Effect of Targeting Mitogen-Activated Protein Kinase on Cardiac Remodeling in Rats

• Published in: Journal of cardiovascular pharmacology and therapeutics 2009-12, Vol.14 (4), p.339-346
• Main Authors: Baraka, Azza, Mikhail, Maher, Guemei, Aida, El Ghotny, Samar
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - drug effects; Caspase 3 - metabolism; Drug Delivery Systems; Fluorobenzenes - pharmacology; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - pathology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxyproline - metabolism; Male; Myocardium - metabolism; NG-Nitroarginine Methyl Ester - antagonists & inhibitors; NG-Nitroarginine Methyl Ester - pharmacology; p38 Mitogen-Activated Protein Kinases - metabolism; Papillary Muscles - drug effects; Pyrimidines - pharmacology; Random Allocation; Rats; Rosuvastatin Calcium; Sulfonamides - pharmacology; Tretinoin - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Ventricular Remodeling - drug effects
• ISSN: 1074-2484; 1940-4034
• DOI: 10.1177/1074248409349620

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. Methods and 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.