Losartan pretreatment ameliorates renal dysfunction and tissue damage caused by ischemic and ischemic-reperfusion injury

MOLINAS, SARA M.; TONIOLO, M. FERNANDA; TRUMPER, LAURA; MONASTEROLO, LILIANA; ELÍAS, M. MÓNICA

Rio de Janeiro. Brasil

Congreso; World Congress of Nephrology 2007; 2007

International Society of Nephrology

Losartan pretreatment ameliorates renal dysfunction and tissue damage caused by ischemic and ischemic-reperfusion injury Molinas, Sara1; Toniolo, M. Fernanda2; Trumper, Laura3; Monasterolo, Liliana1; Elías, M. Mónica1. Farmacología. Departamento de Ciencias Fisiológicas. Facultad Ciencias Bioquímicas y Farmacéuticas. Universidad Nacional de Rosario, Argentina. 1CONICET. 2Beca Carrillo-Oñativia. 3CIUNR World Congress of Nephrology 2007. Del 21 al 25 de abril de 2007. Rio de Janeiro. Brasil. Renal ischemic-reperfusion injury (IRI) is associated to a serious of complex and interrelated events involving renal vasoconstriction, tubular damage and glomerular injury. Renin-angiotensin system is activated in several renal diseases, including IRI. Angiotensin II (AGII), via AT1 receptor, promotes vasoconstriction, proliferation, inflammation and fibrosis. The role of AT1 in the pathophysiology of renal IRI remains unclear.     The aim of this work was to evaluate the effect of the AT1 receptor antagonist, losartan, on renal dysfunction and tissue damage caused by ischemia and ischemia-reperfusion. Male Wister rats (n=6 per experimental group) were submitted to 40 minutes of unilateral renal ischemia without reperfusion (I) or followed by 24 hours of reperfusion (IR). Another group received losartan (Roemmers, 80 mg/kg/day, i.p.) during 3 days previous to ischemia (IL) or ischemia-reperfusion (IRL). Control animals were submitted to sham operation (C) and another control group was pretreated with losartan (CL). Control and postischemic kidney function were measured by conventional clearance techniques. Renal function parameters were analysed using ANOVA followed by Newman-Keuls contrast. For histological studies, kidneys from all experimental groups were fixed and stained with hematoxylin-eosin and PAS. IR showed marked alterations in hemodynamic and tubular parameters. Losartan pretreatment attenuated this damage. VFG (ml/min.g kidney): C: 1.3±0.2; CL: 1.4±0.2; IR: 0.004±0.001*; IRL: 0.4±0.07*#. EFNa+(%): C: 1.4±0.2; CL: 1.4±0.1; IR: 88±25*; IRL: 3.8±0.9*#, *p<0.05 vs C, #p<0.05 vs IR. Degeneration of tubular structure, loss of brush border, tubular dilatation and vacuolization of cell cytosol were observed in I group. IR group showed extensive tubular necrosis, tubular cast formation, collapse of glomerular tuft, and vacuolization of arteries and arterioles smooth muscle cells. Losartan pretreated animals (IL and IRL) presented less severe morphologic lesions in tubules, glomeruli and vessels. Renal function in CL did not differ from C group. CL showed no morphological alterations. Losartan attenuated renal dysfunction and tissue damage associated to ischemia and ischemia-reperfusion injury, suggesting an important role of AT1 activation in the pathophysiology of renal IRI.