Role of nitric oxide and oxidative stress in ischaemic myocardial injury and preconditioning

Nitric oxide (NO) plays an important role in the physiologic modulation of coronary artery tone and myocardial function. However, increased formation of NO within the myocardium can also have detrimental effects, contributing to the pathophysiology of myocardial dysfunction in ischaemic heart diseases. The role of reactive nitrogen species in the pathogenesis of myocardial dysfunction after ischaemia has been investigated in numerous studies. They reveal divergent and opposed effects of nitric oxide: from a cardioprotective action leading to ischaemic preconditioning after short ischaemic periods to a card iodepressive action after severe ischaemia/reperfus ion injury and heart failure. This review describes the determining role of reactive oxygen species on these opposite myocardial effects of NO. The final action of NO, whether cardioprotective or card iodepressive, strongly depends on the level of oxidative stress in the myocardium. Nitric oxide disrupts free radical and oxidant-mediated reactions, due to a strong attraction and interaction with superoxide. The level of oxidative stress is positively related to the severity of the ischaemic injury, making the results in different myocardial syndromes more concordant. If the increased production of NO is well in balance with a moderate increase in oxygen radicals, then NO will exert beneficial effects. However, if the oxygen radicals are produced in excess of NO as in prolonged ischaemic injury, then deleterious effects will be induced. Consequently, the balance between NO and free oxygen radicals is crucial in modulating the outcome after an ischaemic insult.