Endothelium-dependent relaxation of rabbit atherosclerotic aorta was not restored by control of hyperlipidemia: the possible role of peroxynitrite (ONOO-)

Toshio Hayashi, Kazuyoshi Yamada, Teiji Esaki, Hatsuyo Kano, Yukako Asai, Navin Kumar Thakur, Muthuvel Jayachandran, Daigo Sumi, Akihisa Iguchi

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)349-363
Number of pages15
JournalAtherosclerosis
Volume147
Issue number2
DOIs
StatePublished - Sep 9 1999

Keywords

  • (ONOO), peroxynitrite
  • Arteriosclerosis
  • Hypercholesterolemia
  • Immunohistochemistry
  • NO, nitric oxide
  • NOS, nitric oxide synthase
  • Nitric oxide
  • Peroxynitrite
  • Regression
  • e-NOS, endothelial nitric oxide synthase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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