Heart Failure Reviews

, Volume 7, Issue 4, pp 391–405 | Cite as

Nitric Oxide and Cardioprotection During Ischemia-Reperfusion

  • Bodh I. Jugdutt


Coronary artery reperfusion is widely used to restore blood flow in acute myocardial infarction and limit its progression. However, reperfusion of ischemic myocardium results in reperfusion injury and persistent ventricular dysfunction even when achieved after brief periods of ischemia. Normally, small amounts of nitric oxide (NO) generated by endothelial NO synthase (eNOS) regulates vascular tone. Ischemia-reperfusion triggers the release of oxygen free radicals (OFRs) and a cascade involving endothelial dysfunction, decreased eNOS and NO, neutrophil activation, increased cytokines and more OFRs, increased inducible NO synthase (iNOS) and marked increase in NO, excess peroxynitrite formation, and myocardial injury. Low doses of NO appear to be beneficial and high doses harmful in ischemia-reperfusion. eNOS knock-out mice confirm that eNOS-derived NO is cardioprotective in ischemia-reperfusion. iNOS overexpression increases peroxynitrite but did not cause severe dysfunction. Increased angiotensin II (AngII) after ischemia-reperfusion inactivates NO, forms peroxynitrite and produces cardiotoxic effects. Beneficial effects of angiotensin-converting-enzyme inhibition and AngII type 1 (AT1) receptor blockade after ischemia-reperfusion are partly mediated through AngII type 2 (AT2) receptor stimulation, increased bradykinin and NO. Interventions that enhance NO availability by increasing eNOS might be beneficial after ischemia-reperfusion.

nitric oxide ischemia-reperfusion peroxynitrite angiotensin nitroglycerin 


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© Kluwer Academic Publishers 2002

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  • Bodh I. Jugdutt

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