Preconditioning decreases ischemia/reperfusion-induced peroxynitrite formation

The role for peroxynitrite (ONOO-) in the mechanism of preconditioning is n ot known. Therefore, we studied effects of preconditioning and subsequent i schemia/reperfusion on myocardial ONOO- formation in isolated rat hearts. H earts were subjected to a preconditioning protocol (three intermittent peri ods of global ischemia/reperfusion of 5 min duration each) followed by a te st ischemia/reperfusion (30 min global ischemia and 15 min reperfusion). Wh en compared to nonpreconditioned controls, preceding preconditioning improv ed postischemic cardiac performance and significantly decreased test ischem ia/reperfusion-induced formation of free nitrotyrosine measured in the perf usate as a marker for cardiac endogenous ONOO- formation. During preconditi oning, however, the first period of ischemia/reperfusion increased nitrotyr osine formation, which was attenuated after the third period of ischemia/re perfusion. We conclude that classic preconditioning inhibits ischemia/reper fusion-induced cardiac formation of ONOO- and that subsequent periods of is chemia/reperfusion result in a gradual attenuation of ischemia/reperfusion- induced ONOO- generation. This mechanism might be involved in ischemic adap tation of the heart. (C) 2001 Academic Press.