title: Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats.
abstract: OBJECTIVE
  This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats.
  
  
  METHODS
  Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (dp/dt (max)), rate of left ventricular pressure decay (dp/dt (min)) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff's heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer.
  
  
  RESULTS
  The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, dp/dt (max), dp/dt (min) and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment.
  
  
  CONCLUSIONS
  AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.
authors.affiliation: ISF College of Pharmacy, Moga, India.
authors.forename: Kulwinder
authors.initials: K
authors.lastname: Singh
authors.forename: Kuldeepak
authors.initials: K
authors.lastname: Sharma
authors.forename: Manjeet
authors.initials: M
authors.lastname: Singh
authors.forename: P L
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003971:Diastole / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D010455:Peptides; D011507:Proteinuria / Q000097:blood / Q000150:complications / Q000503:physiopathology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: C469726:AVE 0991; D001786:Blood Glucose; D002316:Cardiotonic Agents; D007093:Imidazoles; D008055:Lipids; D010455:Peptides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D003404:Creatinine