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容量在大鼠孕期抗利尿激素分泌调节中的作用

Role of volume in the regulation of vasopressin secretion during pregnancy in the rat.

作者信息

Barron W M, Stamoutsos B A, Lindheimer M D

出版信息

J Clin Invest. 1984 Apr;73(4):923-32. doi: 10.1172/JCI111316.

Abstract

We previously observed that osmoregulation and the osmotic threshold for antidiuretic hormone secretion were altered during pregnancy in Sprague-Dawley rats and the present study evaluated the influence of volume on arginine vasopressin (AVP) release during gestation in this species. Basal plasma osmolality (Posm) and intravascular volume were 297 +/- 3 mosmol/kg and 16.2 +/- 1.2 ml in virgin animals compared with 290 +/- 2 mosmol/kg and 20.2 +/- 2.3 ml in 14-d pregnant rats and 287 +/- 3 mosmol/kg and 25.2 +/- 2.3 ml in 21-d (near-term) pregnant rats (P less than 0.001, each pregnant group vs. virgin). Isosmotic volume depletion was produced by intraperitoneal polyethylene glycol. Volume decreased from 1 to 26% and blood pressure remained stable during decrements as high as 16%. Plasma AVP (PAVP) did not rise significantly in either group of pregnant animals or virgin controls until blood volume depletion reached 6-7%, after which levels rose in a similar exponential manner in virgin, 14-d, and 21-d pregnant animals. In terms of absolute changes, however, PAVP in gravid rats started to increase when intravascular volume was still considerably greater than basal blood volume in the nonpregnant controls. Other experiments, where Posm was increased by intraperitoneal hypertonic saline, reconfirmed that the osmotic threshold for AVP secretion was reduced congruent to 10 mosmol/kg during pregnancy and that AVP release was stimulated by increments in body tonicity as small as 1-2%. In parallel studies, blood volume contraction and increases in Posm were evoked by intraperitoneal polyethylene glycol dissolved in hypertonic saline and results compared with animals receiving intraperitoneal saline alone. Decrements in volume (congruent to 7%), which alone would increase PAVP minimally, increased the sensitivity of the secretory response to changes in osmolality two- to three-fold, an effect which was similar in virgin and gravid animals. Finally, restricting water intake of pregnant rats to that of virgins on days 16-20 of gestation led to suboptimal volume expansion, hypertonicity, and an exaggerated increase in PAVP. These results demonstrate that despite an intravascular space which at term is nearly twice that of virgin rats, pregnant animals secrete AVP in response to fractional volume depletion in a manner similar to nonpregnant controls; that is, the relationship between total blood volume and AVP secretion is altered during gestation such that the expanded blood volume is recognized as normal.

摘要

我们之前观察到,在斯普拉格-道利大鼠孕期,其渗透调节及抗利尿激素分泌的渗透阈值发生了改变,本研究评估了容量对该物种妊娠期精氨酸血管加压素(AVP)释放的影响。未孕动物的基础血浆渗透压(Posm)和血管内容量分别为297±3毫摩尔/千克和16.2±1.2毫升,而妊娠14天的大鼠分别为290±2毫摩尔/千克和20.2±2.3毫升,妊娠21天(接近足月)的大鼠分别为287±3毫摩尔/千克和25.2±2.3毫升(每组妊娠大鼠与未孕大鼠相比,P<0.001)。通过腹腔注射聚乙二醇造成等渗性容量耗竭。容量减少1%至26%,在高达16%的递减过程中血压保持稳定。两组妊娠动物和未孕对照动物的血浆AVP(PAVP)均未显著升高,直到血容量耗竭达到6% - 7%,此后未孕、妊娠14天和妊娠21天的动物体内PAVP以类似的指数方式升高。然而,就绝对变化而言,妊娠大鼠的PAVP在血管内容量仍远大于未孕对照动物的基础血容量时就开始增加。在其他实验中,通过腹腔注射高渗盐水使Posm升高,再次证实妊娠期AVP分泌的渗透阈值降低了约10毫摩尔/千克,并且只要机体张力增加1% - 2%就能刺激AVP释放。在平行研究中,腹腔注射溶解于高渗盐水中的聚乙二醇引起血容量收缩和Posm升高,并将结果与仅接受腹腔注射盐水的动物进行比较。容量减少(约7%),其本身只会使PAVP略有增加,却使分泌反应对渗透压变化的敏感性提高了两到三倍,未孕和妊娠动物的这种效应相似。最后,在妊娠第16 - 20天将妊娠大鼠的水摄入量限制为与未孕大鼠相同,导致容量扩张不理想、高渗状态以及PAVP过度增加。这些结果表明,尽管足月时血管内空间几乎是未孕大鼠的两倍,但妊娠动物对部分容量耗竭分泌AVP的方式与未孕对照动物相似;也就是说,妊娠期总血容量与AVP分泌之间的关系发生了改变,以至于扩张的血容量被视为正常。

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