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Down-regulated β-adrenoceptors in severely failing human ventricles: Uniform regional distribution, but no increased internalization

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Summary

In chronic heart failure cardiac β-adrenoceptors are decreased. In this study we investigated whether a) in severely failing human ventricles β-adrenoceptors are uniformly decreased or regional variations exist, and b) the β-adrenoceptor decrease is caused by increased internalization or is a real loss in β-adrenoceptors. For this purpose we assessed β-adrenoceptor number and subtype distribution in a particulate fraction (mainly sarcolemmal plasma membranes) and a light vesicle fraction of right and left ventricular segments (obtained by cutting transversal, rings of 2 cm from the midventricular regions) of explanted hearts from 2 patients with end-stage congestive dilated cardiomyopathy (DCM) and one patient with end-stage ischemic cardiomyopathy (ICM). In all three hearts ventricular β-adrenoceptor number was very low (7.5–10 and 21–26 fmol/mg protein in DCM, 15–22 fmol/mg protein in ICM compared to 68–74 fmol/mg protein in non-failing ventricles). β-Adrenoceptors were uniformly decreased over the whole ventricular region and no considerable regional variations existed. The same held true for β1- and β2-adrenoceptors. In ICM decrease in β-adrenoceptors was due to a concomitant reduction in β1- and β2-adrenoceptors, in DCM it was mainly caused by β1-adrenoceptor down-regulation. In all ventricular segments investigated light vesicle β-adrenoceptors amounted to about 5–7% of total ventricular β-adrenoceptors and this was not significantly different from non-failing left ventricles. We conclude that a) in severely failing human ventricles β-adrenoceptors are evenly down-regulated and no regional variations exist and b) the decrease in β-adrenoceptors is not due to enhanced internalization but is a real loss of β-adrenoceptors.

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Abbreviations

DCM:

dillted cardiomyopathy

ICM:

ischemic cardiomyopathy

ICI 118,551:

erythro-(±)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol hydrochloride

CGP 12177:

(±)-4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzimidazole-2-on hydrochloride

ICYP:

(−) [125I]-Iodocyanopindolol

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Authors and Affiliations

  1. Kerckhoff-Klinik, Bad Nauheim, Germany

    H. F. Pitschner, M. Mitze & M. Schlepper

  2. Department of Internal Medicine, University of Essen, Germany

    A. Droege & O. -E. Brodde

  3. Biochemisches Forschungslabor, Med. Klinik & Poliklinik, Abtlg. Nieren- & Hochdruckkrankheiten, Universitätsklinikum, Hufelandstr. 55, D-4300, Essen 1, Germany

    O. -E. Brodde

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  1. H. F. Pitschner
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  3. M. Mitze
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  4. M. Schlepper
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  5. O. -E. Brodde
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Pitschner, H.F., Droege, A., Mitze, M. et al. Down-regulated β-adrenoceptors in severely failing human ventricles: Uniform regional distribution, but no increased internalization. Basic Res Cardiol 88, 179–191 (1993). https://doi.org/10.1007/BF00798266

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  • DOI: https://doi.org/10.1007/BF00798266

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