Hypertension increases pro-oxidant generation and decreases antioxidant defense in the kidney in early diabetes.
OBJECTIVE
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.


CONCLUSIONS
We therefore conclude that hypertension increases pro-oxidant generation and decreases antioxidant defense, and thereby induces renal oxidative stress in early diabetes.
Biswas
Subrata K
SK
Renal Pathophysiology Laboratory, Division of Nephrology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.
Peixoto
Elisa B
EB
Souza
Denise S
DS
de Faria
Jose B Lopes
JB
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006977:Hypertension, Renal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D016877:Oxidants / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000975:Antioxidants; D008562:Membrane Glycoproteins; D016877:Oxidants; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D005978:Glutathione