROLEMIC RABBITS

Our goal was to determine whether environmental tobacco smoke causes e ndothelial dysfunction in the absence of hypercholesterolemia and whet her such an effect can be prevented by supplementation with L-arginine . Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously de monstrated that environmental tobacco smoke causes endothelial dysfunc tion and atherosclerosis in rabbits with diet-induced hypercholesterol emia and atherosclerosis and that chronic dietary L-arginine supplemen tation prevents this, The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chamber s for 10 weeks) were examined with a 2x2 design in 32 rabbits fed a no rmal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin- induced vasorelaxation were assessed in aortic rings precontracted wit h phenylephrine. Endothelial L-arginine levels were measured by chroma tography. Chronic L-arginine supplementation increased serum (P<.001) and endothelial (P=.003) L-arginine levels. Environmental tobacco smok e reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P=.04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P=.06). Ne ither environmental tobacco smoke nor L-arginine influenced A23187-ind uced relaxation nor endothelium-independent nitroglycerin-induced rela xation. Endothelial dysfunction secondary to environmental tobacco smo ke may occur in the absence of diet-induced hypercholesterolemia and a therosclerosis. Chronic dietary supplementation with a nitric oxide do nor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, poss ibly through substrate loading of the nitric oxide pathway.