title: The Effect of Combined Treatment with the (Pro)Renin Receptor Blocker HRP and Quinapril in Type 1 Diabetic Rats.
abstract: OBJECTIVE
  Diabetic nephropathy remains a major clinical problem. The effects of prorenin might be adverse, but the literature data are controversial. We compared the renal effects of the (pro)renin receptor ((P)RR) blockade and angiotensin converting enzyme (ACE) inhibition on the progression of diabetic nephropathy in rats.
  
  
  METHODS
  Diabetes (DM) was induced by ip. streptozotocin administration in adult male Sprague-Dawley rats, followed by eight weeks of treatment with the (P)RR blocker "handle region" decoy peptide (HRP, 0,1 mg/kg/day) or with the ACE inhibitor Quinapril (Q, 50 mg/kg/day) and grouped as follows: 1. Control (n=10); 2. DM (n=8); 3. DM+HRP (n=6); 4. DM+Q (n=10); 5. DM+Q+HRP (n=10). Renal functional parameters, histology and gene expressions were evaluated.
  
  
  RESULTS
  HRP reduced glomerulosclerosis and podocyte desmin expression, but did not affect proteinuria and tubular ERK(1/2) phosphorylation. Both Q and Q+HRP treatment reduced proteinuria, glomerular and tubular damage, tubular TGF-ß1 expression and ERK(1/2) phosphorylation to the same extent.
  
  
  CONCLUSIONS
  The effects of HRP were partially beneficial on diabetic kidney lesions as HRP reduced damage but did not improve tubular damage and failed to reduce ERK(1/2) phosphorylation in rats. The combination of HRP with Quinapril had no additive effects over Quinapril monotherapy on the progression of diabetic nephropathy.
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Budapest, Hungary.|International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Kökény
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Budapest, Hungary.
authors.forename: Lilla
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Révész
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Budapest, Hungary.|International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós M
authors.initials: MM
authors.lastname: Mózes
authors.affiliation: 2nd Department of Internal Medicine, St. Stephen Hospital, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Vörös
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Budapest, Hungary.|International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szénási
authors.affiliation: Department of Pathophysiology, Semmelweis University, Budapest, Budapest, Hungary.|International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Rosivall
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000494:pharmacology / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D044005:Tetrahydroisoquinolines; D012083:Renin; D000077583:Quinapril
keywords: (pro)Renin receptor; ACE inhibitor; Decoy peptide; Diabetic nephropathy; Podocyte