combination therapy with losartan and α-tocopherol in acute ureteral obstruction-induced renal excretory dysfunction and acidification defect

background: previous study by the authors showed that a-tocopherol prevents oxidative stress but would not improve depressed excretory variables in post-obstructed kidney (pok) after release of 24-h unilateral ureteral obstruction (uuo). this study is a supplementary investigation on the effects of a-tocopherol combined with an antagonist of angiotensin-ii type-1 (at1) receptor on renal dysfunction following release of acute uuo. methods: the left ureter was ligated in different groups of male sprague-dawley rats that received normal saline, losartan or losartan/a-tocopherol (n=6 in each group). after releasing 24-h uuo, urine of each kidney was separately collected under paraffin during 1-3 h of post-release period and then both kidneys were removed for measuring malondialdehyde (mda) and ferric reducing/antioxidant power (frap). results: losartan-treatment decreased mda and increased frap, creatinine-clearance and sodium-reabsorption in pok, while co-treatment with losartan and a-tocopherol not only augmented improvement in these variables but also elevated potassium-excretion, free-water reabsorption and urine-osmolality. however, uuo-induced fall in urinary pco2 and rise in ph and bicarbonate-excretion of pok were ameliorated equally with losartan and losartan/a-tocopherol. conclusion: activation of at1-receptor contributes to the development of renal distal acidification defect induced by acute ureteral obstruction. the co-treatment with losartan and a-tocopherol showed that their effects on preventing oxidative stress along with ameliorating glomerular filtration and tubular fluid-delivery in pok could lead to improvement in tubular transport of sodium and potassium as well as urine-concentrating ability at the early post-release period.