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Original Report: Laboratory Investigation

Angiotensin-(1–7) Prevents Activation of NADPH Oxidase and Renal Vascular Dysfunction in Diabetic Hypertensive Rats

Benter I.F.a · Yousif M.H.M.a · Dhaunsi G.S.b · Kaur J.c · Chappell M.C.d · Diz D.I.d

Author affiliations

Departments of aPharmacology and Toxicology and bPediatrics, Faculty of Medicine, Kuwait University, Kuwait; cDepartment of Pediatrics, University of Virginia, Charlottesville, Va., and dThe Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, N.C., USA

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Am J Nephrol 2008;28:25–33

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Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: June 28, 2007
Accepted: August 09, 2007
Published online: September 20, 2007
Issue release date: November 2007

Number of Print Pages: 9
Number of Figures: 7
Number of Tables: 1

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: https://www.karger.com/AJN

Abstract

Background/Aim: We examined the influence of chronic treatment with angiotensin-(1–7) [Ang-(1–7)] on renox (renal NADPH oxidase, NOX-4) and the development of renal dysfunction in streptozotocin-treated spontaneously hypertensive rats (diabetic SHR). Methods:Mean arterial pressure, urinary protein and vascular responsiveness of the isolated renal artery to vasoactive agonists were studied in vehicle- or Ang-(1–7)-treated SHR and diabetic SHR. Results: Ang-(1–7) decreased the elevated levels of renal NADPH oxidase (NOX) activity and attenuated the activation of NOX-4 gene expression in the diabetic SHR kidney. Ang-(1–7) treatment increased sodium excretion but did not affect mean arterial pressure in diabetic SHR. There was a significant increase in urinary protein (266 ± 22 mg/24 h) in the diabetic compared to control SHR (112 ± 13 mg/24 h) and treatment of diabetic SHR with Ang-(1–7) reduced the degree of proteinuria (185 ± 23 mg/24 h, p < 0.05). Ang-(1–7) treatment also attenuated the diabetes-induced increase in renal vascular responsiveness to endothelin-1, norepinephrine, and angiotensin II in SHR, but significantly increased the vasodilation of the renal artery of SHR and diabetic SHR to the vasodilator agonists. Conclusion: These results suggest that treatment with Ang-(1–7) constitutes a potential therapeutic strategy to alleviate NOX-mediated oxidative stress and to reduce renal dysfunction in diabetic hypertensive rats.

© 2007 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: June 28, 2007
Accepted: August 09, 2007
Published online: September 20, 2007
Issue release date: November 2007

Number of Print Pages: 9
Number of Figures: 7
Number of Tables: 1

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: https://www.karger.com/AJN


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