title: Combination Therapy with Losartan and α-Tocopherol in Acute Ureteral Obstruction-Induced Renal Excretory Dysfunction and Acidification Defect.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Izadpanah
authors.initials: I
authors.lastname: Gheitasi
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Seyed Mostafa
authors.initials: SM
authors.lastname: Moosavi
keywords: Alfa-tocopherol; Losartan; Renal tubular acidosis; Ureteral obstruction