Original Report: Laboratory Investigation

Angiotensin-(1-7) Prevents Activation of NADPH Oxidase and Renal Vascular Dysfunction in Diabetic Hypertensive Rats
Ibrahim F. Benter^a, Mariam H.M. Yousif^a, Gursev S. Dhaunsi^b, Jaspal Kaur^c, Mark C. Chappell^d, Debra I. Diz^d

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

Address of Corresponding Author

Am J Nephrol 2008;28:25-33 (DOI: 10.1159/000108758)

  Key Words

• Diabetes
• Hypertension
• Angiotensin
• Kidney
• Renal artery

  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.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Ibrahim F. Benter
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University
PO Box 24923
13110 Safat (Kuwait)
Tel. +965 5319 594, Fax +965 5342 583, E-Mail ibenter@hsc.edu.kw

  Article Information

Received: June 28, 2007
Accepted: August 9, 2007
Published online: September 20, 2007
Number of Print Pages : 9
Number of Figures : 7, Number of Tables : 1, Number of References : 41