ENDOCRINE CONTROL OF FETAL CARDIOVASCULAR DYNAMICS

拟议研究的目的是产生一个 全面了解胎儿的控制 心血管系统的内分泌和自主神经 在正常和压力条件下的系统。 采取的办法 将调查每种激素的作用， 对各种心血管参数感兴趣，然后 评估每种激素在维持 基础条件和各种条件下的胎儿心血管功能 压力的形式。 110只胎羊长期插管 妊娠至足月（145天）作为实验 动物 在第一系列实验中， 静脉输注不同浓度的血管紧张素II， 心钠素或肾上腺素对胎儿动脉和 静脉压、心率、心输出量、血容量， 将测定尿量和血气。 的 精氨酸加压素循环浓度的变化， 血管紧张素II、血浆肾素活性、心钠素和 将同时测量儿茶酚胺。 剂量- 将建立响应关系和时间进程， 每一种注入的激素对每一个心血管 变量 第二系列实验将指导 以确定精氨酸循环水平的变化 血管加压素，血管紧张素II，血浆肾素活性，心房 基础状态下利钠因子和儿茶酚胺 以及对缺氧、出血、高渗等应激的反应 或体积加载。 将试图描绘出 每种激素的相对重要性， 自主神经系统中的激素 在压力条件下维持心血管功能。 第三个系列的实验将被设计来测试 每种激素对维持 在静息状态下心血管功能正常。 在 此外，特定激素对每个人的长期影响 将确定心血管变量。 最后，一个系统 分析方法将被用来帮助理解 胎儿的整体内分泌和自主控制 心血管功能和流体动力学。 这些研究不会 只提供了一个动力学和控制的理解， 胎儿心血管内分泌系统，但也将作为一个 胎儿畸形治疗的合理依据 在子宫内和出生时。

The purpose of the proposed studies is to generate a comprehensive understanding of the control of the fetal cardiovascular system by the endocrine and autonomic nervous systems under normal and stress conditions. The approach taken will be to investigate the effect of each of the hormones of interest on various cardiovascular parameters, and then to evaluate the role of each of the hormones in the maintenance of fetal cardiovascular function during basal conditions and various forms of stress. Chronically catheterized fetal sheep from 110 days gestation to term (145 days) be used as the experimental animal. In the first series of experiments, the effect of intravenous infusion of various concentrations of angiotensin II, atrial natriuretic factor or epinephrine on fetal arterial and venous pressures, heart rate, cardiac output, blood volume, urinary output and the blood gases will be determined. The changes in circulating concentrations of arginine vasopressin, angiotensin II, plasma renin activity, atrial natriuretic factor and the catecholamines will be simultaneously measured. Dose- response relationships and time courses will be established for each of the infused hormones on each of the cardiovascular variables. The second series of experiments will be directed towards determining the changes in circulating levels of arginine vasopressin, angiotensin II, plasma renin activity, atrial natriuretic factor and the catecholamines during basal conditions and in response to stress of hypoxia, hemorrhage, hyperosmolality or volume loading. An attempt will be made to delineate the relative importance of each of the hormones, and the interaction of the hormones with the autonomic nervous system in the maintenance of cardiovascular function under stress conditions. A third series of experiments will be designed to test the contribution of each of the hormones to the maintenance of normal cardiovascular function during resting conditions. In addition, the long-term effects of specific hormones on each cardiovascular variable will be determined. Finally, a systems analysis approach will be taken to assist in the understanding of the overall endocrine and autonomic control of fetal cardiovascular function and fluid dynamics. These studies will not only provide an understanding of the dynamics and control of the fetal cardiovascular-endocrine system, but will also serve as a rational basis for the therapeutic treatment of fetal abnormalities in utero and at birth.