[Nitric oxide/heme oxygenase-1 mediates the antioxidant effect of ACEI in rat aortic rings].
To examine the effect of angiotensin-converting enzyme inhibitor (ACEI) on hydrogen peroxide (H(2)O(2))-induced decrease in contraction of isolated rataortic rings, and to investigate its mechanisms.



The thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured.



(1) After incubation with captopril (an ACEI with sulfhydryl groups) or perindoprilate (an ACEI without sulfhydryl groups), the decrease in contraction response to PE was prevented in arteries which were pretreated with 300 micromol/L H(2)O(2). (2) Captopril enhanced the HO-1 activity of thoracic aorta. After inhibition of HO-1 activity by ZnPP IX, the protection effect of captopril was abrogated. Hemin (an inducer of HO-1) and bilirubin (a product of HO-1) could mimic the antioxidative effect of captopril. (3) Both L-NAME (an inhibitor of NOS) and methylene blue (an inhibitor of GC) could abolish the protective effect of captopril. (4) SNAP could protect aortic rings against H(2)O(2) attack, and ZnPP IX could cancel the effect of SNAP.



Both ACEI with or without sulfhydryl groups could prevent the H(2)O(2) induced decrease in contraction responses to PE in intact aortic rings. The increase of NO and activation of HO-1 might be involved in the mechanism.
Zhu
Li
L
Department of Physiology, College of Medicine, Zhejiang University, Hangzhou 310058, China.
Shen
Yue-Liang
YL
Xu
He-Jing
HJ
Wang
Yang
Y
Chen
Ying-Ying
YY
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001663:Bilirubin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D011524:Protoporphyrins; C110881:S-nitro-N-acetylpenicillamine; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D002216:Captopril; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D010396:Penicillamine; D001663:Bilirubin; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester