Losartan exerts renoprotection through NAD(P)H oxidase downregulation in a renovascular model of hypertension

POLIZIO, AH; BALESTRASSE, K; GORNALUSSE, GG; GORZALCZANY, S; SANTA CRUZ, D; YANNARELLI, G; PEÑA, C; TOMARO, ML

REGULATORY PEPTIDES

Elsevier

Año: 2009 vol. 156 p. 28 - 33

0167-0115

<!-- /* Font Definitions */ @font-face {font-family:AdvTT5235d5a9+fb; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> 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 sacri!ced; 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 signi!cantly 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.