Preconditioning decreases ischemia/reperfusion-induced peroxynitrite formation.
The role for peroxynitrite (ONOO(-)) in the mechanism of preconditioning is not known. Therefore, we studied effects of preconditioning and subsequent ischemia/reperfusion on myocardial ONOO(-) formation in isolated rat hearts. Hearts were subjected to a preconditioning protocol (three intermittent periods of global ischemia/reperfusion of 5 min duration each) followed by a test ischemia/reperfusion (30 min global ischemia and 15 min reperfusion). When compared to nonpreconditioned controls, preceding preconditioning improved postischemic cardiac performance and significantly decreased test ischemia/reperfusion-induced formation of free nitrotyrosine measured in the perfusate as a marker for cardiac endogenous ONOO(-) formation. During preconditioning, however, the first period of ischemia/reperfusion increased nitrotyrosine formation, which was attenuated after the third period of ischemia/reperfusion. We conclude that classic preconditioning inhibits ischemia/reperfusion-induced cardiac formation of ONOO(-) and that subsequent periods of ischemia/reperfusion result in a gradual attenuation of ischemia/reperfusion-induced ONOO(-) generation. This mechanism might be involved in ischemic adaptation of the heart.
Csonka
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C
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary.
Csont
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T
Onody
A
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Ferdinandy
P
P
D000818:Animals; D001011:Aorta; D001783:Blood Flow Velocity; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D016277:Ventricular Function, Left
D009566:Nitrates; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase