Angiotensin II (AII) dependent alterations in renal hemodynamics and excretory function contribute to the development and maintenance of high blood pressure in some forms of hypertension. This proposal focuses on the novel hypertensive transgenic rat (TGR) constructed by inserting the mouse ren2 renin gene into the rat genome. The hypertension that develops in this model occurs as a consequence of overexpression of the mouse ren2 renin gene and provides a unique opportunity to determine the specific mechanisms whereby inappropriate activation of the renin angiotensin system lead to vasoconstriction, excessive salt and water retention and hypertension. The overall objective of these studies is to define and characterize the derangements in renal hemodynamics and tubular reabsorptive function that occur during development and maintenance of hypertension in ren2 transgenic rats. In vivo micropuncture studies will assess the AII dependency of changes in proximal tubular reabsorption and tubuloglomerular feedback responsiveness before, during development and in the maintenance phase of the hypertension. Further studies will evaluate the contribution of aldosterone to the hypertension and the renal vascular responsiveness to vasoactive agents. These studies will provide new information on the role of AII dependent alterations in renal function in the ren2 model of hypertension and may also give insight into renal function derangements in essential hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL050438-01A2
Application #
2226631
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1995-01-01
Project End
1998-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Tulane University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Wang, Chi-Tarng; Navar, L Gabriel; Mitchell, Kenneth D (2003) Proximal tubular fluid angiotensin II levels in angiotensin II-induced hypertensive rats. J Hypertens 21:353-60