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Yildiz O, Seyrek M, Yildirim V, Demirkilic U, Nacitarhan C: Potassium channel-related relaxation by levosimendan in the human internal mammary artery. Ann Thorac Surg. 2006 May;81(5):1715-9.
BACKGROUND: Levosimendan is a potent inotropic and vasodilator drug used in the treatment of decompensated heart failure. There is no study on in vitro effects of levosimendan in human isolated arteries. METHODS: We investigated the effect of levosimendan on contractile tone of human isolated internal mammary artery (IMA). The responses in IMA were recorded isometrically by a force-displacement transducer in isolated organ baths. Levosimendan was added to organ baths either at rest or after precontraction with phenylephrine (1 micromol/L). Levosimendan-induced relaxations were tested in the presence of cyclooxygenase inhibitor indomethacin (10 micromol/L), nitric oxide synthase inhibitor N122-nitro-L-arginine methyl ester (100 micromol/L), large-conductance calcium-activated potassium-channel inhibitor tetraethylammonium (1 mmol/L), adenosine triphosphate-sensitive potassium-channel inhibitor glibenclamide (10 micromol/L), and voltage-sensitive potassium-channel inhibitor 4-aminopyridine (1 mmol/L). RESULTS: Levosimendan (10 nmol/L to 3 micromol/L) produced potent relaxation in human IMA (maximal effect, 75.3% +/- 4.9% of phenylephrine maximum contraction, 6.8 +/- 0.1, n = 15; -log10 of 50% effective concentration). Vehicle had no significant relaxant effect. The relaxation to levosimendan is not affected by either potassium-channel inhibitors (tetraethylammonium and 4-aminopyridine) or cyclooxygenase and nitric oxide synthase inhibitors. Glibenclamide (10 micromol/L) inhibited levosimendan-induced relaxation significantly (p < 0.01). CONCLUSIONS: Levosimendan effectively and directly decreases the tone of IMA. The mechanism of levosimendan-induced relaxation in IMA appears in part to be adenosine triphosphate-sensitive potassium-channel opening action. Levosimendan may be a cardiovascular protective agent by its relaxing action on the major arterial graft, IMA. |
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