Coronary endothelial dysfunction after ischemia and reperfusion and its prevention by ischemic preconditioning.
In the coronary circulation, when reperfusion follows ischemia, endothelial dysfunction occurs. This is characterized by a reduced endothelial release of nitric oxide and by an increased release of reactive oxygen species and endothelin. The reduced availability of nitric oxide leads to the adhesion of neutrophils to the vascular endothelium, platelet aggregation and, with the contribution of endothelin, vasoconstriction, which are responsible for the "no-reflow" phenomenon. Neutrophil adhesion is followed by the release of the superoxide anion from neutrophils and endothelial cells. Preconditioning limits the endothelial damage by ischemia-reperfusion. A relevant role is attributed to the increased endothelial release of nitric oxide, while that of adenosine is controversial. Another effect of preconditioning on the coronary vasculature is the acceleration of vasodilation in reactive hyperemia after a brief coronary occlusion. The acceleration is prevented if myocardial protection is achieved by means of the activation of the mitochondrial adenosine triphosphate sensitive potassium channels by diazoxide and persists when ischemic preconditioning is induced after blockade of the same channels by 5-hydroxydecanoate.
Pagliaro
Pasquale
P
Department of Biological and Clinical Sciences, University of Turin, Turin, Italy. pasquale.pagliaro@unito.it
Chiribiri
Amedeo
A
Mancardi
Daniele
D
Rastaldo
Raffaella
R
Gattullo
Donatella
D
Losano
Gianni
G
D000241:Adenosine / Q000378:metabolism / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000241:Adenosine