title: Effect of targeting mitogen-activated protein kinase on cardiac remodeling in rats.
abstract: BACKGROUND
  Increasing evidence suggests that the activation of p38 mitogen-activated protein kinase (p38MAPK) plays a role in cardiac remodeling. Targeting p38MAPK using drugs reported to interfere with its phosphorylation, namely statins and all-trans retinoic acid (atRA), might play a role in ameliorating this remodeling.
  
  
  RESULTS
  Cardiac remodeling was induced in male albino rats by chronic inhibition of nitric oxide (NO) synthesis by N-nitro L-arginine methyl ester (L-NAME). Daily oral administration of L-NAME for 4 weeks resulted in the elevation of mean arterial blood pressure (MABP) together with cardiac remodeling evidenced by an increase in left ventricular-body weight ratio together with an increase in cardiac hydroxyproline concentration and a decrease in left ventricular papillary muscle-developed tension. An elevation in cardiac phosphorylated p38MAPK concentration, tumor necrosis factor alpha concentration and in cardiac caspase 3 activity was also observed. Administration of either rosuvastatin or all-trans retinoic acid (atRA), starting 4 weeks after L-NAME administration, ameliorated remodeling and improved all studied parameters.
  
  
  CONCLUSIONS
  Targeting MAPK might represent a useful therapeutic avenue to ameliorate cardiac remodeling and support the notion that atRA and statins are potential candidates for the prevention and therapy of cardiac remodeling.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. mnhbaraka@yahoo.com
authors.forename: Azza
authors.initials: A
authors.lastname: Baraka
authors.forename: Maher
authors.initials: M
authors.lastname: Mikhail
authors.forename: Aida
authors.initials: A
authors.lastname: Guemei
authors.forename: Samar
authors.initials: S
authors.lastname: El Ghotny
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016503:Drug Delivery Systems; D005464:Fluorobenzenes / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D000068718:Rosuvastatin Calcium; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D006909:Hydroxyproline; D019331:NG-Nitroarginine Methyl Ester