title: Protective effects of low-dose rosuvastatin on isoproterenol-induced chronic heart failure in rats by regulation of DDAH-ADMA-NO pathway.
abstract: OBJECTIVE
  Cardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms.
  
  
  METHODS
  Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection. Simultaneously, low-dose rosuvastatin (5 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by hemodynamic parameter, histopathological variables, serum asymmetric dimethylarginine (ADMA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and myocardial nitric oxide (NO), and the levels of dimethylarginine dimethylaminohydrolase 2 (DDAH2), arginine methyltransferases 1 (PRMT1) and endothelial nitric oxide synthase (eNOS) expression were analyzed.
  
  
  RESULTS
  Therapeutic rosuvastatin (5 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of ventricle, reduced the increased serum content of ADMA, cTnI, and BNP, and elevated myocardial NO in rats (P<.05). Besides, rosuvastatin also significantly inhibited fibrosis of myocardium, normalized the increased PRMT1 and decreased DDAH2 expression.
  
  
  CONCLUSIONS
  Low-dose rosuvastatin exerted cardioprotective effects on isoproterenol-induced heart failure in rats by modulating DDAH-ADMA-NO pathway, and it may present the new therapeutic value in ameliorating chronic heart failure.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Ningxia Medical University, Yinchuan, China.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China.|Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Yehua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005355:Fibrosis; D006333:Heart Failure / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D007545:Isoproterenol; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*; D019210:Troponin I / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D019210:Troponin I; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase; D007545:Isoproterenol
keywords: 
  ADMA
  ; 
  DDAH
  ; 
  NO
  ; Chronic heart failure; Isoproterenol; Rosuvastatin