Effects of L-arginine on atherogenesis and endothelial dysfunction due to secondhand smoke.
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.
Division of Cardiology, University of California, San Francisco, Moffit Hospital Room 1186, San Francisco, CA, USA. stuart.hutchison@utoronto.ca
S J
SJ
Hutchison
K
K
Sudhir
R E
RE
Sievers
B Q
BQ
Zhu
Y P
YP
Sun
T M
TM
Chou
K
K
Chatterjee
P C
PC
Deedwania
J P
JP
Cooke
S A
SA
Glantz
W W
WW
Parmley
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000209:etiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D011817:Rabbits; D014028:Tobacco Smoke Pollution; D017539:Tunica Intima / Q000473:pathology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology
D008055:Lipids; D014028:Tobacco Smoke Pollution; D009569:Nitric Oxide; D001120:Arginine