Ischemic preconditioning prevents endothelial dysfunction, P-selectin expression, and neutrophil adhesion by preventing endothelin and O2-generation in the post-ischemic guinea-pig heart

• Autorzy: Duda M. , Czarnowska E. , Kurzelewski M. , Konior A. , Beresewicz A.
• Języki publikacji: EN

Abstrakty

EN

Evidence indicates that ischemia/reperfusion (IR) results in endothelial dysfunction and neutrophil adhesion in the post-ischemic myocardium and that ischemic preconditioning (IPC), superoxide dismutase (SOD), and anti-endothelin-1 (ET-1) interventions prevent these effects. We tested the hypothesis that ET-1-induced superoxide (O2-) generation mediates endothelial injury and neutrophil accumulation in the IR heart, that IPC protects the endothelium and prevents the adhesion by attenuating post-ischemic ET-1, and thus O2-, generation, and that the mitochondrial ATP-dependent potassium channel (mKATP) triggers the IPC-induced protection. Langendorff-perfused guinea-pig hearts were subjected either to 30 min ischemia/35 min reperfusion (IR) or were preconditioned prior to IR with three cycles of either 5 min ischemia/5 min reperfusion or 5 min infusion/5 min wash-out of mKATP opener diazoxide (0.5 µM). Neutrophils were infused to the hearts at 15-25min of the reperfusion. Coronary flow responses to acetylcholine (ACh) and nitroprusside (SNP) served as measures of endothelium-dependent and -independent vascular function, respectively. Myocardial outflow of ET-1 and O2-, P-selectin expression, neutrophil adhesion and functional recoveries were followed during reperfusion. IR augmented ET-1 and O2- outflow, P-selectin expression, and neutrophil adhesion, and impaired ACh response. These effects were attenuated or prevented by IPC and diazoxide, and 5-hydroxydecanoate (a selective mKATP blocker) abolished the effects of IPC and diazoxide. SOD (150 U/ml) and tezosentan (5 nM, a mixed ET-1-receptor antagonist) mimicked the effects of IPC, although they had no effect on the ET-1 generation. The preventive effect of IPC, SOD and tezosentan on P-selectin expression preceded their effect on neutrophil adhesion. These data suggest that in guinea-pig heart: (i) ET-1-induced O2- generation mediates the post-ischemic endothelial dysfunction, P-selectin expression and neutrophil adhesion; (ii) IPC and diazoxide afford protection by attenuating the ET-1, and thus O2- generation; (iii) the mKATP opening triggers the IPC protection; (iv) endothelial injury promotes post-ischemic neutrophil adhesion, but not vice versa.

Słowa kluczowe

EN

post-ischaemic heart; guinea pig; heart; ischaemic preconditioning; neutrophil adhesion; endothelial dysfunction

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2006
• Tom: 57
• Numer: 4
• Opis fizyczny: p.553-569,fig.,ref.

Twórcy

autor

Duda M.

• Medical Centre of Postgraduate Education, Marymoncka 99, 01-813 Warsaw, Poland

autor

Czarnowska E.

autor

Kurzelewski M.

autor

Konior A.

autor

Beresewicz A.