BACKGROUND AND OBJECTIVE: The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by @entity205 ( @entity870 ) indicates that @entity1369 plays a key role in chronic @entity870 nephrotoxicity. We and other researchers have reported local renal @entity1369 synthesis. To investigate local renal @entity1369 's role in chronic @entity870 nephrotoxicity, we evaluated the effect of @entity14292 (Epl) on @entity8 in adrenalectomized (ADX) @entity35 , and assessed whether the therapeutic benefit was associated with reduction of @entity1810 ( @entity1810 ), @entity2528 ( @entity2528 ), @entity9378 ( @entity9378 ) and collagen I (COL-I) expression. METHODS: Male @entity35 fed a normal- @entity1372 diet were divided in four groups: sham-ADX, ADX, @entity870 , or Epl. @entity35 in the ADX, @entity870 and Epl groups were adrenalectomized first. @entity1369 , @entity1372 and @entity972 levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), @entity870 (25mg/kg/d), or @entity870 and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, @entity1011 clearance (Ccr), @entity82 ( @entity82 ), @entity1369 level in kidney, and renal @entity1369 synthase @entity19320 , COL-I, @entity1810 , @entity2528 and @entity9378 gene expression levels were determined. RESULTS: On the second day after surgery, adrenalectomized @entity35 showed undetectable @entity1369 with natriuresis, @entity2753 , decreased urinary @entity972 excretion and @entity4144 . @entity870 reduced Ccr, induced urinary proteins and up-regulated COL-I, @entity1810 , @entity2528 and @entity9378 gene expression with a significant development of @entity82 . @entity14292 administration prevented @entity82 and COL-I, @entity1810 and @entity9378 up-regulation but did not improve renal function. CONCLUSION: Our results suggest local renal @entity1369 is an important mediator of @entity8 induced by @entity870 .

Inhibition of local @entity1369 by @entity14292 reduces XXXX in a novel model of chronic @entity205 nephrotoxicity.

@entity8 :: ('MESH:D007674', 'Disease') :: ['renal structural damage and renal dysfunction', 'renal injury'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium'] @entity1369 :: ('MESH:D000450', 'Chemical') :: ['Aldosterone', 'aldosterone'] @entity82 :: ('MESH:D005355', 'Disease') :: ['tubulointerstitial fibrosis', 'TIF'] @entity870 :: ('CHEBI:55379', 'Chemical') :: ['CsA'] @entity14292 :: ('MESH:C414690', 'Chemical') :: ['eplerenone', 'Eplerenone'] @entity9378 :: ('29366(Tax:10116)', 'Gene') :: ['PAI-1', 'plasminogen activator inhibitor type 1'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporine A'] @entity1810 :: ('59086(Tax:10116)', 'Gene') :: ['TGF-b1', 'transforming growth factor-b1'] @entity2528 :: ('64032(Tax:10116)', 'Gene') :: ['CTGF', 'connective tissue growth factor'] @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats', 'Rats', 'rats'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity19320 :: ('24294(Tax:10116)', 'Gene') :: ['CYP11B2'] @entity2753 :: ('MESH:D007010', 'Disease') :: ['hyponatremia'] @entity4144 :: ('MESH:D006947', 'Disease') :: ['hyperpotassemia']
@entity8 :: (MESH:D007674,Disease) :: ['renal structural damage']
