Role of polyamines and cAMP-dependent mechanisms on 5alpha-dihydrotestosterone-elicited functional effects in isolated right atria of rat.
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 5alpha-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 degrees C and bubbled with carbogen. In male rats, the acute administration of 5alpha-dihydrotestosterone, a nonaromatizable derivate of testosterone, elicited a positive inotropism, which was associated with a negative chronotropism. As reported in the left atria, polyamines and beta-adrenoceptors played a role in 5alpha-dihydrotestosterone-elicited positive inotropism because the effect was antagonized by alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, and atenolol, a beta1-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 5alpha-dihydrotestosterone are not hormonally regulated because they are similarly produced in estrogenized females and gonadectomized male and female rats. These results suggest that the androgen could acutely improve cardiac performance.
Sánchez
Manuel
M
Farmacología, Departamento de Medicina, Universidad de Oviedo, Oviedo 33006, Spain. sanchezf@uniovi.es
Secades
Lorena
L
Bordallo
Carmen
C
Meana
Clara
C
Rubín
José Manuel
JM
Cantabrana
Begoña
B
Bordallo
Javier
J
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D016280:Atrial Function, Right / Q000187:drug effects*; D015317:Biogenic Polyamines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D000518:Eflornithine / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000728:Androgens; D015317:Biogenic Polyamines; D065108:Ornithine Decarboxylase Inhibitors; D011943:Receptors, Adrenergic, beta; D013196:Dihydrotestosterone; D001262:Atenolol; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase; D007545:Isoproterenol; D000518:Eflornithine