This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Yildiz, O. Articles by Seyrek, M. Search for Related Content PubMed PubMed Citation Articles by Yildiz, O. Articles by Nacitarhan, C. Articles by Seyrek, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                         What's this?

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


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?