Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia‐reperfusion injury and preconditioning

Abstract

There appears to be a controversy in the study of myocardial ischaemia-reperfusion injury and preconditioning whether nitric oxide (NO) plays a protective or detrimental role. A number of ®ndings and the interpretation of the results to date do not support such a controversy. An understanding of the latest developments in NO, superoxide (O 2 7´) and peroxynitrite (ONOO 7 ) biology, as well as the various ischaemic animal models utilized is necessary to resolve the apparent controversy. NO is an important cardioprotective molecule via its vasodilator, antioxidant, antiplatelet, and antineutrophil actions and it is essential for normal heart function. However, NO is detrimental if it combines with O 2 7´t o form ONOO 7 which rapidly decomposes to highly reactive oxidant species. There is a critical balance between cellular concentrations of NO, O 2 7´, and superoxide dismutase which physiologically favour NO production but in pathological conditions such as ischaemia and reperfusion result in ONOO 7 formation. In contrast, exposure of the heart to brief episode(s) of ischaemia markedly enhances its ability to withstand a subsequent ischaemic injury. The triggering of this endogenous cardioprotective mechanism known as preconditioning requires both NO and O 2 7´s ynthesis. However, preconditioning in turn attenuates the overproduction of NO, O 2 7´a nd ONOO 7 during a subsequent episode of ischaemia and reperfusion, thereby protecting the heart. Here we review the roles of NO, O 2 7´, and ONOO 7 in both ischaemia-reperfusion injury and preconditioning.

Wine polyphenols induce hypotension, and decrease cardiac reactivity and infarct size in rats: involvement of nitric oxide

“…It is well documented that NO has protective effects against global ischaemia-reperfusion injury (Ferdinandy & Schulz, 2003). In accordance with the literature, RWPC treatment induced an increase in nitrite concentration in cardiac effluent (which is an index of NO production even though a direct measurement of NO using electronic paramagnetic resonance technique would be more appropriate), which was sensitive to concomitant administration of L-NAME.…”

Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation

“…This redox-mechanism includes an increase in NO • and derivative production [9,15,20,34,49,56] that increases the amount of protein SNO, which is also maintained by reduced nitrosylation breakdown by SOD downregulation (as hypothesized, Fig. 1).…”

“…A pivotal cardioprotective role for NO • from enzymatic and non-enzymatic origin has been shown for both pre and postconditioning [13,15,25,26,[46][47][48][49][50]60,66,69]. In fact, NO • is a cardiovascular protective molecule via multiple effects, both in normoxia and particularly during reperfusion [15,50,66].…”

“…In fact, NO • is a cardiovascular protective molecule via multiple effects, both in normoxia and particularly during reperfusion [15,50,66]. Accordingly, in preconditioning a central role is played by protein SNO, which provides protection preventing further cellular oxidative and nitrosative stress in reperfusion [24,40,56].…”

“…Yet, the high reduction potential of NO • severely limits the formation of peroxynitrite (ONOO -) in this context [46,60,66]. Actually, ONOO -has also been proposed to be cardioprotective at very low concentrations [15,32,65,69] [59,60,66]. This secondary reaction may be responsible of both ONOO -and 3-NT level lowering, and SNO augmentation (Fig.…”