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Alterations in the Brain Renin-Angiotensin System in a Model of Fetal Programming

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abstract
Antenatal betamethasone (BM) is an approved therapy for women threatening early preterm labor between 24 and 34 weeks gestation. The immediate effects of BM therapy are of benefit to the offspring, as fetal steroid exposure decreases infant mortality by accelerating lung and gastrointestinal tract development and activating the sympathetic nervous system. However, fetal steroid exposure may lead to elevated mean arterial pressure and decreased autonomic function in young adults. Baroreflex sensitivity for control of heart rate is an important marker of autonomic function and is reduced in conditions associated with hypertension. Indeed, sheep exposed in utero to BM develop decreased baroreflex sensitivity by 6-weeks of age and increased mean arterial pressure by 6-months of age. These changes in blood pressure and autonomic function are associated with alterations in components of the circulating and intra-renal renin-angiotensin systems (RAS) that shift the RAS to the pro-hypertensive peptide, angiotensin (Ang) II. In the brain, the Ang II AT1 receptor opposes the beneficial actions of Ang-(1-7) at the Mas receptor for control of baroreflex sensitivity and blood pressure regulation. Our goal was to identify BM induced alterations in the central RAS that are consistent with functional data reporting increased pressure and decreased baroreflex function. This dissertation focuses on the RAS peptides, receptors, and enzymes that act as possible sites of BM induced alterations.
subject
Brain
Fetal programming
Peptidase
Renin-angiotensin system
contributor
Marshall, Allyson Catherine (author)
Chappell, Mark C (committee chair)
Taylor, Robert N (committee member)
Washburn, Lisa K (committee member)
Shaltout, Hossam A (committee member)
date
2014-07-10T08:35:27Z (accessioned)
2014-07-10T08:35:27Z (available)
2014 (issued)
degree
Physiology and Pharmacology (discipline)
identifier
http://hdl.handle.net/10339/39262 (uri)
language
en (iso)
publisher
Wake Forest University
title
Alterations in the Brain Renin-Angiotensin System in a Model of Fetal Programming
type
Dissertation

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