Chan W Y, Chen D L
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
Biol Reprod. 1992 Jan;46(1):58-64. doi: 10.1095/biolreprod46.1.58.
Parturition in rats is associated with an abrupt and marked increase in myometrial oxytocin (OT) receptor concentrations. In this study, we investigated the role of myometrial OT receptors in the initiation and the process of parturition. We produced chronic OT receptor blockade during the last 3 days of gestation by administration of a specific OT antagonist at 100 micrograms/day and 300 micrograms/day. We also suppressed OT receptor formation by inhibiting prostaglandin synthesis with naproxen sodium at 2 mg/day and 5 mg/day. We found that chronic blockade of OT receptors inhibited the uterotonic response to OT in Day 22 and Day 23 pregnant rats in a dose-dependent manner. OT antagonist treatment did not prolong the gestation period. However, the duration of parturition, fetal mortality, and the mortality incidence were increased in rats treated with the high dose of the OT antagonist compared to controls. Naproxen sodium at both dosage levels prolonged gestation by 24 h or longer, doubled the duration of parturition, and markedly increased fetal mortality and mortality incidence. Combined OT antagonist and naproxen treatment produced adverse outcomes similar to that produced by naproxen treatment alone. Myometrial OT receptor concentrations were markedly increased in all rats immediately postpartum, ranging from 210 to 425 fmol/mg protein compared to the 50 to 100 fmol/mg found in Day 21 and Day 22 pregnant rats. Correlation analyses between OT receptor concentrations and various parameters associated with gestation and parturition showed that there was a correlation between low OT receptor concentrations and long gestation period, prolonged parturition, and high fetal mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)
大鼠分娩与子宫肌层催产素(OT)受体浓度的突然显著增加有关。在本研究中,我们调查了子宫肌层OT受体在分娩启动和过程中的作用。在妊娠的最后3天,我们通过每天给予100微克和300微克的特定OT拮抗剂来产生慢性OT受体阻断。我们还通过每天给予2毫克和5毫克的萘普生钠抑制前列腺素合成来抑制OT受体的形成。我们发现,慢性阻断OT受体以剂量依赖的方式抑制了第22天和第23天妊娠大鼠对OT的子宫收缩反应。OT拮抗剂治疗并未延长妊娠期。然而,与对照组相比,高剂量OT拮抗剂治疗的大鼠分娩持续时间、胎儿死亡率和死亡发生率增加。两个剂量水平的萘普生钠均使妊娠期延长24小时或更长时间,使分娩持续时间加倍,并显著增加胎儿死亡率和死亡发生率。联合OT拮抗剂和萘普生治疗产生的不良后果与单独使用萘普生治疗相似。所有大鼠产后立即子宫肌层OT受体浓度显著增加,范围为210至425飞摩尔/毫克蛋白,而在第21天和第22天妊娠大鼠中为50至100飞摩尔/毫克。OT受体浓度与妊娠和分娩相关的各种参数之间的相关性分析表明,低OT受体浓度与妊娠期延长、分娩延长和高胎儿死亡率之间存在相关性。(摘要截短至250字)