The purpose of this proposed research is to investigate the development of endocrine cardiovascular interactions in the mammalian fetus. This includes defining the basal plasma concentrations of the vasoactive peptides, angiotensin II and vasopressin, and of the catecholamines that exist in the fetus during the last month of gestation and in the neonate during the first two months after birth and correlating changes in these levels with changes in blood pressure and heart rate observed in these same animals during this period. Our goal is also to quantify, in a longitudinal study during late gestation, fetal cardiovascular (blood pressure, cardiac output, heart rate) and hormonal responses to a reduction in blood volume, and to assess the relative importance of vasopressin, angiotensin II and sympatho-adrenal activity in maintaining cardiovascular homeostasis during and after this stress at different times during gestation. The chronically cannulated ovine fetus is the animal model chosen for study. With this model it is possible to study endocrine-cardiovascular interactions in the absence of complications induced by the presence of anesthesia and surgical trauma, both of which are inherent in experiments on acutely prepared animals. These studies are necessary to define the maturational changes in endocrine-cardiovascular interrelationships that occur in the perinatal period. Such information will be useful in understanding the hormonal mechanisms important for the maintenance of fetal cardiovascular function during stress and may prove pertinent for clinical therapy in the premature infant or the term infant distress.

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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Human Embryology and Development Subcommittee 2 (HED)
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Wake Forest University Health Sciences
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United States
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Chappell, Mark C; Al Zayadneh, Ebaa M (2017) Angiotensin-(1-7) and the Regulation of Anti-Fibrotic Signaling Pathways. J Cell Signal 2:
Su, Yixin; Bi, Jianli; Pulgar, Victor M et al. (2017) Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells. Am J Physiol Renal Physiol 312:F1056-F1062
Chen, Kai; Bi, Jianli; Su, Yixin et al. (2016) Sex-Specific Changes in Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 Gene Expression and Enzyme Activity at Birth and Over the First Year of Life. Reprod Sci 23:200-10
Su, Yixin; Bi, Jianli; Pulgar, Victor M et al. (2015) Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner. Am J Physiol Renal Physiol 308:F1268-75
Wilson, Bryan A; Cruz-Diaz, Nildris; Marshall, Allyson C et al. (2015) An angiotensin-(1-7) peptidase in the kidney cortex, proximal tubules, and human HK-2 epithelial cells that is distinct from insulin-degrading enzyme. Am J Physiol Renal Physiol 308:F594-601
Marshall, Allyson C; Pirro, Nancy T; Rose, James C et al. (2014) Evidence for an angiotensin-(1-7) neuropeptidase expressed in the brain medulla and CSF of sheep. J Neurochem 130:313-23
Bi, Jianli; Contag, Stephen A; Chen, Kai et al. (2014) Sex-specific effect of antenatal betamethasone exposure on renal oxidative stress induced by angiotensins in adult sheep. Am J Physiol Renal Physiol 307:F1013-22
Marshall, Allyson C; Shaltout, Hossam A; Pirro, Nancy T et al. (2014) Enhanced activity of an angiotensin-(1-7) neuropeptidase in glucocorticoid-induced fetal programming. Peptides 52:74-81
Bi, Jianli; Contag, Stephen A; Carey, Luke C et al. (2013) Antenatal betamethasone exposure alters renal responses to angiotensin-(1-7) in uninephrectomized adult male sheep. J Renin Angiotensin Aldosterone Syst 14:290-8
Marshall, Allyson C; Shaltout, Hossam A; Nautiyal, Manisha et al. (2013) Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep. Peptides 44:25-31

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