VASOPRESSIN SECRETION AND OSMOREGULATION IN PREGNANCY

本提案的目的是阐明机制 导致血浆渗透压和渗透压降低 妊娠期间AVP释放的阈值。 具体目标是：（1）测试 假设怀孕期间的月经调节变化是由于 “有效血容量”减少或其他血液动力学改变 影响AVP分泌。 (2)使用体外 下丘脑-神经垂体外植体确定a）AVP分泌是否 在妊娠期增加，B）如果妊娠期月经调节变化是由于 c）妊娠期AVP分泌是否改变 依赖于下丘脑和/或垂体的传入神经输入。 建议的实验是：I.测定肾脏、体液、血液动力学和 慢性容量负荷对妊娠大鼠的神经调节反应 与摄入正常或钠的动物相比， 限制饮食。 二.检查妊娠大鼠的神经调节反应 接受慢性血管收缩剂治疗。 三.企图繁殖 模拟未孕大鼠妊娠的神经调节变化 妊娠期血流动力学和激素变化通过生产 动静脉瘘联合慢性雌激素治疗。 四. 在体外测定基础的和刺激的AVP分泌， 孕鼠不同时期下丘脑-垂体神经组织 使用器官移植和灌注方法进行妊娠。 的影响 在未交配和怀孕动物的血浆中孵育神经组织， 还将研究AVP分泌。 加压素与几种形式的高血压有关。 更 重要的是，体积稳态、水代谢、AVP分泌和 对正常妊娠的血压控制仍然知之甚少。 从目前的调查中获得的信息将有助于更好地 了解这些生理过程，并可能导致改善 高血压和/或肾功能不全的孕妇的护理 疾病，其中水处理和体积调节是 明显异常

The objective of the present proposal is elucidation of mechanism(s) responsible for decrements in both plasma osmolality and the osmotic threshold for AVP release during gestation. Specific aims are: (1) Test the hypothesis that changes in osmoregulation during pregnancy are due a decrease in "effective blood volume" or to other hemodynamic alterations which affect AVP secretion. (2) Using an in vitro hypothalamo-neurohypophysial explant determine a) whether AVP secretion is increased in pregnancy, b) if gestational osmoregulatory changes are due to a circulating factor and, c) whether AVP secretory alterations in pregnancy are dependent on afferent neural input to the hypothalamus and/or pituitary. Proposed experiments are: I. Determine renal, humoral, hemodynamic and osmoregulatory responses of gravid rats subjected to chronic volume expansion comparing them with animals ingesting a normal or sodium restricted diet. II. Examine osmoregulatory responses of gravid rats subjected to chronic vasoconstrictor treatment. III. Attempt to reproduce the osmoregulatory changes of pregnancy in virgin rats by mimicking gestational hemodynamic and hormonal alterations via production of arterio-venous fistula in combination with chronic estrogen therapy. IV. Determine basal and osmotically stimulated AVP secretion in vitro from hypothalamo-neurohypophysial tissue of gravid rats at various stages of gestations using organ explant and perifusion methodologies. The effects of incubating neural tissue in plasma from virgin and pregnant animals on AVP secretion will also be studied. Vasopressin has been implicated in several forms of hypertension. More importantly, volume homeostasis, water metabolism, AVP secretion and control of blood pressure in normal pregnancy remain poorly understood. Information gained from present investigations will contribute to a better understanding of these physiologic processes and may lead to improvements in the care of pregnant patients with high blood pressure and/or renal disease, disorders in which water handling and volume regulation are markedly abnormal.