The Animal Core provides the investigators with chronically instrumented sheep and with non instrumented pregnant and nonpregnant animals. The specific goals of the Animal Core are: to obtain time- dated pregnant animals at 75 days of gestation;to prepare chronically instrumented juvenile and adult sheep for use in the different research projects;to conduct necropsies and facilitate the collection of tissues; and to facilitate the in vivo studies involving monitoring physiologic variables under acute or chronic conditions. Pregnant ewes are randomly assigned to receive either vehicle or betamethasone injections at 80 an 81 days gestation and lambs are allowed to deliver spontaneously at term. The Animal Core is essential for three of the research projects. The director of the core has more than 25 years of experience working with chronically instrumented fetal and pregnant animals. The Core provides the unique combination of the ability to infuse physiological amounts of putative regulators, the availability of plasma samples, in vivo recording of physiological variables and tissues for in vitro studies from the same animal in which in vivo studies have been conducted. Sheep will be chronically instrumented in order to obtain physiological data in animals that are not under the stress of anesthesia. We will use fime dated pregnant sheep provided to us by Hash, Inc. The supplies maintains a very large flock and has consistently provided us with healthy and accurately dated pregnant animals. All of these surgeries and manipulafions will be conducted within the Animal Core in the Perinatal Research Laboratory. Pregnant and adult sheep of both genders will be used. Betamethasone is administered in a manner similar to that used for stimulafing lung maturafion in the unborn human, i.e., two doses of a mixture of the acetate and phosphate form, given 24 hours apart. The only difference is that we will adjust for maternal body weight and give 0.17 mg/kg with a maximum of 12 mg/day.

Public Health Relevance

The animal core plays a central role as it coordinates the breeding, the surgeries and the necropsies for the different projects. It provides investigators with the expertise to instrument animal for either chronic or acute studies. Centralization of animal requirements translates in a more efficient operation that results in better use of the animal resources and reduces the total number of animals.

National Institute of Health (NIH)
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Special Emphasis Panel (ZHD1)
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Wake Forest University Health Sciences
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Washburn, Lisa K; Brosnihan, K Bridget; Chappell, Mark C et al. (2015) The renin-angiotensin-aldosterone system in adolescent offspring born prematurely to mothers with preeclampsia. J Renin Angiotensin Aldosterone Syst 16:529-38
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
Wilson, Bryan A; Marshall, Allyson C; Alzayadneh, Ebaa M et al. (2014) The ins and outs of angiotensin processing within the kidney. Am J Physiol Regul Integr Comp Physiol 307:R487-9
Chappell, Mark C; Marshall, Allyson C; Alzayadneh, Ebaa M et al. (2014) Update on the Angiotensin converting enzyme 2-Angiotensin (1-7)-MAS receptor axis: fetal programing, sex differences, and intracellular pathways. Front Endocrinol (Lausanne) 4:201
Lee, J-H; Zhang, J; Massmann, G A et al. (2014) Antenatal betamethasone increases vascular reactivity to endothelin-1 by upregulation of CD38/cADPR signaling. J Dev Orig Health Dis 5:56-62
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
Nixon, P A; Washburn, L K; O'Shea, T M (2013) Antenatal steroid exposure and pulmonary outcomes in adolescents born with very low birth weight. J Perinatol 33:806-10
Washburn, Lisa; Nixon, Patricia; Russell, Gregory et al. (2013) Adiposity in adolescent offspring born prematurely to mothers with preeclampsia. J Pediatr 162:912-7.e1
Marshall, Allyson C; Shaltout, Hossam A; Pirro, Nancy T et al. (2013) Antenatal betamethasone exposure is associated with lower ANG-(1-7) and increased ACE in the CSF of adult sheep. Am J Physiol Regul Integr Comp Physiol 305:R679-88

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