The influence of oestrogen and progesterone on the actions of two calcium entry blockers in the rat uterus.
The potency and maximum effect of the calcium entry blocker nifedipine as an inhibitor of uterine contractions in vivo are increased in rats in late pregnant compared with non-pregnant rats. The influence of ovarian steroids produced during pregnancy (oestrogen and progesterone) on the potency and maximum effect of two calcium entry blockers (nifedipine and diltiazem) against uterine contractions during i.v. infusion was therefore investigated in anaesthetized non-pregnant rats. The influence of pregnancy on the relationship between serum concentrations of diltiazem during i.v. infusion and uterine and cardiovascular effects was also investigated. A twofold increase in the potency of nifedipine as an inhibitor of uterine contractions was observed in rats treated with oestrogen or oestrogen plus progesterone compared with rats treated with corn oil. There was no change in potency in rats receiving progesterone alone. Maximum inhibition of uterine contractions by nifedipine was significantly increased by all three hormone treatments. A twofold increase in the potency of diltiazem and a significant increase in maximum inhibition of uterine contractions was observed in rats in late pregnancy compared with non-pregnant rats. No increase in potency of diltiazem in reducing blood pressure or heart rate was observed in rats in late pregnancy. No significant difference in potency of diltiazem against uterine contractions was observed in rats treated with oestrogen, progesterone or oestrogen plus progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Downing
S J
SJ
Department of Physiological Sciences, University of Manchester.
Hollingsworth
M
M
Miller
M
M
D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009543:Nifedipine / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*
D011374:Progesterone; D004958:Estradiol; D004110:Diltiazem; D009543:Nifedipine