Influence of hormonal status in relaxant effect of diethylstilbestrol and nifedipine on isolated rat uterus contraction.
1. The effects of diethylstilbestrol (DES, 10(-7)-10(-5) M) and nifedipine (10(-10)-10(-7) M) on KCl (60 mM)-induced tonic contraction in the uterus of ovariectomized and 17 beta-estradiol (0.1 mg/kg/day, s.c.)-, 17 alpha-estradiol (0.1 mg/kg/day, s.c.)-, or progesterone (2 mg/kg/day, s.c.)-treated rats have been assayed. 2. The dose-dependent relaxation produced by nifedipine in ovariectomized rats (EC50 = 5.59 +/- 1.25 x 10(-9) M) is potentiated in uterus of rats treated with 17 beta-estradiol and progesterone (EC50 = 0.59 +/- 0.1 and 0.49 +/- 0.1 x 10(-9) M, respectively) but not in the 17 alpha-estradiol-treated rats (3.01 +/- 0.6 x 10(-9) M). 3. The relaxation produced by DES on ovariectomized rats (EC50 = 0.84 +/- 0.14 x 10(-6) M) is reduced when the rats are treated with 17 beta-estradiol (EC50 = 2.22 +/- 0.2 x 10(-6)M) or progesterone (EC50 = 1.24 +/- 0.08 x 10(-6) M), but unmodified by 17 alpha-estradiol (EC50 = 0.58 +/- 0.01 x 10(-6) M). 4. The nifedipine-induced relaxation is reversed with Bay K 8644 (10(-10)-10(-6) M) in all experimental conditions. However, Bay K 8644 counteracted the relaxation of DES at 45.7% on ovariectomized rats but this was lower than 30% in the other groups. 5. Our results suggest that in ovariectomized rats the effects of both nifedipine and DES are similar, but 17 beta-estradiol and progesterone produce a contrary effect on the relaxation induced by nifedipine and DES (by increasing the nifedipine and decreasing the DES effects).(ABSTRACT TRUNCATED AT 250 WORDS)
Fernández
A I
AI
Departamento de Medicina, Facultad de Medicina, Oveido, Spain.
García de Boto
M J
MJ
Gutiérrez
M
M
Cantabrana
B
B
Hidalgo
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006728:Hormones / Q000494:pharmacology; D009119:Muscle Contraction; D009543:Nifedipine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects*
D006728:Hormones; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004054:Diethylstilbestrol; D009543:Nifedipine