Peroxynitrite, the product of nitric oxide and superoxide, causes myocardial injury in the isolated perfused rat heart

Background Recent studies have determined that the product of( ).NO and superoxide is peroxynitrite (ONOO-), an anion with deleterious tissue-oxidant effects. Objective To examine the effects of ONOO- on the isolated perfused rat heart, Sprague-Dawley rat hearts were perfused with a cell-free, Krebs-Henseleit solution on a Langendorf perfusion apparatus. The hearts were subjected to 30 min infusions of vehicle (control); 10 mu mol/l S-nitroso-N-acetylpenicillamine (SNAP), an NO donor; 10 mu mol/l pyrogallol, a superoxide generator); 10 mu mol/l SNAP plus 10 mu mol/l pyrogallol, a mixture that generates peroxynitrite; or 10 mu mol/l SNAP plus 10 mu mol/l pyrogallol plus 300 U/ml superoxide dismutase, Results SNAP or pyrogallol alone had no effect on cardiac function at the concentration used; however, infusion of the combination of SNAP and pyrogallol resulted in significant decreases in left ventricular developed pressure (to 83 +/- 4%, P< 0.01, versus vehicle) and dp/dt(max) (to 76 +/- 6.2%, P< 0.01, versus vehicle), and also resulted in a significant increase in production of lactic dehydrogenase (to 118 +/- 4%, P< 0.01, versus vehicle). The administration of superoxide dismutase with SNAP and pyrogallol reversed these deleterious effects, Conclusion These results suggest that the formation of peroxynitrite significantly enhances the toxicities of (NO)-N-. and O-2(.-) and causes marked cardiac injury.