Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein

János Pataricza, József Hõhn, András Petri, Ádám Balogh, Julius Gy Papp

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Abstract

In the present study the vasorelaxing capacity of cromakalim, an ATP-sensitive potassium-channel (K(ATP) channel) activator, and that of levosimendan, a new positive inotropic and vasodilating drug with calcium sensitizing and potassium-channel-activating properties, were compared in human isolated portal vein. Based on the 50% effective concentrations (EC50), levosimendan was found to be about 16-fold more potent (EC50=0.281±0.03 μM) as a relaxing agent than cromakalim (EC50=4.53±0.12 μM) in noradrenaline-precontracted portal venous preparations. Glibenclamide, the known inhibitor of K(ATP) channels, was able to prevent the cromakalim-induced venodilation completely. Glibenclamide (15 μM) decreased the quasi-maximal effect of levosimendan (at 1.27 μM by about 60%) and also the effects of those submicromolar concentrations of the inodilator (at 0.1 μM by 23%, at 0.3 μM by 27% and at 0.7 μM by 19%, on average) which were therapeutically effective in preliminary human studies. These findings indicate that, in the human portal vein, both cromakalim and levosimendan are powerful vasorelaxants and that a considerable part of the relaxing effect induced by levosimendan is of cromakalim type.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalJournal of Pharmacy and Pharmacology
Volume52
Issue number2
DOIs
Publication statusPublished - Feb 2000

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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