Jing-Lin Zhao1, Yue-Jin Yang, Ji-Lin Chen, Lian-Ming Kang, Yuan Wu, Run-Lin Gao. 1. Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Li Shi Road 167, West City District, Beijing, 100037, China.
Abstract
INTRODUCTION: It has been found that nicorandil can attenuate myocardial no-reflow. However, the exact cause of this beneficial effect has remained unclear. We investigated whether the beneficial effect of nicorandil on myocardial no-reflow could be partly due to its protection against endothelial dysfunction. METHODS: Ligation area and area of no-reflow were determined echocardiographically and pathologically in sixty-two animals randomized into 7 study groups: 9 controls, 9 nicorandil-treated, 8 glibenclamide (K(ATP) channel blocker)-treated, 10 N(G)-monomethyl-L-arginine (L-NMMA, nonselective nitric oxide synthase antagonist)-treated, 10 nicorandil and glibenclamide-treated, 8 nicorandil and L-NMMA-treated and 8 sham-operated. The acute myocardial infarction and reperfusion model was created with one 3-h occlusion of the left anterior descending coronary artery followed by 2 h of reperfusion. Constitutive nitric oxide synthase (cNOS) activity and inducible nitric oxide synthase (iNOS) activity were also quantified. RESULTS: Compared with the control group, nicorandil significantly improved ventricular function, increased coronary blood flow volume (P<0.01), decreased area of no-reflow and reduced necrosis area. Nicorandil also increased the cNOS activity and decreased iNOS activity (P<0.05). L-NMMA and glibenclamide abrogated the effects of nicorandil on ventricular function, coronary blood flow volume, area of no-reflow, necrosis area and cNOS activity, but not iNOS activity. CONCLUSIONS: The beneficial effect of nicorandil on myocardial no-reflow could be due to its protection of endothelial function via the activation of K(ATP) channel.
INTRODUCTION: It has been found that nicorandil can attenuate myocardial no-reflow. However, the exact cause of this beneficial effect has remained unclear. We investigated whether the beneficial effect of nicorandil on myocardial no-reflow could be partly due to its protection against endothelial dysfunction. METHODS: Ligation area and area of no-reflow were determined echocardiographically and pathologically in sixty-two animals randomized into 7 study groups: 9 controls, 9 nicorandil-treated, 8 glibenclamide (K(ATP) channel blocker)-treated, 10 N(G)-monomethyl-L-arginine (L-NMMA, nonselective nitric oxide synthase antagonist)-treated, 10 nicorandil and glibenclamide-treated, 8 nicorandil and L-NMMA-treated and 8 sham-operated. The acute myocardial infarction and reperfusion model was created with one 3-h occlusion of the left anterior descending coronary artery followed by 2 h of reperfusion. Constitutive nitric oxide synthase (cNOS) activity and inducible nitric oxide synthase (iNOS) activity were also quantified. RESULTS: Compared with the control group, nicorandil significantly improved ventricular function, increased coronary blood flow volume (P<0.01), decreased area of no-reflow and reduced necrosis area. Nicorandil also increased the cNOS activity and decreased iNOS activity (P<0.05). L-NMMA and glibenclamide abrogated the effects of nicorandil on ventricular function, coronary blood flow volume, area of no-reflow, necrosis area and cNOS activity, but not iNOS activity. CONCLUSIONS: The beneficial effect of nicorandil on myocardial no-reflow could be due to its protection of endothelial function via the activation of K(ATP) channel.