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Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts

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Abstract

Inhibition of endothelin-A (ETA) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study, we investigate the effect of ETA-receptor inhibition on the development of regional alterations of the transient outward K+ current (I to) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague–Dawley rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ETA-receptor antagonist darusentan (LU135252, 35 mg [kg body weight]−1 day−1) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p < 0.001) and caused a significant reduction in I to (at +40 mV) in epicardial myocytes (19.5 ± 1.2 pA pF−1, n = 32 vs 23.2 ± 1.2 pA pF−1, n = 35, p < 0.05). Darusentan further reduced I to in AS (15.4 ± 1.3 pA pF−1, n = 37, p < 0.05) and sham-operated animals (19.8 ± 1.6 pA pF−1, n = 48, ns.). The effects of AS and darusentan on I to were significant and independent as tested by two-way analysis of variance. I to was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude of I to in the epicardial region of the left ventricle but that ETA-receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy.

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Acknowledgments

We are most grateful to Telse Kock for expert technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Institut für Vegetative Physiologie und Pathophysiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Michael Wagner, Diane Goltz, Carolin Stucke, Alexander Peter Schwoerer, Heimo Ehmke & Tilmann Volk

  2. Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstraße 6, 91054, Erlangen, Germany

    Michael Wagner & Tilmann Volk

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  1. Michael Wagner
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  2. Diane Goltz
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  3. Carolin Stucke
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  4. Alexander Peter Schwoerer
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  6. Tilmann Volk
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Correspondence to Tilmann Volk.

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Wagner, M., Goltz, D., Stucke, C. et al. Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts. Pflugers Arch - Eur J Physiol 454, 595–604 (2007). https://doi.org/10.1007/s00424-007-0227-1

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  • DOI: https://doi.org/10.1007/s00424-007-0227-1

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