Endothelial protection from reperfusion injury by ischemic preconditioning and diazoxide involves a SOD-like anti-O2- mechanism.
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 microM 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.
Maczewski
M
M
Department of Clinical Physiology, Medical Center of Postgraduate Education, Warsaw, Poland. maczmich@cmkp.edu.pl
Duda
M
M
Pawlak
W
W
Beresewicz
A
A
D000818:Animals; D002374:Catalase / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019276:Glycocalyx / Q000378:metabolism; D006168:Guinea Pigs; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D020011:Protective Agents; D013481:Superoxides; D017665:Hydroxyl Radical; D002374:Catalase; D013482:Superoxide Dismutase; D003981:Diazoxide