INFLUENCE OF HORMONAL STATUS IN RELAXANT EFFECT OF DIETHYLSTILBESTROLAND NIFEDIPINE ON ISOLATED RAT UTERUS CONTRACTION

1. The effects of diethylstilbestrol (DES, 10(-7)-10(-5) M) and nifedi pine (10(-10)-10(-7) M) on KCl (60 mM)-induced tonic contraction in th e 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 rela xation produced by nifedipine in ovariectomized rats (EC(50) = 5.59 +/ - 1.25 x 10(-9) M) is potentiated in uterus of rats treated with 17 be ta-estradiol and progesterone (EC(50) = 0.59 +/- 0.1 and 0.49 +/- 0.1 x 10(-9)M, respectively) but not in the 17 alpha-estradiol-treated rat s (3.01 +/- 0.6 x 10(-9) M). 3. The relaxation produced by DES on ovar iectomized rats (EC(50) = 0.84 +/- 0.14 x 10(-6) M) is reduced when th e rats are treated with 17 beta-estradiol (EC(50) = 2.22 +/- 0.2 x 10( -6)M) or progesterone (EC(50) = 1.24 +/- 0.08 x 10(-6) M), but unmodif ied by 17 alpha-estradiol (EC(50) = 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 counteracte d the relaxation of DES at 45.7% on ovariectomized rats but this was l ower than 30% in the other groups. 5. Our results suggest that in ovar iectomized rats the effects of both nifedipine and DES are similar, bu t 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). 6. The modifications produced by 17 alpha-estradiol are similar to those produced by the ovariectomy and t his suggests that 17 alpha-estradiol is a drug lacking estrogenic acti vity.