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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020299-02
Application #
3318279
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1984-12-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Chan, T T; Richter, P J; Brace, R A (2000) Effect of laboratory acclimation on food and water consumption of pregnant sheep after fetal catheterization. Contemp Top Lab Anim Sci 39:28-31
Johnson, D D; Singh, M B; Cheung, C Y (1997) Effect of three hours of hypoxia on atrial natriuretic factor gene expression in the ovine fetal heart. Am J Obstet Gynecol 176:42-8
Cheung, C Y; Johnson, D D; Reyes, V (1996) Ontogeny of insulin-like growth factor-I and -II gene expression in ovine fetal heart. J Soc Gynecol Investig 3:309-15
Wlodek, M E; Brace, R A; Cock, M L et al. (1995) Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production. Am J Physiol 268:F868-75
Cheung, C Y; Singh, M; Ebaugh, M J et al. (1995) Vascular endothelial growth factor gene expression in ovine placenta and fetal membranes. Am J Obstet Gynecol 173:753-9
Cheung, C Y (1995) Regulation of atrial natriuretic factor secretion and expression in the ovine fetus. Neurosci Biobehav Rev 19:159-64
Cheung, C Y (1994) Regulation of atrial natriuretic factor release by endothelin in ovine fetuses. Am J Physiol 267:R380-6
Brace, R A; Wlodek, M E; McCrabb, G J et al. (1994) Swallowing and urine flow responses of ovine fetuses to 24 h of hypoxia. Am J Physiol 266:R1345-52
Johnson, D D; Tetzke, T A; Cheung, C Y (1994) Gene expression of atrial natriuretic factor in ovine fetal heart during development. J Soc Gynecol Investig 1:14-8
Walker, M P; Moore, T R; Brace, R A (1994) Indomethacin and arginine vasopressin interaction in the fetal kidney: a mechanism of oliguria. Am J Obstet Gynecol 171:1234-41

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