Effects of L-arginine on atherogenesis and endothelial dysfunction due to secondhand smoke

Secondhand smoke (SHS) and hypercholesterolemia increase cardiovascular ris k; We hypothesized that L-arginine, the precursor of nitric oxide (NO), mig ht 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 hypercholesterolemi c rabbits. Eight normal rabbits served as controls, Acetylcholine- and nitr oglycerin-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 ba sal (P=0.005) and stimulated (P<0.0005) production of NOs. SHS increased in timal 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 relax ation(P=0.001) and attenuated SHS-induced endothelial dysfunction (P=0.007) and atherogenesis (P=0.001). Basal production of nitrogen oxides correlate d inversely; with intimal lesion area (r=-0.66; P<0.0005) and stimulated pr oduction of NOs correlated with endothelium-dependent relaxation (r=-0.66; P<0.001). SHS causes endothelial dysfunction and increased adrenergic respo nsiveness and atherogenesis in hypercholesterolemic rabbits. Chronic dietar y supplementation with the NO precursor L-arginine mitigates these effects. The adverse vascular consequences of SHS appear to be mediated via deleter ious effects on endothelial function.