title: Effect of aliskiren and carvedilol on expression of Ca(2+)/calmodulin-dependent protein kinase II δ-subunit isoforms in cardiac hypertrophy rat model.
abstract: BACKGROUND
  The critical role of CaMKIIδ isoforms in cardiac hypertrophy is well documented.
  
  
  OBJECTIVE
  This study was aimed to investigate the possible inhibitory effects of aliskiren (ALS) and/or carvedilol (CAV) on CaMKIIδ isoforms expression in experimental cardiac hypertrophy.
  
  
  METHODS
  Male Wistar albino rats were subcutaneously injected with isoproterenol (ISO) (5 mg/kg/day) for 4 weeks to induce cardiac hypertrophy. Hypertrophied rats were daily treated with either ALS (10 mg/kg) and/or CAV (10 mg/kg). At the end of the treatment, rats were killed; blood and hearts were collected for assessing different biochemical parameters.
  
  
  RESULTS
  ISO treatment significantly increased heart weight to body weight (HW/BW) ratio, serum creatine kinase MB (CK-MB) and troponin T (Tn-T) levels, and plasma renin activity (PRA) as compared to control rats. Additionally, ISO treatment produced a significant increase in the expression of myocardial CaMKIIδ2 and CaMKIIδ3 that were associated with significant elevation in myocardial caspase-3 protein expression. Histopathological examination of rats exposed to ISO treatment showed severe myocardial cell degeneration. ALS and/or CAV treatment significantly reduced the altered HW/BW ratio, serum CK-MB and Tn-T levels, PRA, and caspase-3 protein expression in hypertrophied rats, with maximal improvement in the combination group. These biochemical findings were supported by the histopathological examination of the heart tissue. Additionally, treatment with ALS and CAV significantly inhibited ISO-induced increase in CaMKIIδ2 and CaMKIIδ3 expression levels.
  
  
  CONCLUSIONS
  The present study indicated that ALS and CAV treatment ameliorated ISO-induced hypertrophy via inhibiting the expression and the activity of CaMKIIδ isoforms and the associated myocardial apoptosis.
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors.forename: Anfal Fahad
authors.initials: AF
authors.lastname: Bin-Dayel
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Saudi Arabia .|b Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University , Cairo , Egypt .
authors.forename: Nayira A
authors.initials: NA
authors.lastname: Abdel Baky
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors.forename: L M
authors.initials: LM
authors.lastname: Fadda
authors.affiliation: c Anatomy Department, Faculty of Medicine, King Saud University , Riyadh , Saudi Arabia , and.
authors.forename: Raeesa A
authors.initials: RA
authors.lastname: Mohammad
authors.affiliation: d Department of Cell Biology , King Faisal Specialist Hospital & Research Centre , Riyadh , Saudi Arabia.
authors.forename: Futwan
authors.initials: F
authors.lastname: Al-Mohanna
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D000077261:Carvedilol; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000008:administration & dosage / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D020033:Protein Isoforms; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D020107:Troponin T / Q000097:blood
chemical_list: D000577:Amides; D002227:Carbazoles; D005650:Fumarates; D011412:Propanolamines; D020033:Protein Isoforms; D020107:Troponin T; D000077261:Carvedilol; C446481:aliskiren; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D052279:Creatine Kinase, MB Form; D012083:Renin; D007545:Isoproterenol
keywords: Aliskiren; CaMKIIδ-isoforms; cardiac hypertrophy; carvedilol; caspase-3