title: [Bradykinin B1 receptor antagonist reduces the antiproliferative effects of captopril on cardiac fibroblasts in neonatal rats].
abstract: OBJECTIVE
  To investigate the role and mechanism of the bradykinin(BK) B1 receptor in the antiproliferative effects of the angiotensin-converting enzyme inhibitor (ACEI) captopril on rat cardiac fibroblasts (CFs) treated with angiotensin II (Ang II).
  
  
  METHODS
  Neonatal rat cardiac fibroblasts were randomly treated with Ang II, captopril, B2 receptor antagonist (icatibant) or B1 receptor antagonist (des-Arg10, Leu9-kallidin). Thiazolyl blue (MTT) and flow cytometry (FCM) were used to evaluate cell number and cell cycle, respectively. Nitric oxide (NO) and intracellular cGMP level were measured by colorimetry and radioimmunoassay.
  
  
  RESULTS
  After incubating the fibroblasts with 10(-7) mol/L Ang II for 48 hours, the percentage of CFs in the S stage and the value of MTT A490 nm were significantly increased (P < 0.01 vs control), and this increase was inhibited by 10(-5) mol/L captopril; however, NO and cGMP level were significantly higher than with Ang II alone (P < 0.01). 10(-5) mol/L icatibant attenuated the effects of captopril, which were blunted further by dual blockade of both B1 and B12.
  
  
  CONCLUSIONS
  Acting via the B2 receptor, BK contributes to the antiproliferative effects of ACEI on CFs. In the absence of the B2 receptor, the B1 receptor may assume some of the functions of the B2 receptor and contribute to inhibition of CFs proliferation by ACEI.
authors.affiliation: Department of Geriatric Research, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.forename: Jiang
authors.initials: J
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
mesh_terms: D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D006352:Heart Ventricles; D032383:Myocytes, Cardiac / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D002216:Captopril