Figure 1.

The detrimental effect of iNOS/NO on ischemia reperfusion injury. In response to myocardial ischemia, the upregulated iNOS-derived NO enhanced the level of intracellular cGMP, resulting in a decrease in Ca²⁺ influx, which depresses myofilament sensitivity to Ca²⁺ and subsequently attenuates cardiac contractile function. High levels of iNOS-derived NO also contribute to the formation of peroxynitrite, which subsequently leads to significantly increased oxidative stress and severe myocardial apoptosis. Together with iNOS/NO-mediated proinflammatory responses, these multiple actions of iNOS/NO exacerbate myocardial ischemia reperfusion injury.