title: Attenuation of monocrotaline-induced pulmonary arterial hypertension in rats by rosuvastatin.
abstract: BACKGROUND
  Although the effects of statins on pulmonary arterial hypertension (PAH) have been studied previously, the results remain uncertain.
  
  
  OBJECTIVE
  The aim of this study was to confirm the impacts of rosuvastatin on monocrotaline (MCT)-induced PAH and potential mechanisms.
  
  
  METHODS
  Rats were subjected to a single subcutaneous injection of MCT to induce PAH. In the prevention protocol, the rats received different doses of rosuvastatin (2 and 10 mg·kg·d) for 4 weeks since MCT injection, whereas in the treatment protocol, the rats received different doses of rosuvastatin 4 weeks after MCT injection for 4 weeks. At the end of the studies, hemodynamic parameters were measured, and the morphology of small pulmonary arteries (SPAs) and right ventricular hypertrophy were assessed. The expression of proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase (eNOS) in SPAs, and Rho kinase 1 (ROCK-1) and eNOS in lung tissue were determined.
  
  
  RESULTS
  Rosuvastatin administration could significantly lower mean pulmonary arterial pressure in both prevention and treatment protocols (P < 0.01, respectively), improve survival after PAH development (P < 0.05), and reduce wall thickening of SPAs and right ventricular hypertrophy (P < 0.01, respectively). At the molecular level, rosuvastatin could inhibit the expression of ROCK-1 (P < 0.05, respectively) and PCNA (P < 0.01, respectively) but restore the expression of eNOS (P < 0.05, respectively). These effects were found in a dose-dependent manner.
  
  
  CONCLUSIONS
  The present data confirmed and extended the previous data regarding the protective impacts of statins on PAH. The effects of rosuvastatin seemed to be associated with the regulation of ROCK-1, PCNA, and eNOS expression.
authors.affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Beijing 100037, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Li
authors.forename: Rui-Jin
authors.initials: RJ
authors.lastname: Guan
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D065627:Familial Primary Pulmonary Hypertension; D005464:Fluorobenzenes / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D016686:Monocrotaline; D000068718:Rosuvastatin Calcium; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D054460:rho-Associated Kinases