title: [Bradykinin attenuates mechanical stress-induced myocardial hypertrophy through inhibiting the Ca²⁺/ calcineurin pathway].
abstract: OBJECTIVE
  To evaluate the inhibitory effect and related mechanism of bradykinin on mechanical stress induced myocardial hypertrophy.
  
  
  METHODS
  Neonatal rat cardiomyocytes were isolated and cultured in silicon plates. All cardiomyocytes were randomly divided into three groups: control group, mechanical stretch group (mechanical stretch of silicon plates to 120% for 30 min) and mechanical stretch plus bradykinin group (1×10(-8) mol/L for 24 h before stretch). The protein synthesis and surface area of cardiomyocytes were detected by [(3)H] leucine incorporation and immunofluorescence of α-MHC, respectively. mRNA expression of atrial natriuretic peptide (ANP) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was detected by real time-PCR, the phosphorylation of calcineurin (CaN), the expression of Angiotensin II receptor 1 (AT1R) and angiotensin converting enzyme (ACE)by Western blot.
  
  
  RESULTS
  The surface area of cardiomyocytes of mechanical stretch group [(973 ± 103) µm(2)] was significantly enlarged than in control group [(312 ± 29) µm(2)] and this effect could be partly attenuated by bradykinin [(603 ± 74) µm(2), all P < 0.05]. Mechanical stretch also significantly increased the protein synthesis, up-regulated the expression of ANP and decreased the expression of SERCA2, and these effects could be partly reversed by pretreatment with bradykinin. Moreover, bradykinin partly abolished the mechanical stretch-induced increases in CaN phosphorylation, up-regulation of AT1R but preserved the expression of ACE.
  
  
  CONCLUSIONS
  Bradykinin significantly attenuates mechanical stretch-induced myocardial hypertrophy through inhibition of Ca(2+)/CaN pathway.
authors.affiliation: Department of Pharmacology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.forename: Guang
authors.initials: G
authors.lastname: DU
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Heng
authors.initials: H
authors.lastname: Zheng
authors.forename: He-Song
authors.initials: HS
authors.lastname: Zeng
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D049108:Cell Enlargement / Q000187:drug effects*; D002478:Cells, Cultured; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013314:Stress, Mechanical
chemical_list: D019703:Calcineurin; D001920:Bradykinin; D002118:Calcium