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(Hypertension. 1999;34:546-551.)
© 1999 American Heart Association, Inc.

Scientific Contributions

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

Presented in part as an abstract (Circulation. 1998;98:I–311) at the 71st Scientific Sessions of the American Heart Association, November 8–11, 1998, Dallas, Tex.

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

From the Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University Faculty of Medicine, Fukuoka, Japan.

Correspondence to Kensuke Egashira, MD, Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail egashira{at}cardiol.med.kyushu-u.ac.jp

Abstract—Inhibition of nitric oxide (NO) synthesis with N-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.

Key Words: nitric oxide • stress, oxidative • anions • angiotensin-converting enzyme • remodeling

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