Effects of a losartan pretreatment in an experimental model of ischemic acute kidney injury

SARA M. MOLINAS; CESAR CORTÉS-GONZÁLEZ; YVETT GONZÁLEZ-BOBADILLA; LILIANA MONASTEROLO; CRISTINO CRUZ; M. MÓNICA ELÍAS; NORMA A. BOBADILLA; LAURA TRUMPER

NEPHRON

Karger AG

Lugar: Basel, Switzerland; Año: 2009 vol. 112 p. 10 - 19

0028-2766

Background/Aims: Contributions in the understanding of acute renal failure (ARF) pathogenesis has not been translated into an effective clinical therapy. We studied the effects of pretreatment with the Angiotensin II type 1 (AT1) receptor blocker, losartan, on renal function, tissue injury, inflammatory response and serum aldosterone levels in a model of ischemic ARF. Methods: Rats underwent unilateral renal ischemia followed by 24 hours of reperfusion (IR), and were pretreated or not with 8 (IRL8) or 80 (IRL80) mg/kg/day of losartan during three days. Results: IR kidneys showed marked renal dysfunction, epithelial damage, capillary congestion, increased myeloperoxidase (MPO) activity and TNF-a, IL1-b and IL-6 mRNA levels. IRL80 kidneys showed protection against dysfunction and tissue injury, associated with normal MPO activity and cytokine mRNA levels. The lower dose was not able to afford the same degree of functional renoprotection and could not prevent the increment in MPO or proinflammatory cytokines mRNA. The high losartan dose completely prevented the increment in serum aldosterone levels induced by IR. Conclusion: Renoprotection of the high losartan dose would be mainly mediated by its antiinflammatory actions. Our results show a potential pathophysiological role of AT1 activation in promoting renal dysfunction, structural injury, inflammation and aldosterone elevation after IR injury.