Effects of epidermal growth factor on epinephrine-stimulated heart function in rodents.
Epidermal growth factor (EGF) interferes with beta-adrenergic receptor (beta-AR) signaling in adipocytes and hepatocytes, which leads to decreased lipolytic and glycogenolytic responses, respectively. We studied the effect of EGF on the heart. EGF interfered with the cAMP signal generated by beta-AR agonists in cardiac myocytes. In perfused hearts, EGF decreased inotropic and chronotropic responses to epinephrine but not to 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate. Sustained epinephrine infusion induced heart contracture, which resulted in altered heart function as demonstrated by decreased inotropy and increased heart rate variability. EGF prevented all these alterations. In the whole animal (anesthetized mice), EGF administration reduced the rise in heart rate induced by a single epinephrine dose and the occurrence of Bezold-Jarisch reflex episodes induced by repeated doses. Sialoadenectomy enhanced the response to epinephrine, and EGF administration restored normal response. All these results suggest that, by interfering with beta-AR signaling, EGF protects the heart against the harmful effects of epinephrine.
Lorita
Jordi
J
Department of Biochemistry and Molecular Biology, University of Barcelona, Avda. Diagonal 645, 08028 Barcelona, Spain.
Escalona
Noèlia
N
Faraudo
Susanna
S
Soley
Maria
M
Ramírez
Ignasi
I
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000322:Adrenergic Agonists; D011943:Receptors, Adrenergic, beta; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D004837:Epinephrine