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Adrenoceptors in myocardial regulation: concomitant contribution from both alpha- and beta-adrenoceptor stimulation to the inotropic response

  • Cellular And Subcellular Mechanisms, Energy Turnover
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Summary

The studies presented deal with theα 1-adrenoceptor mediated inotropic effects of noradrenaline obtained by exclusive (“pure”)α 1-adrenoceptor stimulation or by concomitant stimulation ofα 1- andβ-adrenoceptors in myocardium. The pureβ-adrenergic effects of noradrenaline were also quantified. Interactions between the two receptors system were studied. The pureα 1- andβ-adrenergic effects of noradrenaline, respectively, were achieved separately in the presence of high concentrations of appropriate receptor blockers. The experiments were performed on isolated ventricular myocardium from rat, rabbit, and man.

The pureα 1-adrenergic inotropic effects were about 35–50% of control (basal) and half the pureβ-adrenergic effects both in rat and rabbit myocardium. Ventricular myocardium from man exhibited anα 1-adrenergic inotropic effect of the same magnitude (50% of control [basal]) as did rabbit papillary muscle.

Determination of theα 1-adrenergic inotropic component during concomitantβ-adrenoceptor stimulation was associated with difficulties. Several experimental approaches on rat and rabbit myocardium are presented and discussed. Some types of experimental approaches obviously underestimate theα 1-adrenergic component. The methods regarded as reliable revealed anα 1-adrenergic inotropic effect of about 20–30% during combined adrenoceptor stimulation by noradrenaline. Concomitantβ-stimulation reduced theα 1-adrenergic effect by about 50%, whileα 1-stimulation attenuated theβ-effect to a lesser degree (about 20–25%). A model is presented on a mutual attenuation of the functional expression of the two receptor systems. Thus theα 1-adrenergic inotropic component increases when theβ-adrenergic stimulation is antagonized and theβ-effect largely compensates for the loss of theα 1-effect during myocardialα 1-adrenoceptor blockade.

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Authors and Affiliations

  1. Department of Pharmacology, University of Oslo, Norway

    J. B. Osnes, H. Aass & T. Skomedal

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  1. J. B. Osnes
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  2. H. Aass
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  3. T. Skomedal
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Supported by the Norwegian Research Council for Science and the Humanities and the Norwegian Council on Cardiovascular Diseases.

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Osnes, J.B., Aass, H. & Skomedal, T. Adrenoceptors in myocardial regulation: concomitant contribution from both alpha- and beta-adrenoceptor stimulation to the inotropic response. Basic Res Cardiol 84, 9–17 (1989). https://doi.org/10.1007/BF02650342

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