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.
Laude
Karine
K
Institut National de la Santé et de la Recherche Médicale E9920, Rouen University Medical School, France.
Thuillez
Christian
C
Richard
Vincent
V
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008715:Methionine / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012645:Selenomethionine / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D030421:Peroxynitrous Acid; D014527:Uric Acid; D009569:Nitric Oxide; C002385:linsidomine; D012645:Selenomethionine; D008715:Methionine; D008981:Molsidomine; D010396:Penicillamine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester