Role of Polyamines and cAMP-dependent Mechanisms on 5α-dihydrotestosterone-elicited Functional Effects in Isolated Right Atria of Rat

Abstract

Androgens produce acute vasodilation of systemic, pulmonary, and coronary arteries in several mammal preparations and increase cardiomyocyte contractility. A decrease of the spontaneous beating of sinoatrial cells has also been described. The aim of this study was to characterize the direct effect of 5a-dihydrotestosterone on the spontaneous chronotropism and inotropism in the same preparation as an approach to establish the effect on cardiac output and their mechanism of action. The effects were studied on isolated right atria of Wistar rats placed in an organ bath in Tyrode solution at 37 C and bubbled with carbogen. In male rats, the acute administration of 5a-dihydrotestosterone, a nonaromatizable derivate of testosterone, elicited a positive inotropism, which was associate with a negative chronotropism. As reported in the left atria, polyamines and b-adrenoceptors played a role in 5a-dihydrotestosterone–elicited positive inotropism because the effect was antagonized by a-difluoromethylornithine, an inhibitor of polyamine synthesis, and atenolol, a b1-adrenoceptor blocker, but not on the negative effect on chronotropism. The androgen increased the sinoatrial node recovery time, suggesting an effect on the mechanisms of spontaneous diastolic depolarization involved in atria pacemaking. These effects of 5a-dihydrotestosterone are not hormonally regulated because they are similarly produced in estrogenized females and gonadectomised male and female rats. These results suggest that the androgen could acutely improve cardiac performance.