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

Abstract

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 (O 2 − ) and ACE activity. The increased O 2 − 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 O 2 − 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.