The interaction of nitric oxide synthase and extracellular signal regulated kinase in cardioprotection of 11,12-epoxyeicosatrienoic acid

Objective To observe the effects of extracellular signal regulated kinase(ERK)1/2 inhibitor on the change of structural nitric oxide synthase(sNOS) caused by the 11,12-epoxyeicosatrienoic acid(1,2-EET) and study the mode of action of NOS and ERK in cardioprotection of 11,12-EET. Methods Myocardial ischemic/reperfusion model was produced by ligating the left anterior descending coronary artery for 60 min followed by 30 min reperfusion.The rats were divided into 4 groups: ischemia/reperfusion group(I/R);Sham group(Sham);EET and ischemia/reperfusion group(EET+I/R);EET,ischemia/reperfusion and PD098059 group(EET+I/R+PD).The heart function was evaluated by observing the maximum changes of intraventricular pressure(+dp/dt max and-dp/dt max).The activities of nitric oxide synthase of myocardium were examined by colorimetric method. Results At 30 min reperfusion,+dp/dt max and-dp/dt max decreased significantly in I/R group compared with Sham group and EET+IR group(P0.01),and those in EET+I/R+PD group were less than those in EET+I/Rgroup(P0.01).The activities of sNOS in IR group were lower than those in Sham group and EET+I/R group(P0.01),and those in EET+I/R group were higher than those in EET+I/R+PD group(P0.01). Conclusion Cardioprotective effect of 11,12-EET may be mediated by increasing the ERK then increasing the activity of sNOS.