title: In anesthetized pigs human chorionic gonadotropin increases myocardial perfusion and function through a β-adrenergic-related pathway and nitric oxide.
abstract: Human chorionic gonadotropin (hCG) is not only responsible for numerous pregnancy-related processes, but can affect the cardiovascular system as well. So far, however, information about any direct effect elicited by hCG on cardiac function, perfusion, and the mechanisms involved has remained scarce. Therefore, the present study aimed to determine the primary in vivo effect of hCG on cardiac contractility and coronary blood flow and the involvement of autonomic nervous system and nitric oxide (NO). Moreover, in coronary endothelial cells (CEC), the intracellular pathways involved in the effects of hCG on NO release were also examined. In 25 anesthetized pigs, intracoronary 500 mU/ml hCG infusion at constant heart rate and aortic blood pressure increased coronary blood flow, maximum rate of change of left ventricular systolic pressure, segmental shortening, cardiac output, and coronary NO release (P < 0.0001). These hemodynamic responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoceptors (n = 5) and of α-adrenoceptors (n = 5) did not abolish the observed responses, β1-adrenoceptors blocker (n = 5) prevented the effects of hCG on cardiac function. In addition, β2-adrenoceptors (n = 5) and NO synthase inhibition (n = 5) abolished the coronary response and the effect of hCG on NO release. In CEC, hCG induced the phosphorylation of endothelial NO synthase through cAMP/PKA signaling and ERK1/2, Akt, p38 MAPK involvement, which were activated as downstream effectors of β2-adrenoceptor stimulation. In conclusion, in anesthetized pigs, hCG primarily increased cardiac function and perfusion through the involvement of β-adrenoceptors and NO release. Moreover, cAMP/PKA-dependent kinases phosphorylation was found to play a role in eliciting the observed NO production in CEC.
authors.affiliation: Physiology Laboratory, Department of Translational Medicine, University East Piedmont A. Avogadro, Novara, Italy. grossini@med.unipmn.it
authors.forename: Elena
authors.initials: E
authors.lastname: Grossini
authors.forename: Daniela
authors.initials: D
authors.lastname: Surico
authors.forename: David A S G
authors.initials: DA
authors.lastname: Mary
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.forename: Nicola
authors.initials: N
authors.lastname: Surico
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013552:Swine; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D018343:Receptors, Adrenergic, beta-2; D009569:Nitric Oxide; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: adrenergic receptors; cardiac function; cardiac perfusion; gonadotropins; nitric oxide