Neuregulin-1 induces a negative inotropic effect in cardiac muscle: role of nitric oxide synthase.

Lemmens, Katrien; Fransen, Paul; Sys, Stanislas U; Brutsaert, Dirk L; De Keulenaer, Gilles W · Circulation · 2004

basic_science · Level V

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Abstract

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. 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. NRG-1 has negative inotropic effects that are preserved during beta-adrenergic stimulation and activates endothelial NO synthase in cardiomyocytes.

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