ENDOCRINE CONTROL OF FETAL CARDIOVASCULAR DYNAMICS

拟议研究的目的是调查的作用， 激素血管加压素、肾上腺素、去甲肾上腺素、催乳素、肾素和 血管紧张素II对胎儿心血管动力学的调节 正常情况下以及在各种形式的胎儿应激期间。 的 胎儿的内分泌系统在妊娠的最后三分之一是正常的， 各种激素的分泌会随着不同的 紧张的条件。 使用长期插管的胎羊，我们将 探索心率、心输出量、动脉和静脉 血压、血容量和尿量 给予肾上腺素、去甲肾上腺素、催乳素、加压素和 血管紧张素II 这些胎儿激素的循环浓度将 在控制条件下测量，并且响应于体积加载， 缺氧和渗透压变化。 我们将着重于确定 这些激素中的每一种在维持 血压、心率、心输出量和血容量 条件 荷尔蒙变化的特异性和敏感性 通过建立剂量-反应关系、时间-过程 响应，响应幅度与 激素变化的程度，以及特异性拮抗剂的能力， 封锁回应。 这些研究将在胎儿中进行， 妊娠120天至足月（145天），以便比较 不同胎龄的反应。 这些研究将有助于 实现我们的长期目标，了解动态和控制 胎儿的心血管内分泌系统 此外，这些研究可能 有助于为胎儿的治疗提供合理的基础， 新生儿

The purpose of the proposed studies is to investigate the role of the hormones vasopressin, epinephrine, norepinephrine, prolactin, renin, and angiotensin II in the regulation of fetal cardiovascular dynamics under normal conditions as well as during various forms of fetal stress. The fetal endocrine system is functional in the last third of gestation, and the secretion of a variety of hormones changes in response to different stressful conditions. Using chronically catheterized fetal sheep, we will explore changes in heart rate, cardiac output, arterial and venous pressures, blood volume and urinary output in response to exogenously administered epinephrine, norepinephrine, prolactin, vasopressin and angiotensin II. Circulating concentrations of these fetal hormones will be measured during control conditions, and in response to volume loading, hypoxia and osmolality changes. We will place an emphasis on determining the relative importance of each of these hormones in the maintenance of blood presure, heart rate, cardiac output, and blood volume under normal conditions. The specificity and sensitivity of the hormonal changes will be determined by establishing dose-response relationships, time-course of the responses, correlations between the magnitude of the responses and the degree of hormonal changes, and the ability of specific antagonists to block the responses. The studies will be performed in fetuses from 120\days gestation to term (145 days) so as to allow for comparison of responses among different gestational ages. These studies will help to achieve our long-term objective of understanding the dynamics and control of the fetal cardiovascular-endocrine system. In addition, the studies may help provide a rational basis for therapeutic treatment of the fetus and newborn.