The overall goal of this proposed research is to investigate developmental aspects of endocrine-cardiovascular interactions in the mammalian fetus. This includes determining: (1) if during fetal development neuroendocrine responses to non-hypotensive blood loss are mediated by signals originating from the low pressure side of the cardiovascular system, (2) if during fetal development the neuroendocrine responses to volume loss can be inhibited by neural and/or humoral signals produced by increasing pressure within the low pressure side of the cardiovascular system and finally, (3) if during fetal development the newly discovered hormone, atrial natriuretic factor -ANF, can inhibit neuroendocrine responses to volume loss.
Our aim i s to examine these questions at 0.75 and 0.88 gestation so that ultimately it will be possible to make comparisons of data obtained in both immature and mature fetuses studied under identical, carefully controlled circumstances. The chronically cannulated fetal lamb is the animal model chosen for study. It is possible to study the development of endocrine-cardiovascular relationships in this model in the absence of complications caused by the presence of anesthesia and surgical trauma which are inherent in experiments in acutely prepared animals. The information derived from these proposed studies will further our understanding of the ontogenesis of integration within the endocrine and cardiovascular systems and of the possible role of a new hormone (ANF) in the expression of this integration during development. Increasing our understanding of the maturation of these endocrine-cardiovascular interrelationships may prove pertinent for the improved management of the premature infant or the term infant in distress.

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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Human Embryology and Development Subcommittee 1 (HED)
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Wake Forest University Health Sciences
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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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