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Cilostamide potentiates more the positive inotropic effects of (−)-adrenaline through β2-adrenoceptors than the effects of (−)-noradrenaline through β1-adrenoceptors in human atrial myocardium

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Abstract

Activation of both β1- and β2-adrenoceptors increases the contractility of human atrial myocardium through cyclic AMP-dependent pathways. Cyclic AMP is hydrolised by phosphodiesterases, but little is known about which isoenzymes catalyse inotropically relevant cyclic AMP accumulated upon stimulation of β-adrenoceptor subtypes. We have compared the positive inotropic effects of (−)-noradrenaline and (−)-adrenaline, mediated through β1- and β2-adrenoceptors, respectively, in the absence and presence of the PDE3 inhibitor cilostamide (300 nM) or PDE4 inhibitor rolipram (1 μM) on human atrial trabeculae from non-failing hearts. Cilostamide, but not rolipram, potentiated the effects of both (−)-noradrenaline and (−)-adrenaline. Cilostamide increased the −logEC50M of (−)-adrenaline more than of (−)-noradrenaline (P < 0.05), regardless of whether or not the patients had been chronically treated with β-blockers. The results are consistent with a greater PDE3-catalysed hydrolysis of inotropically relevant cyclic AMP produced through β2-adrenoceptors than β1-adrenoceptors in human atrium.

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Acknowledgement

We are grateful to Romy Kempe for excellent technical assistance.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany

    T. Christ, A. Engel & U. Ravens

  2. Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK

    A. J. Kaumann

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  1. T. Christ
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  2. A. Engel
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  3. U. Ravens
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  4. A. J. Kaumann
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Correspondence to A. J. Kaumann.

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Christ, T., Engel, A., Ravens, U. et al. Cilostamide potentiates more the positive inotropic effects of (−)-adrenaline through β2-adrenoceptors than the effects of (−)-noradrenaline through β1-adrenoceptors in human atrial myocardium. Naunyn-Schmied Arch Pharmacol 374, 249–253 (2006). https://doi.org/10.1007/s00210-006-0119-5

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  • DOI: https://doi.org/10.1007/s00210-006-0119-5

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