Potassium channels in the vasodilating action of levosimendan on the human umbilical artery.
OBJECTIVE
Levosimendan is a calcium-sensitizing agent and inodilator working via potassium channels, which is under current investigation in the treatment of heart failure. We investigated the type of potassium channels that play a role on the dilatating effect of levosimendan on the contractile tones of the isolated human umbilical artery (HUA).


METHODS
The response in the HUA was recorded isometrically by a force displacement transducer in isolated organ baths. Levosimendan was added to organ baths after precontraction with serotonin (5-HT, 1 microM). Levosimendan-induced relaxations were tested in the presence of the large conductance Ca2+-activated K+ channel inhibitor tetraethylammonium (TEA, 1 mM), the adenosine triphosphate (ATP)-sensitive K+ channel inhibitor glibenclamide (GLI, 10 microM), and the voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM). All experiments were performed in solutions containing the cyclooxygenase inhibitor indomethacin (10 microM) and the nitric oxide synthase inhibitor L-NAME (100 microM).


RESULTS
Levosimendan (10 nM to 3 microM) produced potent relaxation in the HUA. Vehicle had no significant relaxant effect. The relaxation to levosimendan was not affected by the K+ channel inhibitor, GLI. However, 4-AP (1 mM) and TEA (1 mM) inhibited levosimendan-induced relaxation significantly (P <.05).


CONCLUSIONS
These results show that levosimendan effectively and directly decreases the tone of the HUA. The mechanism of this levosimendan-induced relaxation in the HUA appears in part to be due to voltage-gated and large conductance Ca2+-activated K+ channel opening action.
Yildiz
Oguzhan
O
Nacitarhan
Cahit
C
Seyrek
Melik
M
D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000098:blood supply; D021041:Placental Circulation / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D002316:Cardiotonic Agents; D006835:Hydrazones; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D011724:Pyridazines; D000077464:Simendan