Effects of l -Arginine on Atherogenesis and Endothelial Dysfunction due to Secondhand Smoke

Abstract

Abstract —Secondhand smoke (SHS) and hypercholesterolemia increase cardiovascular risk. We hypothesized that l -arginine, the precursor of nitric oxide (NO), might protect against atherogenesis and endothelial dysfunction caused by SHS. The effects of l -arginine supplementation (2.25% solution ad libitum) and SHS (smoking chambers for 10 weeks) were examined in 32 hypercholesterolemic rabbits. Eight normal rabbits served as controls. Acetylcholine- and nitroglycerin-induced vasorelaxation was assessed in aortic rings precontracted with norepinephrine. Hypercholesterolemia increased intimal lesion area ( P =0.012), reduced endothelium-dependent relaxation ( P =0.009), and reduced basal ( P =0.005) and stimulated ( P <0.0005) production of NOs. SHS increased intimal lesion area ( P =0.01) norepinephrine-induced contraction ( P =0.001) and reduced endothelium-dependent relaxation ( P =0.02). SHS-induced increase in norepinephrine contraction was abolished by the inhibition of NO synthase and removal of endothelium. l -Arginine improved endothelium-dependent relaxation ( P =0.001) and attenuated SHS-induced endothelial dysfunction ( P =0.007) and atherogenesis ( P =0.001). Basal production of nitrogen oxides correlated inversely with intimal lesion area ( r =−0.66; P <0.0005) and stimulated production of NOs correlated with endothelium-dependent relaxation ( r =−0.66; P <0.001). SHS causes endothelial dysfunction and increased adrenergic responsiveness and atherogenesis in hypercholesterolemic rabbits. Chronic dietary supplementation with the NO precursor l -arginine mitigates these effects. The adverse vascular consequences of SHS appear to be mediated via deleterious effects on endothelial function.