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


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.
Lemmens
Katrien
K
Laboratory of Physiology, University of Antwerp, Groenenborgerlaan 171, Building V, 6th Floor, 2020 Antwerp, Belgium. gilles.dekeulenaer@ua.ac.be
Fransen
Paul
P
Sys
Stanislas U
SU
Brutsaert
Dirk L
DL
De Keulenaer
Gilles W
GW
D000818:Animals; D002478:Cells, Cultured; D046508:Culture Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology*; D020890:Neuregulin-1 / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt