Evidence for the involvement of peroxynitrite in ischaemic preconditioning in rat isolated hearts

Abstract

1 The aim of this study was to investigate the involvement of peroxynitrite, reactive metabolite originating from nitric oxide and superoxide, in preconditioning of the ischaemic myocardium in rat isolated hearts. 2 Isolated hearts perfused with Krebs-Henseleit solution were preconditioned either by 3 min of coronary artery occlusion (CAO) or by peroxynitrite administration at three dierent concentrations (0.1, 1, 10 mM) for 3 min, followed by 10 min reperfusion and 30 min of CAO. Peroxynitrite, at 1 mM concentration, decreased the incidence of VT from 100% (n=14) to 62% (n=13) and abolished the occurrence of VF (50% in the control group). 3 N-2-mercaptopropionylglycine (MPG, 1 mM ± 10 mM) produced a concentration-dependent inhibition of peroxynitrite signals in luminol chemiluminescence and 67+1% inhibition was observed at 100 mM (n=7). MPG (at 300 mM, n=7) added to the perfusate 10 min prior to ischaemic preconditioning or peroxynitrite infusion and maintained until CAO, signi®cantly reversed the bene®cial eects of the ischaemic and peroxynitrite-treated groups. MPG administration in the peroxynitrite-treated group increased the incidence of VT from 62% (n=13) to 100% (n=10) and total VF from 0% (n=0) to 67% (n=10). Similarly, MPG elevated the incidence of VT from 50% (n=10) to 100% (n=8) in the ischaemic preconditioned group. On its own, MPG did not aect the severity of cardiac arrhythmias. 4 These results suggest that endogenously produced peroxynitrite plays a signi®cant role in the antiarrhythmic eect of ischaemic preconditioning in the rat isolated hearts.

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

“…Further studies also confirmed that enhanced peroxynitrite formation plays a central role in numerous cardiovascular diseases by inducing oxidative, nitrative and nitrosative stress (Pacher et al, 2007). However, peroxynitrite was demonstrated to have physiological functions (Lefer et al, 1997) and to play a role in triggering ischaemic preconditioning (Altug et al, 2000;Altup et al, 2001;Csonka et al, 2001). We have previously reported for the first time that peroxynitrite is a trigger of IPost since the peroxynitrite scavenger, FeTPPS, interfered with the cardioprotective effect of IPost (Kupai et al, 2009 Beginning of ischaemia a 10.7 ± 1.0 9.0 ± 0.8 11.5 ± 1.0…”

“…Increasing evidence suggests that enhanced formation of cardiac peroxynitrite is involved in cardioprotection afforded by both pre- (Altug et al, 2000;Altup et al, 2001;Csonka et al, 2001) and postconditioning (Kupai et al, 2009;Li et al, 2013). Kupai et al reported first that IPost failed to decrease infarct size in the presence of a peroxynitrite decomposition catalyst, thereby suggesting essential triggering role of peroxynitrite in postconditioninginduced cardioprotection (Kupai et al, 2009).…”

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

“…Therefore, low concentrations of peroxynitrite, such as those produced in LPS preconditioning, can be beneficial to the ischemic brain. In the peripheral circulation, peroxynitrite improves endothelial function, protects the myocardium from injury, and can act as a preconditioning agent Nossuli et al, 1997;Altug et al, 2000). In the CNS, peroxynitrite is involved in LPS preconditioning against excitotoxic brain lesions .…”

Potential Benefits of Peroxynitrite

“…These results suggest that PN, at low concentrations, may exert favorable effects in decreasing the incidence of ischemia/reperfusion-induced dysrhythmias [290]. Moreover, the use of a cell-permeant antioxidant that reacts rapidly with PN, abolished the beneficial effect of PN [296].…”