Neuregulin-1 Induces a Negative Inotropic Effect in Cardiac Muscle: Role of Nitric Oxide Synthase

Overview

Journal Circulation

Specialty Cardiology & Vascular Diseases

Date 2004 Jan 21

PMID 14732742

Citations 46

Authors

Katrien Lemmens

Paul Fransen

Stanislas U Sys

Dirk L Brutsaert

Gilles W De Keulenaer

Affiliations

Soon will be listed here.

Abstract

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.

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