Interaction of androgens with cardiotonic drugs in isolated left atrium of rat.
Pharmacological concentrations of androgens are known to elicit a rapid positive inotropism in isolated left atrium of male rats. Upon short-term exposure to androgens, an increase in intracellular cAMP levels has been observed, though delayed with respect to the time course of contraction, suggesting that other mechanisms may participate in initiating the contraction. Therefore, the interaction of positive inotropism elicited by ouabain, an inhibitor of Na(+)-K(+)-ATPase, and androgens was studied in isolated left atrium of rat. Androgens antagonized ouabain-elicited positive inotropism and increased the basal tone. Vanadate, an inhibitor of the Ca(2+) pump, produced a similar effect as androgens on ouabain-elicited positive inotropism. Therefore, androgens might interact with the Ca(2+) pump and this may explain the increase in basal tone. The conjugation of 5 alpha-dihydrotestosterone with bovine serum albumin produced the same effect, suggesting an extracellular interaction of androgens inhibiting the Na(+)-K(+)-ATPase that could increase intracellular Ca(2+) via the Na(+)-Ca(2+) exchange.
Secades
Lorena
L
Farmacología, Departamento de Medicina, Facultad de Medicina, Oviedo, Spain.
Cortina
Rosario
R
Velasco
Lucía
L
Bordallo
Javier
J
Hidalgo
Agustín
A
Sánchez
Manuel
M
D000584:Amiloride / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D006325:Heart Atria / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013030:Spain; D013329:Structure-Activity Relationship; D014638:Vanadates / Q000494:pharmacology
D000728:Androgens; D002316:Cardiotonic Agents; D013196:Dihydrotestosterone; D012710:Serum Albumin, Bovine; D014638:Vanadates; D010042:Ouabain; D000584:Amiloride