Losartan exerts renoprotection through NAD(P)H oxidase downregulation in a renovascular model of hypertension.
This study was performed to provide insight into the regulatory role of angiotensin II and arterial pressure on the activity of antioxidant enzymes and oxidative stress generation in the hypertensive kidney from an experimental animal model of renovascular hypertension. Aortic coarcted and sham-operated rats received vehicle, losartan or minoxidil in their drinking water. After 7 d of treatment rats were sacrificed; hypertensive kidneys were excised, and the NAD(P)H oxidase subunits expression, TBARS production, glutathione level and the activity of heme oxygenase-1 and classical antioxidant enzymes, were evaluated. Losartan administration significantly reduced oxidative stress generation decreasing NAD(P)H oxidase expression, independently of the drop in arterial pressure. On the other hand, antioxidant enzymes were regulated by arterial pressure and they were not implicated in kidney protection against oxidative damage. Findings here reported strongly suggest that clinical therapeutics with the Ang II type 1 receptor blocker prevents oxidative stress generation and may attenuate the kidney oxidative damage in the renovascular hypertension. We hypothesize that the pathway followed by the Ang II blocker to achieve this renoprotection, though independent of the primary antioxidant enzymatic system, depends on NAD(P)H oxidase downregulation.
Polizio
Ariel H
AH
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (1113), Buenos Aires, Argentina.
Balestrasse
Karina B
KB
Gornalusse
German G
GG
Gorzalczany
Susana B
SB
Santa-Cruz
Diego M
DM
Yannarelli
Gustavo G
GG
Peña
Clara
C
Tomaro
María L
ML
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015153:Blotting, Western; D015536:Down-Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000188:drug therapy; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D047228:Angiotensin II Type 1 Receptor Blockers; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; D005978:Glutathione; D019808:Losartan