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.
Hutchison
S J
SJ
Division of Cardiology, University of California, San Francisco, Moffit Hospital Room 1186, San Francisco, CA, USA. stuart.hutchison@utoronto.ca
Sudhir
K
K
Sievers
R E
RE
Zhu
B Q
BQ
Sun
Y P
YP
Chou
T M
TM
Chatterjee
K
K
Deedwania
P C
PC
Cooke
J P
JP
Glantz
S A
SA
Parmley
W W
WW
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