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

Wiley - Tập 19 Số 3 - Trang 193-198 - 1999
Kamal Dabagh1, Омар Саид1, Didier Lebrec2,3, Arieh Bomzon1,4
1Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
2Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM, Hôpital Beaujon, Clichy, France
3Laboratoire dcar
4Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

Tóm tắt

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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