ENDOCRINE CONTROL OF FETAL CARDIOVASCULAR DYNAMICS

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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.