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The renin-angiotensin system and the lower urinary tract in diabetes
Summary Data Summary
Applicant Dolber, Paul
E-Mail Address dolber@duke.edu
Project Title The renin-angiotensin system and the lower urinary tract in diabetes
CBU ID 10MCG119
External SubContract ID 20497-45
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2010]
Abstract Nearly 8% of the US population has diabetes, with an additional 26% of adults
over 20 likely to develop diabetes. Urological complications develop in up to
80% of diabetics, the most common being lower urinary tract (LUT) dysfunction.
This is a long-term problem, with changes over time from LUT hyperactivity to
hypoactivity, and seriously compromises the quality of life in diabetics.

Overactivity of the renin-angiotensin system (RAS) is an important component of
diabetes. Its principal product angiotensin II is known to affect the LUT, and
it is known that diabetes itself as well as treatments to reduce angiotensin II
or block its binding to AT1 receptors produce marked changes in the proportions
of AT1 and AT2 receptors which promote contraction and relaxation of smooth
muscle, respectively. Nonetheless, we know next to nothing about RAS
overactivity and LUT function in diabetes. Consequently, we do not know how RAS
overactivity or treatments to reduce it affect diabetic LUT function, nor how
modulation of RAS activity could be harnessed to improve diabetic LUT function.

Our overarching hypothesis is that RAS overactivity in the setting of diabetes
contributes to LUT dysfunction in a time-dependent manner; moreover, treatment
of hypertension and nephropathy in diabetic patients by the inhibition of RAS
overactivity may further contribute to LUT dysfunction. To explore this
hypothesis, we will study mice after 6 or 14 wk of hyperglycemia and with or
without chronic angiotensin II treatment. Our associated specific aims are:

Specific aim 1. Using cystometry and leak-point pressure methodology, determine
the effects of chronic angiotensin II treatment on the LUTs of 129/SvEv mice
with and without Akita diabetes.

Specific aim 2. Using isolated preparations from the bladder and urethra in
vitro, determine the effects of acute and chronic angiotensin II treatment on
LUT contractility in mice with and without Akita diabetes and show the
functional dependence on AT1 vs AT2 receptors.

Specific aim 3. Using fixed LUTs, use histologic and immunohistochemical methods
to determine the effects of diabetes and chronic angiotensin II treatment on the
expression and distribution of angiotensin II and its AT1 and AT2 receptors and
on the smooth muscle and collagen of the LUT.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 45741
Supply Total Costs 8259
Equipment Total Costs 0
Travel/Other Total Costs 3000
Direct Costs 57000
Indirect Costs Proposed 3000
Total Costs Proposed 60000
Total Costs Approved 60000
Start Date 8/1/2010
End Date 7/31/2011
IFO Name Moll, Lorie
IFO E-Mail Address Lorie.Moll@va.gov
IACUC/IRB No. 123456
IACUC/IRB Institution Institute for Medical Research, Inc.
Entity ID No. 56-1655431
Report Request Date 8/31/2011
T1D NO
TypeCount
Invoices 9
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  10MCG11920497-45Institute for Medical Research, Inc.8/8/2012$2,270.28$113.51$2,383.79$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.7/11/2012$2,270.28$113.51$2,383.79$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.5/1/2012$2,270.28$113.51$2,383.79$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.4/2/2012$2,293.38$114.67$2,408.05$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.3/2/2012$2,311.86$115.59$2,427.45$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.2/3/2012$13,221.65$661.08$13,882.73$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.12/1/2011$228.30$11.42$239.72$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.11/1/2011$1,089.93$54.50$1,144.43$32,469.74 
  View  10MCG11920497-45Institute for Medical Research, Inc.1/5/2012$263.34$13.17$276.51$32,469.74 


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