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Inotropic effects of l-lysine in the mammalian heart

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Abstract

We studied the effects of l-lysine in cardiac preparations of mice and men. Of note, l-lysine increased force of contraction in a concentration- and time-dependent manner in isolated electrically paced left atrium of mouse and in human right atrium. It further increased heart rate and left ventricular pressure in the isolated perfused mouse heart. In isolated adult mouse cardiomyocytes, the contractility as assessed by edge detection was increased as well as the Ca2+ transients after electrically pacing by field stimulation. However, using the patch clamp technique, no effect of l-lysine on action potential duration from a constant holding potential or on current through l-type calcium channels could be observed. However, l-lysine led to a depolarization of unclamped cells. Furthermore, effects of l-lysine were stereospecific, as they were not elicited by d-lysine. The inotropic effects of l-lysine were not abrogated by additionally applied l-ornithine or l-arginine (known inhibitors of lysine transport). However, l-lysine (5 mM) shifted the concentration–response curve for a positive inotropic effect of 5-hydroxytryptamine (5-HT; serotonin) in atrium of transgenic mice (with cardiac specific overexpression of 5-HT4 receptors) to higher concentrations. In summary, we describe a novel positive inotropic effect of an essential amino acid, l-lysine, in the mammalian heart. One might speculate that l-lysine treatment under certain conditions could sustain cardiac performance. Moreover, l-lysine is able to block, at least in part, cardiac 5-HT4 receptors.

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Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (DFG). The technical assistance of C. Geisler and S. Reber is greatly appreciated.

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Str. 4, 06112, Halle, Germany

    Andreas Boldt, Ulrich Gergs, Julia Frenker & Joachim Neumann

  2. Klinik für Herz und Thoraxchirurgie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097, Halle, Germany

    Andreas Simm & Rolf-Edgar Silber

  3. Julius-Bernstein-Institut für Physiologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06112, Halle, Germany

    Udo Klöckner

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  1. Andreas Boldt
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  2. Ulrich Gergs
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  3. Julia Frenker
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  4. Andreas Simm
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  6. Udo Klöckner
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  7. Joachim Neumann
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Correspondence to Joachim Neumann.

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Boldt, A., Gergs, U., Frenker, J. et al. Inotropic effects of l-lysine in the mammalian heart. Naunyn-Schmied Arch Pharmacol 380, 293–301 (2009). https://doi.org/10.1007/s00210-009-0439-3

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  • DOI: https://doi.org/10.1007/s00210-009-0439-3

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