VASOPRESSIN SECRETION AND OSMOREGULATION IN PREGNANCY

本建议的目的是阐明机制(S) 负责降低血浆渗透压和渗透压 妊娠期AVP释放阈值。具体目标是：(1)测试 认为怀孕期间渗透调节的变化是由于 “有效血容量”的减少或其他血液动力学改变 会影响血管紧张素转运蛋白的分泌。(2)使用体外培养的 下丘脑-神经垂体外植体决定a)AVP分泌是否 怀孕期间增加，b)如果妊娠渗透调节变化是由于 A循环因子和，c)妊娠期间AVP是否发生分泌改变 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、血流动力学和 妊娠大鼠对慢性容量的渗透调节反应 将它们与摄入正常或钠的动物进行比较 限制饮食。II.检测妊娠大鼠的渗透压调节反应 接受慢性血管收缩药治疗。三、试图繁殖 模拟处女大鼠妊娠过程中渗透压的变化 孕期血液动力学和激素变化通过产生 动静脉瘘联合慢性雌激素治疗。四、 体外测定基础和渗透刺激的AVP分泌 不同孕期妊娠大鼠下丘脑-神经垂体组织的变化 使用器官移植和灌流方法进行妊娠。其影响 在血浆中孵育处女和怀孕动物的神经组织 AVP的分泌也将被研究。 加压素被认为与几种形式的高血压有关。更多 重要的是，容量动态平衡、水分代谢、AVP分泌和 对正常妊娠时血压的控制仍然知之甚少。 从目前调查中获得的信息将有助于更好地 对这些生理过程的理解，并可能导致改进 在护理患有高血压和/或肾脏的孕妇时 疾病，水处理和水量调节的紊乱 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.