Peroxynitrite Reduces Myocardial Infarct Size and Preserves Coronary Endothelium After Ischemia and Reperfusion in Cats

Abstract

These data suggest that physiologically relevant concentrations of ONOO- exert significant cardioprotective and vasculoprotective effects in MI/R in cats, at least partially by attenuating PMN-endothelium interactions.

Potential Benefits of Peroxynitrite

“…The hindlimb vasodilator responses to PN were rapid in onset, short in duration, and the vasodilator responses to PN could be repeated without causing tachyphylaxis [210]. The absence of the development of tachyphylaxis to the vasodilator response to PN is in agreement with studies in the systemic and hindlimb vascular bed of the rat, and in isolated coronary arteries from the dog and cat [23,25,202]. Although PN has been reported to produce vascular dysfunction, the results of these studies observed that vascular responses of PN to could be repeated as subsequent injections, in doses up to 4000 nmol, had no significant effect on baseline perfusion pressure or on responses to vasoactive agonists [210].…”

“…These data suggest that PN does not impair endothelial function in the hindlimb vascular bed. The results showing that vasodilator responses to acetylcholine are not inhibited are consistent with results in the hindquarters vascular bed or in aortic rings of the rat, in isolated cat coronary arteries, and in isolated rat pulmonary arteries where responses to acetylcholine were enhanced by the highest dose of PN studied [25,105,125,202]. These data are in contrast to studies showing that responses to vasodilator agents, including acetylcholine, are reduced after the development of tachyphylaxis to PN [59,154].…”

“…These data are in contrast to studies showing that responses to vasodilator agents, including acetylcholine, are reduced after the development of tachyphylaxis to PN [59,154]. The explanation for differences in results is uncertain, but may be explained by the observation that in studies where responses to acetylcholine were preserved, tachyphylaxis to PN was not observed [25,105,125,202]. The repeated administration of PN did not alter vasoconstrictor responses to norepinephrine, U46619, or angiotensin II in the hindlimb vascular bed.…”

“…In studies in isolated rat pulmonary artery rings, in isolated rat aortic rings, in feline coronary artery rings, or in rat pulmonary and systemic circulations, vasorelaxant responses to acetylcholine were not inhibited following exposure to PN, and tachyphylaxis to the vasorelaxant response to PN was not reported, and in one preparation, responses to acetylcholine were enhanced [25,105,125]. However, responses in other vascular beds of the cat are not well described, that led this laboratory to investigate responses of PN in the hindlimb vascular bed of the cat [202,210].…”

“…In contrast, PN has been shown to have beneficial effects similar to those of NO and has been shown to produce vasorelaxation [20,21], inhibit platelet aggregation [22,23], and can limit ischemia-reproduction injury [24][25][26]. In this review, we describe the progress made in understanding the beneficial role of PN in the cardiovascular system.…”