Original Report: Laboratory Investigation

Hypertension Increases Pro-Oxidant Generation and Decreases Antioxidant Defense in the Kidney in Early Diabetes
Subrata K. Biswas, Elisa B. Peixoto, Denise S. Souza, Jose B. Lopes de Faria

Renal Pathophysiology Laboratory, Division of Nephrology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil

Address of Corresponding Author

Am J Nephrol 2008;28:133-142 (DOI: 10.1159/000109993)

  Key Words

• Diabetes
• Hypertension
• Nephropathy
• Pro-oxidants
• Antioxidants
• Oxidative stress

  Abstract

Aims: The combination of hypertension and diabetes exacerbates renal oxidative stress. The aim of the present study was therefore to evaluate the pro-oxidant and antioxidant mechanisms responsible for the induction of renal oxidative stress in the presence of hypertension and diabetes mellitus. Methods: Diabetes was induced in spontaneously hypertensive rats (SHR) and their genetically normotensive control Wistar-Kyoto (WKY) rats by streptozotocin at 12 weeks of age. After 10 days, pro-oxidant, antioxidant and oxidative stress parameters were evaluated in the renal tissue. Results: NADPH oxidase-dependent superoxide generation in the renal cortex was significantly elevated in WKY and SHR diabetic (D) groups compared to the respective control (C) groups (p < 0.005, n = 5). However, the highest level of superoxide generation was observed in the SHR-D group compared to all other groups. The expression of the gp91phox subunit of NADPH oxidase was significantly elevated in the SHR-D (p < 0.05, n = 5), but not in the WKY-D group, compared to the respective control groups. The renal cortical extracellular-superoxide dismutase level was found to be markedly decreased in the SHR groups compared to the WKY groups (p < 0.05, n = 5). The antioxidant glutathione level was found to be lower in the SHR-D (p = 0.03, n = 15), but not in the WKY-D group, compared to the respective control groups. Finally, nitrotyrosine and 8-hydroxy-2'-deoxyguanosine, markers of oxidative stress, were found to be similar in the kidneys of WKY-C and WKY-D, but were elevated in the SHR-D compared to the SHR-C group. Conclusion: We therefore conclude that hypertension increases pro-oxidant generation and decreases antioxidant defense, and thereby induces renal oxidative stress in early diabetes.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Jose B. Lopes de Faria, MD, PhD
Renal Pathophysiology Laboratory, Division of Nephrology
Department of Internal Medicine, Faculty of Medical Sciences
State University of Campinas, 13084-971 Campinas, São Paulo (Brazil)
Tel. +55 19 3521 7499, Fax +55 19 3521 7366, E-Mail jblfaria@fcm.unicamp.br

  Article Information

This work was supported by grants from Fundacao de Amparo a Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. S.K.B. was the recipient of a scholarship from CAPES.

Received: July 2, 2007
Accepted: August 17, 2007
Published online: October 18, 2007
Number of Print Pages : 10
Number of Figures : 6, Number of Tables : 1, Number of References : 37