Post-ischemic reperfusion with diosmin attenuates myocardial injury through a nitric oxidase synthase-dependent mechanism

Diosmin is a citrus flavonoid with broad biological activities. Moreover, the administration of biologically active compounds during the myocardial reperfusion potentiates the cardioprotection and survival rate. Hence, this study aimed to evaluate whether the reperfusion with diosmin elicits protection to ischemic hearts and to investigate the mechanisms involved in these effects. Male Wistar rats were subjected to myocardial ischemia-reperfusion (I/R) injury in the presence or absence of diosmin (0.1 μM). When appropriated, a non-selective nitric oxide synthase (NOS) inhibitor was used. Here, we show that the severe impairment of contractile function induced by I/R was fully recovered by the administration of diosmin. Our results also showed that reperfusion with diosmin markedly reduced the incidence of cardiac arrhythmias and enhanced coronary microvascular function. Moreover, the rise of end-products of lipid peroxidation, biomarkers of cell damage, and infarct size were dramatically attenuated with diosmin reperfusion. However, all cardioprotective effects mediated by diosmin were fully abolished by inhibition of NOS, including the contractile function, arrhythmias index, coronary flow, and infarct size. Together, our data show that inclusion of diosmin during myocardial reperfusion potentiates the cardioprotection through a NOS-dependent mechanism. •Reperfusion of ischemic heart with diosmin attenuates ventricular dysfunction.•Diosmin reduces cardiac arrhythmias and coronary microvascular dysfunction.•The effects of diosmin occur through a nitric oxidase synthase-dependent mechanism.