Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice.
This study investigated the role of endogenous nitric oxide (NO) in the progression of atherosclerosis in apolipoprotein E-deficient [apoE-knockout (KO)] mice. Mice were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) an inhibitor of nitric oxide synthase (NOS) or with the NOS substrate L-arginine for 8 wk. L-NAME treatment resulted in a significant inhibition of NO-mediated vascular responses and a significant increase in the atherosclerotic plaque/surface area in the aorta of apoE-KO mice. L-arginine treatment had no influence on endothelial function and did not alter lesion size. Mean arterial blood pressure and serum lipid levels were not altered by the treatments. At the beginning of the study impairment in endothelial function was only apparent in the case of N(G)-nitro-L-arginine-induced, NO-mediated contraction, whereas ACh-induced, NO-mediated relaxation was not different between age-matched apoE-KO and C57Bl/6J mice. After the 8-wk treatment with the NOS inhibitor, both NO-mediated responses were significantly inhibited. The acceleration in lesion size concomitant to the severely impaired NO-mediated responses indicates that lack of endogenous NO is an important progression factor of atherosclerosis in the apoE-KO mouse.
Kauser
K
K
Cardiovascular Research, Berlex Biosciences, Richmond, California 94804-0099, USA. katalin_kauser@berlex.com
da Cunha
V
V
Fitch
R
R
Mallari
C
C
Rubanyi
G M
GM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001120:Arginine / Q000494:pharmacology; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D008055:Lipids; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester