Effects of steroidal and non-steroidal antiandrogens on the left atrium of the rat in vitro.
1. The effect of steroidal-cyproterone acetate (CPA, 10(-7)-10(-5) M), clormadinone acetate (CMA, 10(-7)-10(-5) M), medroxyprogesterone acetate (MPA, 10(-7)-10(-5) M) and spironolactone (SPI, 10(-7)10(-5)M) and non-steroidal-flutamide (F, 10(-7)-6 x 10(-5) M) and cimetidine (C, 10(-7)-10(-4)M) antiandrogens on contractile force of electrically stimulated left atria of the rat have been assayed. 2. CPA, CMA, MPA and F inhibit, in a dose-dependent way, the contractile force of left atria. SPI enhanced (P less than 0.01 at 10(-6) M), and cimetidine did not modify the contractile force. 3. F, but not CPA, CMA, MPA or SPI, inhibit the contractile force induced by CaCl2 (0.9-7.2 mM) on electrically stimulated left atria. 4. The inhibitory effect of CPA (10(-7)-10(-5) M) was significantly increased by atropine (10(-6) M) and diltiazen (10(-5) M), and significantly reduced by yohimbine (10(-7) M) and in reserpinized (2.5 mg/kg, 48 and 24 hr before experiments) rats. 5. Our results suggest that the negative inotropism of steroidal antiandrogens could be related to inhibition of noradrenaline release, presumably through an alpha 2 adrenergic effect. The negative inotropism produced by F is related to inhibition of calcium dependent process on left atria contraction.
Garcia Valencia
V
V
Departamento de Medicina, Facultad de Medicina, Universidad de Oviedo, Spain.
Sanchez
M
M
Gutierrez
M
M
Cantabrana
B
B
Hidalgo
A
A
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002715:Chlormadinone Acetate / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003534:Cyproterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008525:Medroxyprogesterone / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology; D013256:Steroids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000726:Androgen Antagonists; D013256:Steroids; D002715:Chlormadinone Acetate; D013148:Spironolactone; D005485:Flutamide; D002927:Cimetidine; D003534:Cyproterone; D008525:Medroxyprogesterone; D002118:Calcium