Effects of androgens and antiandrogens on the inotropism induced by ouabain and isoproterenol on the left atrium of the rat in vitro.
1. The effect of androgens 5 beta- and 5 alpha-dihydrotestosterone (DHT, 10(-9) M), and the antiandrogens cyproterone acetate (CPA, 10(-8)-10(-6) M), chlormadinone acetate (CMA, 10(-8)-10(-6) M), medroxyprogesterone acetate (MPA, 10(-8)-10(-6) M), spironolactone (SPI, 10(-5) M), flutamide (F, 10(-5) M) and cimetidine (C, 10(-5) M), on inotropic positive effect induced by ouabain (10(-8)-10(-5) M) and isoproterenol (10(-8)-10(-6) M), on electrically stimulated left atria of rat, has been assayed. 2. Ouabain (10(-6) M) did not modify the inotropic effect of isoproterenol (10(-8)-10(-6) M). 3. The androgens 5 beta- and 5 alpha-DHT (10(-9) M) and the antiandrogens SPI (10(-6) M), F (10(-5) M) and C (10(-5) M) inhibit the inotropic effect of ouabain and isoproterenol on electrically stimulated left atria of the rat. 4. The antiandrogens CPA, MPA and CMA to 10(-7) M, inhibit the inotropic effect of ouabain. The CPA (10(-8)-10(-6) M) inhibit, in a dose-dependent way the positive inotropic effect of isoproterenol. MPA and CMA (10(-8)-10(-6) M) also inhibit the inotropic effect isoproterenol but the inhibitory effect is greater with 10(-8) M than 10(-6) M of both drugs. 5. Taken together, our results suggest that steroidal hormones could modulate the cardiac contractility through interference with Na-pump in a non-digitalic site and/or with intracellular mediators in left atrium.
García Valencia
V
V
Departamento de Medicina, Facultad de Medicina, Oviedo, Spain.
Gutierrez
M
M
Cantabrana
B
B
Hidalgo
A
A
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects*; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D000726:Androgen Antagonists; D000728:Androgens; D010042:Ouabain; D007545:Isoproterenol