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Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium

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Summary

The receptor systems through which serotonin (5-HT), histamine, angiotensin II and endothelin increase the force of contraction were studied in isolated right atria from patients without apparent heart failure.

All agonists increased the atrial force of contraction in a concentration-dependent manner; maximal effects, however, were significantly less than those evoked by isoprenaline or Ca2+. 5-HT and histamine, but not angiotensin II and endothelin, activated adenylate cyclase, whereas endothelin and angiotensin II stimulated inositol phosphate generation. Experiments with subtype-selective antagonists revealed that histamine effects were mediated by H2-receptors (sensitive to ranitidine), 5-HT-effects by 5-HT4-receptors (sensitive to SDZ 205-557) and angiotensin II effects by AT1-receptors (sensitive to losartan).

We conclude that in human right atria the force of contraction can be increased by cyclic AMP-dependent (histamine, 5-HT) and -independent (angiotensin II, endothelin) pathways. Compared to β-adrenoceptors, however, all other receptor systems increase the force of contraction only submaximally indicating that the β-adrenoceptor pathway is the most important physiological mechanism to regulate force of contraction and/or heart rate in the human heart.

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Authors and Affiliations

  1. Abteilung Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen, Hufelandstrasse 55, W-4300, Essen 1, Federal Republic of Germany

    Hans-Reinhard Zerkowski

  2. Biochemisches Forschungslabor, Medizinische Klinik und Poliklinik, Abteilung Nieren- und Hochdruckkrankheiten, Universitätsklinikum Essen, Hufelandstrasse 55, W-4300, Essen 1, Federal Republic of Germany

    Andrea Broede, Klaus Kunde, Steffen Hillemann, Ellen Schäfer, Magdalene Vogelsang, Martin C. Michel & Otto-Erich Brodde

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  1. Hans-Reinhard Zerkowski
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  2. Andrea Broede
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  3. Klaus Kunde
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  4. Steffen Hillemann
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  7. Martin C. Michel
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  8. Otto-Erich Brodde
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Correspondence to O. E. Brodde at the above address

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Zerkowski, HR., Broede, A., Kunde, K. et al. Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium. Naunyn-Schmiedeberg's Arch Pharmacol 347, 347–352 (1993). https://doi.org/10.1007/BF00165383

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  • DOI: https://doi.org/10.1007/BF00165383

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