Endothelium-dependent relaxation of rabbit atherosclerotic aorta was not restored by control of hyperlipidemia: the possible role of peroxynitrite (ONOO(-)).
We determined the role of ONOO(-) in nitric oxide (NO) mediated vascular response in atherosclerosis and regression following removal of dietary cholesterol. The effect of ONOO(-) on NO-mediated vascular responses was examined in vitro. Basal and stimulated NO release was estimated by an NO-selective electrode as well as vascular response and the plasma NO metabolites. An immunohistochemical study was also carried out. Responses were compared in normal controls, atherosclerotic rabbits fed 1% cholesterol diet for 6 or 9 weeks (atherosclerotic group) and animals fed a normal diet for 6-36 weeks after the high cholesterol diet for 6 or 9 weeks (regression group). ONOO(-) impaired the basal and acetylcholine-stimulated NO release, but did not affect endothelium-independent relaxation. After 15 weeks on a normal diet, the acetylcholine-stimulated and basal NO-mediated relaxation, which was diminished in the aorta induced by 6 weeks high cholesterol diet, became restored. However, the vascular response in the 9 weeks high cholesterol diet group did not return to normal after 36 weeks on a normal diet. iNOS was observed in atherosclerotic plaques in atherosclerotic and regression groups along with ONOO(-) in the 9 weeks high cholesterol diet group, but not in the 6 weeks group. Conclusively, ONOO(-) can play a role in impairment of NO-mediated vascular response during the regression of dietary cholesterol-induced atherosclerosis, not in the initiation of atherosclerosis.
Hayashi
T
T
Department of Geriatrics, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Japan. hayashi@med.nagoya-u.ac.jp
Yamada
K
K
Esaki
T
T
Kano
H
H
Asai
Y
Y
Kumar Thakur
N
N
Jayachandran
M
M
Sumi
D
D
Iguchi
A
A
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D046508:Culture Techniques; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006949:Hyperlipidemias / Q000378:metabolism* / Q000628:therapy; D007150:Immunohistochemistry; D008297:Male; D009566:Nitrates / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016877:Oxidants / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D012016:Reference Values; D015203:Reproducibility of Results; D014664:Vasodilation / Q000187:drug effects
D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine