The role of potassium channels in the vasodilatory effect of levosimendan in human internal thoracic arteries.
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.
Usta
Coskun
C
Department of Pharmacology, Akdeniz University, Medical Faculty, 07070 Antalya, Turkey.
Eksert
Bilsen
B
Gölbasi
Ilhan
I
Bigat
Zekiye
Z
Ozdem
Sadi S
SS
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*
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