Down-regulation of vascular α1-adrenoceptors does not account for the loss of vascular responsiveness to catecholamines in experimental cholestasis

Authors

  • Kamal Dabagh,

    1. Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
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  • Omar Said,

    1. Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
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  • Didier Lebrec,

    1. Laboratoire dcar;Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM, Hôpital Beaujon, Clichy, France
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  • Arieh Bomzon

    Corresponding author
    1. Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
    2. Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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Dr. Arieh Bomzon, Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, P.O. Box 9649, Haifa, Israel 31096

Abstract

Abstract: Aims/Background: Vascular hyporesponsiveness to sympathomimetic stimulation occurs in jaundice. Recently, we reported that this vascular adrenergic hyporesponsiveness was associated with the loss of reactivity of vascular α1-adrenoceptors. This study examines the possibility that the vascular adrenergic hyporesponsiveness is due to down-regulation of vascular α1-adrenoceptors. Methods: This question was addressed by measuring the changes in the plasma norepinephrine (NE) and epinephrine (E) concentrations, determined by high performance liquid chromatography, and the affinity and number of α1-adrenoceptors determined by a competitive antagonist radioligand binding assay in vascular smooth muscle membranes prepared from 3-day bile duct ligated (BDL) rats. The results were compared to data obtained from 3-day bile duct manipulated (sham-operated; SO) and control (C) rats. Results: Compared to C and SO rats, the plasma concentrations of NE and E in the BDL rats were significantly elevated reflecting increased sympathetic nervous system activity. BDL did not change either the affinity or the number of vascular α1-adrenoceptors. Conclusions: Since the affinity and number of vascular α1-adrenoceptors were unchanged in the face of elevated plasma concentrations of catecholamines in the BDL rats, we have concluded that down-regulation of vascular α1-adrenoceptors does not account for the vascular adrenergic hyporesponsiveness in experimental cholestasis.

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