Potassium Channels in the Vasodilating Action of Levosimendan on the Human Umbilical Artery
Journal of the Society for Gynecologic Investigation, cilt.13, sa.4, ss.312-315, 2006 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 13 Sayı: 4
- Basım Tarihi: 2006
- Doi Numarası: 10.1016/j.jsgi.2006.02.005
- Dergi Adı: Journal of the Society for Gynecologic Investigation
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.312-315
- Anahtar Kelimeler: human umbilical artery, levosimendan, potassium channels, smooth muscle
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
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 μM). 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 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 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). Conclusion: 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. © 2006 Society for Gynecologic Investigation.