title: Effects of carvedilol alone and in the presence of cyclosporine A on the DNA synthesis of cultured vascular smooth muscle cells.
abstract: OBJECTIVE
  There is still no reliable method of preventing or treating chronic rejection or transplant vascular sclerosis. A recent in vitro cell culture study showed that carvedilol significantly inhibited the proliferation of vascular smooth muscle cells (VSMCs); however, the effect of carvedilol in the presence of cyclosporine (CsA) has not yet been reported. Using in vitro cultured VSMCs, we measured the antiproliferative activity of carvedilol alone and in combination with CsA.
  
  
  METHODS
  Growth-arrested cultured VSMCs from the thoracic aorta of Sprague-Dawley rats were exposed to platelet-derived growth factor (PDGF)-BB, endothelin (ET)-I, and angiotensin (ANG)-II. Carvedilol (1 and 10 microM) and/or CsA (100 nM) were added as test drugs. DNA synthesis was assessed by measuring the incorporated [3H]thymidine activity, and the percentage of inhibition in the presence of the test drugs was determined.
  
  
  RESULTS
  Compared with the PDGF-stimulated control, DNA synthesis decreased significantly to 60.3% +/- 10.4% and 18.3% +/- 5.9% in the presence of 1 and 10 microM of carvedilol, respectively (P < 0.05, each). Carvedilol significantly inhibited the activity of VSMCs stimulated by ET-1 and ANG-II. The IC50 of carvedilol was 1-10 microM. CsA only inhibited VSMCs significantly in the PDGF-stimulated subgroup. The addition of CsA in the presence of carvedilol did not affect the inhibitory activity of carvedilol. The pattern of inhibition in the combined group was uniform and similar to that of the carvedilol alone group, regardless of the stimulator used.
  
  
  CONCLUSIONS
  Carvedilol significantly inhibited the DNA synthesis of VSMCs regardless of the kind of stimulators examined, even in the presence of CsA. These results indicate that carvedilol has the unique potential to inhibit the development of transplant vascular sclerosis in hypertensive transplant recipients under CsA-based immunosuppression.
authors: Department of Surgery, Yonsei University, Seoul, South Korea.
authors: Yu Seun
authors: YS
authors: Kim
authors: Myoung Soo
authors: MS
authors: Ki
authors: Hunjoo
authors: H
authors: Ha
authors: Jehyun
authors: J
authors: Park
authors: Hae Jin
authors: HJ
authors: Kim
authors: Kiil
authors: K
authors: Park
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D007166:Immunosuppressive Agents; D011412:Propanolamines; D000077261:Carvedilol; D016572:Cyclosporine; D004247:DNA