Neuregulin-1 induces a negative inotropic effect in cardiac muscle - Role of nitric oxide synthase

Article

关键词: VENTRICULAR MYOCYTES;    ERBB2;    HEART;    HYPERTROPHY;    PERFORMANCE;    MECHANISMS;    INDUCTION;   

DOI  :  10.1161/01.CIR.0000114521.88547.5E

来源: SCIE

【 摘 要 】

Background - Deficient cardiac neuregulin/ErbB signaling increases susceptibility to heart failure. In this study, we examined the effects of neuregulin-1 (NRG-1) on myocardial contractility. Methods and Results - NRG-1 (alpha and beta isoforms) induced a negative inotropic effect in isolated rabbit papillary muscles and a rightward shift of the dose-response curve to isoproterenol. Both effects were attenuated by L-NMMA, which suggests a role for NO synthase. In cultured rat cardiomyocytes, NRG-1beta enhanced nitrite production and resulted in phosphorylation of endothelial NO synthase and the serine/threonine kinase Akt. Conclusions - NRG-1 has negative inotropic effects that are preserved during beta-adrenergic stimulation and activates endothelial NO synthase in cardiomyocytes.

【 授权许可】

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