Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats

Yen Mei Lee, Pao Yun Cheng, Su Fen Hong, Shu Ying Chen, Kwok Keung Lam, Joen Rong Sheu, Mao Hsiung Yen

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39 Citations (Scopus)


Heme oxygenase-1 (HO-1), an inducible stress protein, has been implicated in cytoprotection against oxidative stress in vitro and in vivo. Estrogens also have antioxidant effects. This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems. HO-1 and iNOS protein expression was induced by ovariectomy (Ovx) and was extremely high 2-6 weeks after Ovx compared with the sham-operated group. Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats. 17β-Estradiol (E2) replacement reversed these changes in rats after Ovx. Long-term treatment with the antioxidant tempol significantly inhibited HO-1 and iNOS expression. The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1. Oxidized glutathione in the hearts of Ovx rats increased gradually, with significant elevation at 3-6 weeks after Ovx compared with the sham-operated group, whereas plasma levels of NO metabolites were significantly reduced 4-6 weeks after Ovx. Treatment with the HO inhibitor zinc protoporphyrin IX blocked HO-1 induction, but significantly increased the plasma levels of NO metabolites. In conclusion, HO-1 is induced by oxidative stress resulting from E2 depletion. The NO/iNOS system contributes to the induction of HO-1, which may subsequently suppress iNOS activity to modulate vasculoprotective effects after menopause.

Original languageEnglish
Pages (from-to)108-117
Number of pages10
JournalFree Radical Biology and Medicine
Issue number1
Publication statusPublished - Jul 1 2005


  • Estrogen
  • Heme oxygenase-1
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Ovariectomy
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology (medical)
  • Biochemistry


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