奈比洛尔抑制心衰和非心衰心肌细胞中一氧化氮合酶活性的作用研究

Nebivolol in the Inhibition of eNOS Activity in Cadiocytes with or without Heart Failure

目的:研究奈比洛尔在心衰和非心衰的心肌细胞中对一氧化氮合酶(eNOS)活性的影响。方法:采用免疫组化的方法测定应用奈比洛尔、卡维地洛和美托洛尔等药物后人、鼠心室心肌细胞中eNOS蛋白水平移位及eNOSser1177磷酸化结果。结果:与未加药物的对照组比较,应用奈比洛尔后,非心衰受试者的心室心肌细胞中的eNOS移位及eNOSSer1177磷酸化未见明显差异(P>0.1) ;与用药前比较,2种指标在非心衰大鼠心肌细胞中用药后也未见明显差异(P>0.1) ,但在心衰受试者的左室心肌细胞中,可见2种指标明显受抑(P≤0.05)。卡维地洛、美托洛尔在所有心肌组织中均不影响eNOS活性。结论:奈比洛尔不影响非心衰的左室心肌细胞eNOS活性,但可抑制心衰细胞eNOS活性,由此发挥其不同的有益的临床作用。

OBJECTIVE： To investigate the effects of the nebivolol on nitricoxide synthase （eNOS） activity in cardiac myocytes with or without heart failure. METHODS： eNOS translocation in ventricular cardiac myocytes and the phosphorylation of eNOS^ser117 in human and mice were measured by immunohistochemical staining after administration of nebivolol, carvedilol and metoprolol etc. RESULTS： As compared with control group （in which no drug was administered）, no significant differences were noted in eNOS- translocation and phosphorylation of eNOS^ser117 in cardiac myocytes of subjects without heart failure after administration of nebivolol（P 〉 0.1） . As compared with before medication, no significant differences were noted in eNOS - translocation and phosphorylation of eNOS^ser117 in cardiac myocytes of rats without heart failure after medication（P 〉0.1）, but which were inhibited significantly in the left ventricular cardiac myocytes of the subjects with heart fail- ure（P≤0.05） . Both carvedilol and metoprolol exhibited no effect on eNOS activity in all the investigated cardiac myocytes. CONCLUSIONS： Nebivolol does no effect on eNOS activity of left ventricular cadiocytes in subjects or rats without hear failure but it can inhibit eNOS activity of cadiocytes in subjects or rats with heart failure so as to exert its beneficial clinical effect.