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 mumol/l S-nitroso-N-acetylpenicillamine (SNAP), an NO donor; 10 mumol/l pyrogallol, a superoxide generator); 10 mumol/l SNAP plus 10 mumol/l pyrogallol, a mixture that generates peroxynitrite; or 10 mumol/l SNAP plus 10 mumol/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/dtmax (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 and O2.- and causes marked cardiac injury.
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 mumol/l S-nitroso-N-acetylpenicillamine (SNAP), an NO donor; 10 mumol/l pyrogallol, a superoxide generator); 10 mumol/l SNAP plus 10 mumol/l pyrogallol, a mixture that generates peroxynitrite; or 10 mumol/l SNAP plus 10 mumol/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/dtmax (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 and O2.- and causes marked cardiac injury.
Authors: Mark J Kohr; Honglan Wang; Debra G Wheeler; Murugesan Velayutham; Jay L Zweier; Mark T Ziolo Journal: Free Radic Biol Med Date: 2008-04-04 Impact factor: 7.376
Authors: N Paolocci; W F Saavedra; K M Miranda; C Martignani; T Isoda; J M Hare; M G Espey; J M Fukuto; M Feelisch; D A Wink; D A Kass Journal: Proc Natl Acad Sci U S A Date: 2001-08-21 Impact factor: 11.205
Authors: Mark J Kohr; Honglan Wang; Debra G Wheeler; Murugesan Velayutham; Jay L Zweier; Mark T Ziolo Journal: Cardiovasc Res Date: 2007-09-19 Impact factor: 10.787