Pathogenic Role of Oxidative Stress in Vascular Angiotensin-Converting Enzyme Activation in Long-Term Blockade of Nitric Oxide Synthesis in Rats

Makoto Usui, Kensuke Egashira, Shiro Kitamoto, Masamichi Koyanagi, Makoto Katoh, Chu Kataoka, Hiroaki Shimokawa, Akira Takeshita

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100 Citations (Scopus)

Abstract

Inhibition of nitric oxide (NO) synthesis with N ω-nitro-L-arginine methyl ester (L-NAME) activates vascular angiotensin-converting enzyme (ACE) and causes oxidative stress. We investigated the role of oxidative stress in the pathogenesis of ACE activation in rats. Studies involved aortas of rats receiving no treatment, L-NAME, L-NAME plus L-arginine, or L-NAME plus an antioxidant drug (N-acetylcysteine, allopurinol, or ebselen) for 7 days. L-NAME significantly increased oxidative stress (O2) and ACE activity. The increased O2 production was normalized by removal of endothelium. Immunohistochemistry showed the increased ACE activity in the endothelial layer. Treatment with antioxidant drugs did not affect the L-NAME-induced increase in systolic arterial pressure but did prevent increases in vascular O2 production and ACE activity. These results implicate oxidative stress in the pathogenesis of vascular ACE activation in rats with long-term inhibition of NO synthesis. The observed effects of antioxidant drugs on ACE activation do not appear to involve the hypertension induced by L-NAME.

Original languageEnglish
Pages (from-to)546-551
Number of pages6
JournalHypertension
Volume34
Issue number4
DOIs
Publication statusPublished - Oct 1999

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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