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.
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