In anesthetized pigs human chorionic gonadotropin increases myocardial perfusion and function through a ß-adrenergic-related pathway and nitric oxide.

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, dP/dtmax, segmental shortening, cardiac output and coronary NO release (P<0.0001). These hemodynamic responses were graded in a further 5 pigs. Moreover, while blockade of muscarinic cholinoceptors (n=5) and of a-adrenoceptors (n=5) did not abolish the observed responses, ß1-adrenoceptors blocker (n=5) prevented the effects of hCG on cardiac function. In addition, ß2-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 signalling and ERK1/2, Akt, p38MAPK involvement, which were activated as downstream effectors of ß2-adrenoceptors stimulation. In conclusion, in anesthetized pigs hCG primarily increased cardiac function and perfusion through the involvement of ß-adrenoceptors and NO release. Moreover, cAMP/PKA-dependent kinases phosphorylation was found to play a role in eliciting the observed NO production in CEC.