Pathogenic role of oxidative stress in vascular angiotensin-converting enzyme activation in long-term blockade of nitric oxide synthesis in rats.
Inhibition of nitric oxide (NO) synthesis with N(omega)-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.
Usui
M
M
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Egashira
K
K
Kitamoto
S
S
Koyanagi
M
M
Katoh
M
M
Kataoka
C
C
Shimokawa
H
H
Takeshita
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
D000975:Antioxidants; D004791:Enzyme Inhibitors; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D007703:Peptidyl-Dipeptidase A; D019331:NG-Nitroarginine Methyl Ester