Involvement of nitric oxide in ischemic preconditioning.
In ischemic preconditioning, nitric oxide (NO) limits the extension of a subsequent infarct and protects against ischemia/reperfusion-induced endothelial dysfunction, arrhythmias and myocardial stunning. The protective activity concerns both the first and the second window of protection. The antiarrhythmic effect is attributed to microvessel dilation and to the production of cyclic guanosine monophosphate in the myocardium. The limitation of the infarct size is likely to depend on the opening of the mitochondrial adenosine triphosphate-sensitive potassium channels, to which NO participates via the activation of a protein kinase C (PKC). The endothelial protection involves an NO-mediated reduction in neutrophil adherence to the coronary endothelium and platelet aggregation and is accompanied by an enhanced response to vasodilator stimuli. During preconditioning ischemia, NO is released from the coronary endothelium as a result of bradykinin-induced activation of B2 endothelial receptors. In addition to the early protection, endothelium-derived NO is also responsible for a signaling cascade which leads to the activation of myocardial inducible NO synthase, which in turn is responsible for the release of NO involved in the delayed protection. The signaling cascade includes the activation of PKC-epsilon, tyrosine kinase and some mitogen-activated protein kinases. It has been suggested that the activation of PKC-epsilon is mediated by peroxynitrite produced by the combination of NO and the superoxide anion, the latter being generated during reperfusion which follows preconditioning ischemia.
Pagliaro
P
P
Department of Clinical and Biological Sciences, University of Turin, Italy. pasquale.pagliaro@unito.it
Gattullo
D
D
Rastaldo
R
R
Losano
G
G
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*
D009569:Nitric Oxide