title: [Effect of cyclosporine A on myocardial calcineurin activity of the right ventricle and plasma NO, nitric oxide synthase and endothelin-1 levels in rats with chronic hypoxia].
abstract: OBJECTIVE
  To study the role of calcineurin in the progression of right ventricle myocardial hypertrophy in rats exposed to chronic hypoxia by examining the effect of Ca(2+) channel blockers on the activation of calcineurin and plasma levels of nitric oxide (NO), NO synthase, and endothelin-1 (ET-1).
  
  
  METHODS
  Rat models of right ventricle myocardial hypertrophy were established by exposing the rats to chronic hypoxia in 10.0%+/-0.5% O(2) for 7 d. The 24 rat models were assigned into normoxic group, hypoxic group and cyclosporin A (CsA)-treated hypoxic group. The rats in normoxic group were kept under normoxic environment, while those in the other 2 groups were subjected to further hypoxic treatment for 14 d, with the rats in CsA group receiving intraperitoneal CsA injection at 20 mg/kg on a daily basis. On day 21 of the experiment, all the rats were killed to collect the hearts for measuring the weight ratio of the right ventricle to the left ventricle and interventricular septum [RV/  LV+S  ], as well as the right ventricle to body weight ratio (RV/BW); blood samples were also drawn from the ventricles for measuring plasma NO, iNOS, and ET-1 levels, with the ventricular myocardial [Ca(2+)](i) and the activity of calcineurin also determined.
  
  
  RESULTS
  The RV/(LV+S) and RV/BW were significantly higher in hypoxic group than those of the normoxic and CsA groups (P<0.01); the right ventricular myocardial [Ca(2+)](i) in CsA group was significantly higher than that in the other two groups (P<0.01). In comparison with the normoxic group, the right ventricular myocardial calcineurin activity was significantly increased in the hypoxic group. CsA treatment significantly suppressed calcineurin activity (P<0.01).
  
  
  CONCLUSIONS
  Calcineurin possibly plays a role in the progression of right ventricle myocardial hypertrophy in rats with chronic hypoxia. Blocking L-type Ca(2+) channels with CsA effectively prevents the development of myocardial hypertrophy possibly by inhibiting calcium influx and suppressing calcineurin activity.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524023, China. isaac_t@gdmc.edu.cn
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Tan
authors.forename: Chen-zhou
authors.initials: CZ
authors.lastname: Liu
authors.forename: Yu-li
authors.initials: YL
authors.lastname: Jie
authors.forename: You
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu-ge
authors.initials: YG
authors.lastname: Huang
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000032:analysis*; D002908:Chronic Disease; D016572:Cyclosporine / Q000494:pharmacology*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000097:blood*; D051381:Rats
chemical_list: D019332:Endothelin-1; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D019001:Nitric Oxide Synthase; D019703:Calcineurin