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FETAL ENDOCRINE-CARDIOVASCULAR RELATIONS

Award Number: R01HD017644
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/1984
PERIOD OF PERFORMANCE END DATE: 11/30/2013

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FETAL ENDOCRINE-CARDIOVASCULAR RELATIONS - Substantial evidence suggests that events occurring prenatally have long term effects on development extending to adulthood. The outcome of some of these effects is a predisposition to certain diseases including hypertension. Some evidence indicates that these predisposing events involve exposure of the fetus to high levels of glucocorticoids at critical stages of development and that one potential target organ is the kidney. However, our understanding of the changes in renalfunction resulting from the "programming" effects of glucocorticoids and the mechanisms involved is almost non-existent. Therefore, the objective of this project is to define the mechanisms whereby exposure of thefetus to a clinically relavent dose of glucocorticoids at a crucialperiod of gestation (peak of nephrogenesis) affects sodium handling and blood pressure in the adult. We will study a widely used animal model, the sheep, because it is similar to humans in terms of the timing of nephrogenesis relative to stage of gestation and these animals will provide sufficient quanties of renal tissue for our in vitro studies. Wehypothesize that: 1) Glucocorticoid exposure prenatally reduces nephron number and results in alterations in the intrarenal renin-angiotensin system (RAS) including increases in the ratio ofangiotensin converting enzyme to angiotensin converting enzyme2, consequent changes in theAngII to Ang-(l-7)balance andinadequatefeedback regulation of the RASlater in life; and, 2) these changes will be accompanied by impaired sodium excretion resulting from alterations in sodium transport and will increase blood pressure. We will use specific assays for the various angiotensin peptides (Ang I, Ang II and Ang 1-7), assays of enzyme and sodium transporter activity, localization procedures (immunocytochemistry and autoradiography) and molecular techniques to systematically evaluate components of the intrarenal and systemic RAS and sodium handling by the kidney in control and glucocorticoid exposed groups. A combination of in vitro and in vivo studies will be employed at different stages of maturation to establish the relationships between alterations in the RAS, sodium handling, and blood pressure. Understanding more about the impact of glucocorticoids on these inter- relationships is important because of the current use of antenatal steroids in obstetrics to enhance fetal lung maturation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	25	12/12/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $254,326 )
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	001	25	5/25/2011	NON-COMPETING CONTINUATION	$15,895
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	25	11/29/2010	NON-COMPETING CONTINUATION	$238,431
														Subtotal = $254,326

Issue Date FY: 2010 ( Subtotal = $264,923 )
2010	2010	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	001	24	3/9/2010	NON-COMPETING CONTINUATION	$24,084
2010	2010	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	24	12/10/2009	NON-COMPETING CONTINUATION	$240,839
														Subtotal = $264,923

Issue Date FY: 2009 ( Subtotal = $267,599 )
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	23	11/26/2008	NON-COMPETING CONTINUATION	$240,839
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	001	23	4/7/2009	NON-COMPETING CONTINUATION	$26,760
														Subtotal = $267,599

Issue Date FY: 2008 ( Subtotal = $267,599 )
2008	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	22	12/3/2007	NON-COMPETING CONTINUATION	$267,599
														Subtotal = $267,599

Issue Date FY: 2007 ( Subtotal = $271,984 )
2007	2007	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	21	2/9/2007	COMPETING CONTINUATION	$271,984
														Subtotal = $271,984

Issue Date FY: 2004 ( Subtotal = $293,625 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	20	8/19/2004	NON-COMPETING CONTINUATION	$293,625
														Subtotal = $293,625

Issue Date FY: 2003 ( Subtotal = $293,625 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Child Health and Human Development Extramural Research	000	19	7/30/2003	NON-COMPETING CONTINUATION	$293,625
														Subtotal = $293,625

Issue Date FY: 2002 ( Subtotal = $293,625 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Child Health and Human Development Extramural Research	000	18	7/25/2002	NON-COMPETING CONTINUATION	$293,625
														Subtotal = $293,625

Issue Date FY: 2001 ( Subtotal = $293,625 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Child Health and Human Development Extramural Research	000	17	7/20/2001	NON-COMPETING CONTINUATION	$293,625
														Subtotal = $293,625

Issue Date FY: 2000 ( Subtotal = $293,625 )
2000	2000	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Child Health and Human Development Extramural Research	000	16	8/23/2000	COMPETING CONTINUATION	$293,625
														Subtotal = $293,625

Issue Date FY: 1999 ( Subtotal = $184,106 )
1999	1999	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Child Health and Human Development Extramural Research	000	15	4/16/1999	NON-COMPETING CONTINUATION	$184,106
														Subtotal = $184,106

Issue Date FY: 1998 ( Subtotal = $177,025 )
1998	1998	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Child Health and Human Development Extramural Research	000	14	3/26/1998	NON-COMPETING CONTINUATION	$177,025
														Subtotal = $177,025

Grand Total All Awards = $3,155,687

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FETAL ENDOCRINE-CARDIOVASCULAR RELATIONS

Award Number: R01HD017644

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/1984

PERIOD OF PERFORMANCE END DATE: 11/30/2013

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