Abstract

Two types of angiotensin II receptors, AT1 and AT2, have been described. The majority of studies suggest that the renal actions of angiotensin II are mediated by angiotensin AT1 receptors. The physiologic actions of angiotensin II at the AT2 receptor have been difficult to elicit. Preliminary studies suggest that AT1 and AT2 have mutually counteracting hemodynamic effects. Dr. Siragy has utilized a novel renal interstitial microdialysis technique to evaluate the hypothesis that renal AT2 receptor physiologically modulates the renal production of bradykinin, nitric oxide and eicosanoids.
The specific aims for this proposal are: 1) To test the hypothesis that AT2 receptor modulates renal production of bradykinin and nitric oxide. 2) To test the hypothesis that AT2 receptor influences renal eicosanoids through modulation of prostaglandin E 9-ketoreductase and nitric oxide generation. The proposed studies are related to the long term goal of increased understanding of the pathophysiology of body sodium and water excretion abnormalities and hypertension.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057503-04
Application #
6183839
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Barouch, Winifred
Project Start
1997-08-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2000
Total Cost
$227,303
Indirect Cost

  Institution

Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Abadir, Peter M; Periasamy, Ammasi; Carey, Robert M et al. (2006) Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension 48:316-22
Xue, Chun; Siragy, Helmy M (2005) Local renal aldosterone system and its regulation by salt, diabetes, and angiotensin II type 1 receptor. Hypertension 46:584-90
Siragy, Helmy M; Xue, Chun; Abadir, Peter et al. (2005) Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation. Hypertension 45:133-7
Awad, Alaa S; Webb, Randy L; Carey, Robert M et al. (2005) Increased renal production of angiotensin II and thromboxane B2 in conscious diabetic rats. Am J Hypertens 18:544-8
Awad, Alaa S; Webb, Randy L; Carey, Robert M et al. (2004) Renal nitric oxide production is decreased in diabetic rats and improved by AT1 receptor blockade. J Hypertens 22:1571-7
Siragy, Helmy M (2004) AT1 and AT2 receptor in the kidney: role in health and disease. Semin Nephrol 24:93-100
Siragy, Helmy M; Awad, Alaa; Abadir, Peter et al. (2003) The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-alpha in diabetic rats. Endocrinology 144:2229-33
Kalantarinia, Kambiz; Awad, Alaa S; Siragy, Helmy M (2003) Urinary and renal interstitial concentrations of TNF-alpha increase prior to the rise in albuminuria in diabetic rats. Kidney Int 64:1208-13
Abadir, Peter M; Carey, Robert M; Siragy, Helmy M (2003) Angiotensin AT2 receptors directly stimulate renal nitric oxide in bradykinin B2-receptor-null mice. Hypertension 42:600-4
Millatt, Lesley J; Whitley, Guy StJ; Li, Dechun et al. (2003) Evidence for dysregulation of dimethylarginine dimethylaminohydrolase I in chronic hypoxia-induced pulmonary hypertension. Circulation 108:1493-8

Showing the most recent 10 out of 23 publications