title: Cardiorenal protection in experimental hypertension with renal failure: comparison between vasopeptidase inhibition and angiotensin receptor blockade.
abstract: OBJECTIVE
  The aim of the present study was to compare the preventive impact of treatment with a vasopeptidase inhibitor (VPI) with an angiotensin-receptor blocker (ARB) on left ventricular (LV) function and renal damage in rats with renal failure after 5/6 renal ablation (Nx).
  
  
  METHODS
  Rats (n = 15-20, each group) underwent either sham-operation (Sham) or 5/6 renal ablation (Nx). Two additional groups of Nx-animals (groups Nx-VPI and Nx-ARB) were treated with the VPI ilepatril (AVE7688, 30 mg kg(-1) d(-1)) or with the ARB olmesartan (10 mg kg(-1 )d(-1)). Animals were followed for 4 weeks.
  
  
  RESULTS
  Systolic blood pressure (SBP), LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) were increased 4 weeks after Nx (p < 0.05). LV pressure rise (+dP/dt/LVPmax), LV pressure fall (-dP/dt/LVPmax), and creatinine clearance decreased, while albuminuria and renal glomerulosclerosis index (GSI) increased with Nx (p < 0.05, respectively). In comparison to Nx, treatment with both VPI and ARB normalized SBP, LVH, LVEDP, +dP/dt/LVPmax, and -dP/dt/LVPmax to Sham control levels. GSI, but not creatinine clearance, was also normalized in response to both treatments. The significant increase in albuminuria observed in Nx (+230-fold versus Sham, p < 0.0001) was partially reduced in Nx-VPI (+47-fold versus Sham, p < 0.0001) and fully abolished in Nx-ARB.
  
  
  CONCLUSIONS
  Both ilepatril and olmesartan conferred strong cardiorenal protective effects in rats with renal failure. While cardioprotection was clearly comparable with both treatment regimens, the ARB provided a better protection against the increase in albuminuria, although renal function and structural kidney changes were similarly affected by the VIP and ARB.
authors.affiliation: Institut für Klinische Pharmakologie und Toxikologie, Charité - Universitätsmedizin Berlin , Campus Mitte, Berlin , Germany and.
authors.forename: Fabian
authors.initials: F
authors.lastname: Halleck
authors.forename: Katharina
authors.initials: K
authors.lastname: Schröder
authors.forename: Sven
authors.initials: S
authors.lastname: Holleck-Weithmann
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Lars
authors.initials: L
authors.lastname: Rothermund
mesh_terms: D000419:Albuminuria / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C437965:olmesartan
keywords: Arterial hypertension; cardio-renal syndrome; left ventricular function; renal failure; vasopeptidase inhibition