Document Detail


Endothelial NO Synthase (eNOS) phosphorylation regulates coronary diameter during ischemia-reperfusion in association with oxidative stress.
MedLine Citation:
PMID:  16036323     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The link between endothelial nitric oxide synthase (eNOS) activation and vascular diameter during ischemia-reperfusion was investigated in the rat heart. After short (<30 min) and long (>45 min) time of ischemia conferred by coronary artery occlusion of the rats, reperfusion caused dilatation and constriction of arterioles, respectively. Partial oxygen pressure (pO2) measurement of the heart by the electrode confirmed the hyper-perfusion and no-reflow phenomena during reperfusion, as well as myocardial ischemia. The vascular diameter was correlated with phosphorylation of Akt and serine 1177 residue of eNOS, and formation of NO-bound guanylate cyclase (GC) by immuoflorescence study. Western blotting confirmed the phosphorylation of eNOS-Ser1177 depending on ischemia time. The constriction during reperfusion after 45 min of ischemia is supposedly caused by the inhibition of Akt-mediated eNOS-Ser1177 phosphorylation, which was suppressed by a PKC inhibitor chelerythrine, or ROS scavengers N-2-mercaptopropionyl glycine (MPG) and 4,5-Dihydroxy-1, 3-benzenedisulfonic acid disodium salt (Tiron). However, an endothelin receptor antagonist BQ123 alleviated the vasoconstriction by increasing NO availability but not eNOS-Ser1177 phosphorylation. Thus, vascular patency is correlated with eNOS-Ser1177 phosphorylation in association with ROS, and PKC during reperfusion. Endothelin inhibits vasodilatation by reducing NO availability during reperfusion.
Authors:
Sumihisa Hoshino; Yousuke Kikuchi; Makoto Nakajima; Hiroko Kimura; Shingo Tsuyama; Koichi Uemura; Ken-Ichi Yoshida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical research     Volume:  39     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-07-22     Completed Date:  2005-09-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  481-9     Citation Subset:  IM    
Affiliation:
Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Coronary Vessels / enzymology*
Endothelins / metabolism
Enzyme Activation / physiology
Enzyme Inhibitors / pharmacology
Fluorescent Antibody Technique
Heart / drug effects
Male
Myocardium / enzymology,  pathology
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type III
Oxidative Stress / physiology*
Phosphorylation
Protein Kinase C / metabolism
Rats
Reactive Oxygen Species / metabolism
Reperfusion Injury / enzymology*
Vasoconstriction / drug effects,  physiology*
Chemical
Reg. No./Substance:
0/Endothelins; 0/Enzyme Inhibitors; 0/Reactive Oxygen Species; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat; EC 2.7.11.13/Protein Kinase C

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