Peroxynitrite triggers a delayed resistance of coronary endothelial cells against ischemia-reperfusion injury

Experiments were designed to test whether nitric oxide (NO) and peroxynitrite trigger delayed coronary endothelial protection induced by preconditioning (PC) in rats. Prolonged ischemia reperfusion markedly reduced the response of isolated coronary arteries to acetylcholine, and this was prevented by PC performed 24 h earlier. The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) administered during PC abolished its delayed endothelial protective effect, whereas the inducible NOS inhibitor N-(3(aminomethyl)benzyl)acetaminide had no effect. Delayed endothelial PC was also abolished by the peroxynitrite scavengers selenomethionine or uric acid given during PC. In parallel, the NO/peroxynitrite donor S-morpholinosydnonimine and authentic peroxynitrite, administered 24 h before prolonged ischemia-reperfusion mimicked endothelial PC, whereas the NO donor S-nitroso-N-acetylpencillamine had no effect. This suggests that peroxynitrite is an essential trigger of the delayed coronary endothelial protection induced by PC in rat hearts.