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Dynamics of BP transmission and hypertensive renal injury

Award Number: R01DK040426
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/1990
PERIOD OF PERFORMANCE END DATE: 03/31/2014

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Dynamics of BP transmission and hypertensive renal injury - DESCRIPTION (provided by applicant): Despite substantial progress several fundamental issues of hypertensive renal damage remain unresolved. (1) The term 'BP load' is still used genetically due to the complexity of the BP phenotype because of its fundamental lability and oscillating phenotype and because the relative pathogenic importance of individual BP parameters (components) remains poorly defined. (2) Likewise, the real time renal transmission of the fluctuating BP must be a dynamic process, but methods to assess such transmission in the conscious unanaesthetized state remain to be developed and validated. (3) Although an impairment of protective renal autoregulation (AR) is recognized to play a central role in the enhanced BP transmission and the increased susceptibility of chronic kidney disease patients to hypertensive induced renal damage (HERD), the responsible mechanisms remain obscure. Specific Aim 1 is addressed to the question - - what is the pathogenetically relevant definition of the "aggregate BP load" for the renal vascular bed. We will test the hypothesis that a more precise quantitation of "BP load" may be achieved by a biophysical estimation of the BP energy and its individual components for correlation with HIRD. This will be performed in rats with remnant kidneys because of their enhanced susceptibility to HIRD. Suboptimal antihypertensive therapy will be used to increase the natural variability of the "BP load" components. Multivariant analysis will be used to examine the separate or combined contribution of the individual "BP load" components to renal damage. Specific Aim 2 is addressed to the assessment of dynamic BP transmission in conscious rats. Our studies have shown that in contrast to the currently used but poorly predictive parameters, transfer function analysis of the admittance gain at the heart beat frequency and the magnitude of the myogenic resonance peak might provide better indices. The validity of these proposed parameters will be examined by their correlations and/or correspondence with the magnitude and/or kinetics of the AR response during step changes in BP in several models in which such step responses have shown excellent correlations with susceptibility to HIRD. Specific Aim 3 will address the mechanisms responsible for the impaired renal AR in afferent arterioles isolated from remnant kidneys. Our preliminary results have suggested that the inward rectifier potassium channel (Kir) that plays a major role in the pressure induce depolarization and myogenic responses and its function, is altered in remnant kidneys. Further characterization of the altered signal transduction mechanisms will be performed in similarly isolated afferent arterioles and myocytes using techniques that are well established in Dr. Loutzenhiser's laboratory. We believe that the collective expertise of the investigative team is uniquely equipped to address these fundamental questions in the pathogenesis of HIRD.


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: 2014 ( Subtotal = $0 )
2014	2011	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	4/7/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $239,990 )
2011	2011	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	7/8/2011	NON-COMPETING CONTINUATION	$239,990
														Subtotal = $239,990

Issue Date FY: 2010 ( Subtotal = $242,143 )
2010	2010	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	4/1/2010	NON-COMPETING CONTINUATION	$242,143
														Subtotal = $242,143

Issue Date FY: 2009 ( Subtotal = $329,931 )
2009	2009	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Trans-NIH Recovery Act Research Support	001	17	8/31/2009	SUPPLEMENT FOR EXPANSION	$85,608
2009	2009	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	3/10/2009	NON-COMPETING CONTINUATION	$244,323
														Subtotal = $329,931

Issue Date FY: 2008 ( Subtotal = $244,065 )
2008	2008	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	16	3/12/2008	NON-COMPETING CONTINUATION	$244,065
														Subtotal = $244,065

Issue Date FY: 2007 ( Subtotal = $260,783 )
2007	2007	CHICAGO ASSOCIATION FOR RESEARCH & ED IN SCIENCE	BLDG ONE RM C307PO BOX 250	HINES	IL	60141	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	15	3/12/2007	COMPETING CONTINUATION	$260,783
														Subtotal = $260,783

Issue Date FY: 2004 ( Subtotal = $293,875 )
2004	2004	LOYOLA UNIVERSITY MEDICAL CENTER							Kidney Diseases, Urology and Hematology Research	000	14	5/20/2004	NON-COMPETING CONTINUATION	$293,875
														Subtotal = $293,875

Issue Date FY: 2003 ( Subtotal = $293,875 )
2003	2003	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	13	6/23/2003	NON-COMPETING CONTINUATION	$293,875
														Subtotal = $293,875

Issue Date FY: 2002 ( Subtotal = $293,875 )
2002	2002	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	12	6/10/2002	NON-COMPETING CONTINUATION	$293,875
														Subtotal = $293,875

Issue Date FY: 2001 ( Subtotal = $305,755 )
2001	2001	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	11	7/16/2001	COMPETING CONTINUATION	$305,755
														Subtotal = $305,755

Issue Date FY: 2000 ( Subtotal = $260,825 )
2000	2000	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	10	12/3/1999	NON-COMPETING CONTINUATION	$260,825
														Subtotal = $260,825

Issue Date FY: 1999 ( Subtotal = $253,164 )
1999	1999	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	9	2/6/1999	NON-COMPETING CONTINUATION	$253,164
														Subtotal = $253,164

Issue Date FY: 1998 ( Subtotal = $246,385 )
1998	1998	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Kidney Diseases, Urology and Hematology Research	000	8	11/30/1997	NON-COMPETING CONTINUATION	$246,385
														Subtotal = $246,385

Grand Total All Awards = $3,264,666

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Dynamics of BP transmission and hypertensive renal injury

Award Number: R01DK040426

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/1990

PERIOD OF PERFORMANCE END DATE: 03/31/2014

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