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PRENATAL GLUCOCORTICOID AND POSTNATAL BLOOD PRESSURE

Award Number: R01HL068728
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2001
PERIOD OF PERFORMANCE END DATE: 11/30/2014

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PRENATAL GLUCOCORTICOID AND POSTNATAL BLOOD PRESSURE - DESCRIPTION (provided by applicant): Extensive data in experimental animals indicate that fetal exposure to glucocorticoids (GC) is associated with long term effects, however, the mechanisms remain largely unknown. During the previous funding period we showed that a single course of betamethasone elevates arterial blood pressure in the adult offspring and is associated with a 25% decrease in nephron number, but without an impairment of renal function, and alterations in vascular reactivity compatible with a dysfunction of the endothelin system. In humans and in animals, antenatal GC exposure is associated with glucose tolerance abnormalities. In this competitive continuation we will test the hypothesis that .A derangement in the endothelin system plays a central causative role in the long-term cardiovascular and metabolic abnormalities present in adults exposed antenatally to glucocorticoids.. Specifically we hypothesize that in the adult offspring exposed antenatally to glucocorticoids: 1) The upregulation of the endothelin (ET) system plays a central role in the development of hypertension and glucose intolerance/insulin resistance; 2) There is a synergistic interaction between antenatal glucocorticoid exposure and obesity that exaggerates the cardiovascular and metabolic effects of the ET system; 3) Following antenatal steroid exposure the development of insulin resistance establishes a positive feedback loop and enhances the contribution of the endothelin system to the increase in arterial blood pressure. We will test these hypotheses with the following specific aims: Specific Aim 1: To determine if the ET system contributes to the development of hypertension following antenatal glucocorticoid exposure. Specific Aim 2: To determine if diet-induced obesity exacerbates the cardiovascular and metabolic effects of the endothelin system in glucocorticoid exposed animals. Specific Aim 3: To determine the interactions of obesity/insulin resistance and the endothelin system on the cardiovascular and metabolic effects of antenatal glucocorticoid exposure. Given the increasing incidence of obesity and the mounting evidence for a developmental origin of cardiovascular disease, the studies proposed will determine the role of the ET-1 system and the interaction between antenatal glucocorticoid exposure and obesity. PUBLIC HEALTH RELEVANCE: In humans and in animals, antenatal glucocorticoid exposure is associated with elevations in blood pressure and glucose tolerance abnormalities. The proposed studies will determine if the endothelin system plays a critical role in the development of these abnormalities and if obesity in adulthood magnifies the alterations already present in those exposed prenatally to glucocorticoid. This information will aid in establishing new preventive interventions and therapeutic approaches in populations at risk for developing hypertension in adult life.


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 = $344,670 )
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	9	7/2/2013	NON-COMPETING CONTINUATION	$18,827
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	9	11/23/2012	NON-COMPETING CONTINUATION	$325,843
														Subtotal = $344,670

Issue Date FY: 2012 ( Subtotal = $358,530 )
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	8	11/14/2011	NON-COMPETING CONTINUATION	$365,701
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	8	3/2/2012	NON-COMPETING CONTINUATION	-$7,171
														Subtotal = $358,530

Issue Date FY: 2011 ( Subtotal = $356,722 )
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	7	11/19/2010	NON-COMPETING CONTINUATION	$326,414
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	7	7/25/2011	NON-COMPETING CONTINUATION	$30,308
														Subtotal = $356,722

Issue Date FY: 2010 ( Subtotal = $434,931 )
2010	2010	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	6	1/8/2010	COMPETING CONTINUATION	$434,931
														Subtotal = $434,931

Issue Date FY: 2006 ( Subtotal = $351,540 )
2006	2006	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Lung Diseases Research	000	5	11/29/2005	NON-COMPETING CONTINUATION	$351,540
														Subtotal = $351,540

Issue Date FY: 2005 ( Subtotal = $360,000 )
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Lung Diseases Research	000	4	12/2/2004	NON-COMPETING CONTINUATION	$360,000
														Subtotal = $360,000

Issue Date FY: 2004 ( Subtotal = $360,000 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Lung Diseases Research	000	3	11/20/2003	NON-COMPETING CONTINUATION	$360,000
														Subtotal = $360,000

Issue Date FY: 2003 ( Subtotal = $360,000 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Lung Diseases Research	000	2		NON-COMPETING CONTINUATION	$360,000
														Subtotal = $360,000

Issue Date FY: 2002 ( Subtotal = $360,729 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Lung Diseases Research	000	1	11/30/2001	NEW	$360,729
														Subtotal = $360,729

Grand Total All Awards = $3,287,122

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PRENATAL GLUCOCORTICOID AND POSTNATAL BLOOD PRESSURE

Award Number: R01HL068728

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2001

PERIOD OF PERFORMANCE END DATE: 11/30/2014

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