title: The role of potassium channels in the vasodilatory effect of levosimendan in human internal thoracic arteries.
abstract: OBJECTIVE
  We investigated the role of potassium channels in vasodilatory effect of levosimendan in human internal thoracic arteries.
  
  
  METHODS
  Samples of redundant internal thoracic arteries obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system.
  
  
  RESULTS
  Levosimendan (10(-8)-10(-5) M) or cromakalim (10(-8)-10(-5) M) produced concentration-dependent relaxation responses in human internal thoracic arteries precontracted by 10(-6) M phenylephrine. The relaxant responses to levosimendan did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human internal thoracic artery rings with adenosine 3',5'-triphosphate (ATP)-dependent potassium channel blocker glibenclamide (10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The Ca2+-activated potassium channel blocker iberiotoxin (10(-7) M) also caused a significant but smaller inhibition on relaxant responses to levosimendan. Incubation of the rings with the voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) for 10 min did not cause significant alterations in relaxant responses to levosimendan.
  
  
  CONCLUSIONS
  The findings of this study suggested that levosimendan-induced relaxation responses in human internal thoracic arteries were depended on the activation of ATP-dependent and Ca2+-activated potassium channels.
authors.affiliation: Department of Pharmacology, Akdeniz University, Medical Faculty, 07070 Antalya, Turkey.
authors.forename: Coskun
authors.initials: C
authors.lastname: Usta
authors.forename: Bilsen
authors.initials: B
authors.lastname: Eksert
authors.forename: Ilhan
authors.initials: I
authors.lastname: Gölbasi
authors.forename: Zekiye
authors.initials: Z
authors.lastname: Bigat
authors.forename: Sadi S
authors.initials: SS
authors.lastname: Ozdem
mesh_terms: D000368:Aged; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019806:Cromakalim / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077464:Simendan; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011724:Pyridazines; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D019806:Cromakalim; D010656:Phenylephrine; D000077464:Simendan; D005905:Glyburide