孕酮对大鼠心房利钠因子的宫缩抑制活性的抑制作用以及孕酮受体拮抗剂RU486对其的增强作用。

Inhibition of the tocolytic activity of atrial natriuretic factor by progesterone and potentiation by progesterone receptor antagonist RU486 in rats.

Potvin W, Mulay S, Varma D R

Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.

Br J Pharmacol. 1991 Oct;104(2):379-84. doi: 10.1111/j.1476-5381.1991.tb12439.x.

Abstract

The influence of progesterone on the activity of atrial natriuretic factor (ANF) on rat myometrial motor activity was determined in vitro. 2. ANF inhibited the tension development by myometrium from cycling or oestrogen-treated rats in a dose-dependent manner; maximal inhibition was 100%. 3. Injections of progesterone into rats inhibited the tocolytic activity of ANF in a dose and time-dependent manner. The tocolytic effects of ANF were completely abolished by 3 daily injections of 1 mg kg-1 progesterone. 4. Pregnancy-related increase in plasma progesterone was accompanied by a corresponding decrease in the tocolytic effects of ANF; myometria from gestational day 10 to 21 were completely refractory and those from earlier gestational age and immediate postpartum were responsive to ANF to varying degrees. 5. Treatment of pregnant rats with the progesterone antagonist, RU486, caused abortions and vaginal bleeding, decreased plasma progesterone concentrations and restored the tocolytic activity of ANF. Tocolytic activity of ANF on virgin rat myometria was potentiated by RU486. 6. Progesterone also inhibited the effects of ANF on myometria from ovariectomized rats. 7. Tocolytic activity of isoprenaline was not modified by progesterone, pregnancy, RU486 or ovariectomy. 8. It is concluded that progesterone antagonizes myometrial effects of ANF by an oestrogen-independent mechanism and the pregnancy-induced refractoriness to the tocolytic effects of ANF is caused by progesterone.

摘要

在体外测定了孕酮对大鼠子宫肌层运动活性中心房利钠因子（ANF）活性的影响。2. ANF以剂量依赖性方式抑制来自处于发情周期或经雌激素处理的大鼠子宫肌层的张力发展；最大抑制率为100%。3. 给大鼠注射孕酮以剂量和时间依赖性方式抑制ANF的安胎活性。连续3天每天注射1 mg kg-1孕酮可完全消除ANF的安胎作用。4. 与妊娠相关的血浆孕酮升高伴随着ANF安胎作用相应降低；妊娠第10至21天的子宫肌层对ANF完全无反应，而妊娠早期和产后即刻的子宫肌层对ANF有不同程度的反应。5. 用孕酮拮抗剂RU486处理妊娠大鼠会导致流产和阴道出血，降低血浆孕酮浓度并恢复ANF的安胎活性。RU486增强了ANF对未孕大鼠子宫肌层的安胎活性。6. 孕酮也抑制ANF对去卵巢大鼠子宫肌层的作用。7. 异丙肾上腺素的安胎活性不受孕酮、妊娠、RU486或去卵巢的影响。8. 得出结论：孕酮通过一种不依赖雌激素的机制拮抗ANF对子宫肌层的作用，妊娠诱导的对ANF安胎作用的不应性是由孕酮引起的。