Xu Z, Glenda C, Day L, Yao J, Ross M G
Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Harbor-University of California Los Angeles (UCLA) Research and Education Institute, Harbor UCLA-Medical Center, Torrance, California 90502, USA.
Am J Physiol Endocrinol Metab. 2000 Dec;279(6):E1207-15. doi: 10.1152/ajpendo.2000.279.6.E1207.
In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 +/- 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.
在成年人中，高渗状态刺激中枢渗透压感受器，导致精氨酸加压素（AVP）分泌。接近足月的胎羊也已形成对血管内高渗状态作出反应的机制，刺激子宫内AVP释放。然而，先前证明胎儿AVP分泌的研究使用的血浆张力变化大于成年人渗透压诱导AVP刺激所需的变化。我们试图研究接近足月胎儿的血浆渗透压阈值和刺激AVP分泌的敏感性，并将血浆激素水平与中枢神经元反应性相关联。长期植入仪器的绵羊胎儿（130±2天）和母羊同时接受等渗或高渗血管内NaCl输注。在血浆高渗状态逐渐增加时，检测母羊和胎儿血浆中的AVP和血管紧张素II（ANG II）水平。静脉内高渗NaCl逐渐升高血浆渗透压和钠水平。高渗状态期间，母羊和胎儿血浆中的AVP均增加，而ANG II水平未改变。血浆渗透压增加3%时，母羊AVP水平显著增加，而胎儿血浆AVP仅在较高血浆渗透压水平（超过6%）时才显著增加。因此，尽管母羊和胎儿AVP分泌的血浆渗透压阈值相似（302对304 mosmol/kg），但AVP与渗透压回归曲线的斜率母羊大于胎儿（0.232对0.064）。高渗状态诱导胎儿脑室内器官中的Fos免疫反应性（FOS-ir）。在胎儿视上核和室旁核（SON和PVN）中也证实有FOS-ir，双重标记显示SON和PVN中含AVP的神经元对静脉内NaCl有反应而表达Fos。这些结果表明，在妊娠130天的绵羊胎儿中，对细胞脱水的神经内分泌反应是有功能的，尽管与成年人相比，它们对AVP分泌的敏感性相对降低。
