Endothelial protection from reperfusion injury by ischemic preconditioning and diazoxide involves a SOD-like anti-O2 mechanism

• Autorzy: Maczewski M. , Duda M. , Pawlak W. , Beresewicz A.
• Języki publikacji: EN

Abstrakty

EN

Cardiac ischemia/reperfusion leads to coronary endothelial dysfunction, mediated by superoxide anion (O2-), but not hydroxyl radical (.OH). Ischemic preconditioning and mitochondrial ATP-dependent potassium channel opener (diazoxide) protect endothelium in the mechanism involving attenuation of O2- burst at reperfusion. We hypothesize that the endothelial protection involves upregulation of myocardial anty-O2- defense. Langendorff-perfused guinea-pig hearts were subjected to global ischemia/reperfusion (IR) or were preconditioned prior to IR with three cycles of ischemia/reperfusion (IPC) or infusion/washout of 0.5 µM diazoxide. Coronary flow responses to acetylcholine were measures of endothelium-dependent vascular function. Myocardial outflow of O2- and of .OH during reperfusion and myocardial activities of superoxide dismutase (SOD) and catalase were measured. IR impaired acetylcholine response and augmented cardiac O2- and .OH outflow. IPC, diazoxide, and SOD (150 IU/ml) attenuated O2- outflow, increased .OH outflow and protected endothelium. There were no differences in Cu/Zn-SOD, Mn-SOD and catalase activities between sham-perfused and IR hearts and only catalase activity was increased in the IPC hearts. We speculate that: (i) IPC and diazoxide endothelial protection involves activation of some SOD-like anti-O2- mechanism resulting in attenuation of O2- burst and increase in .OH burst, (ii) improved SOD activity might have not been detected because it was confined to a small, although functionally important, enzyme fraction, like that bound to the endothelial glycocalyx.

Słowa kluczowe

EN

superoxide dismutase; post-ischaemic endothelial dysfunction; catalase; hydroxyl radical; diazoxide; ischaemic preconditioning; superoxide anion

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2004
• Tom: 55
• Numer: 3
• Opis fizyczny: p.537-550,fig.,ref.

Twórcy

autor

Maczewski M.

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

autor

Duda M.

autor

Pawlak W.

autor

Beresewicz A.