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

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-01, Vol.109 (3), p.324-326
• Main Authors: LEMMENS, Katrien, FRANSEN, Paul, SYS, Stanislas U, BRUTSAERT, Dirk L, DE KEULENAER, Gilles W
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cells, Cultured; Culture Techniques; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Medical sciences; Myocardial Contraction - drug effects; Myocardium - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - enzymology; Neuregulin-1 - pharmacology; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase - physiology; Nitric Oxide Synthase Type III; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rabbits; Rats; Rats, Sprague-Dawley
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000114521.88547.5E

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.