title: Protection of renal impairment by angiotensin II type 1 receptor blocker in rats with post-infarction heart failure.
abstract: Renal impairment is a frequent accompaniment post-myocardial infarction (MI) heart failure. However, the mechanisms and predictors are yet poorly understood. The present study aimed to explore early markers for renal impairment and to test the hypothesis that angiotensin II type 1 receptor (AT1R) blocker exerted renoprotection by regulating local angiotensin II receptors post-MI heart failure. Sprague-Dawley rats underwent ligation of the left descending coronary artery and were treated with losartan (20 mg/kg/day) or vehicle for 3 or 9 weeks. Samples of urine, blood, and kidney were collected for assessment of renal function, histology, and protein changes. The current study revealed that blood cystatin C, rather than serum creatinine and blood urea nitrogen, as well as urine proteins, increased post-MI heart failure significantly. These changes were associated with increased immunohistochemical staining of AT1R and AT2R proteins, accompanied by increased renal fibrosis, tubular necrosis, and inflammatory cell infiltration. Treatment with losartan for MI rats significantly attenuated upregulated AT1R but not AT2R. Losartan also decreased blood cystatin C levels and attenuated renal fibrosis, tubular necrosis, and inflammatory cell infiltration. In conclusion, blood cystatin C may be a better marker for early renal impairment. AT1R blockers modulated local angiotensin II receptors, as well as inflammatory reaction and profibrotic effects, providing potential clinical application in the setting of cardiorenal syndrome post-MI.
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhuzhi
authors.initials: Z
authors.lastname: Wen
authors.forename: Muyan
authors.initials: M
authors.lastname: Cai
authors.forename: Zun
authors.initials: Z
authors.lastname: Mai
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Chen
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Geng
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan