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Potassium Channels in the Vasodilating Action of Levosimendan on the Human Umbilical Artery

Department of Pharmacology, Ankara, Turkey; Gulhane School of Medicine, Department of Pharmacology, Etlik, 06018, Ankara, Turkey; oyildiz{at}gata.edu.tr

Cahit Nacitarhan, MD,PhD

Melik Seyrek, MD

Department of Pharmacology, Ankara, Turkey

Objective: Levosimendan is a calcium-sensitizing agent and indoilator 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 µM). Levosimendan-induced relaxations were tested in the presence of the large conductive Ca²⁺-activated K⁺ channel inhibitor tetraethylammonium (TEA, 1 mM), the adenosine triphosphate (ATP)-sensitive K⁺ channel inhibitor glibenclamide (GLI, 10 µM), 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 µM) and the nitric oxide synthase inhibitor L-NAME (100 µM).

Results: Levosimendan (10 nM to 3 µM) produced potent relaxation in the HUA. Vehicle had no significant relaxant effect. The relaxation of 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).

Conclusion: These results show that levosimendan effectively and directly decreases the tone of the HUA. The mechanism of this levosimendan-relaxation in the HUA appears in part to be due to voltage-gated and large conductance Ca²⁺-activated K⁺ channel opening action.

Key Words: Human umbilical artery • levosimendan • potassium channels • smooth muscle

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 4, 312-315 (2006)
DOI: 10.1016/j.jsgi.2006.02.005


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