Down-regulation of vascular alpha(1)-adrenoceptors does not account for the loss of vascular responsiveness to catecholamines in experimental cholestasis

Aims/Background: Vascular hyporesponsiveness to sympathomimetic stimulation occurs in jaundice. Recently, we reported that this vascular adrenergic hy poresponsiveness was associated with the loss of reactivity of vascular alp ha 1-adrenoceptors. This study examines the possibility that the vascular a drenergic hyporesponsiveness is due to down-regulation of vascular alpha 1- adrenoceptors. Methods: This question was addressed by measuring the change s in the plasma norepinephrine (NE) and epinephrine (E) concentrations, det ermined by high performance liquid chromatography, and the affinity and num ber of alpha 1-adrenoceptors determined by a competitive antagonist radioli gand binding assay in vascular smooth muscle membranes prepared from 3-day bile duct ligated (BDL) rats. The results were compared to data obtained fr om 3-day bile duct manipulated (sham-operated; SO) and control (C) rats. Re sults: Compared to C and SO rats, the plasma concentrations of NE and E in the BDL rats were significantly elevated reflecting increased sympathetic n ervous system activity. BDL did not change either the affinity or the numbe r of vascular alpha 1-adrenoceptors. Conclusions: Since the affinity and nu mber of vascular alpha 1-adrenoceptors were unchanged in the face of elevat ed plasma concentrations of catecholamines in the BDL rats, we have conclud ed that down-regulation of vascular alpha 1-adrenoceptors does not account for the vascular adrenergic hyporesponsiveness in experimental cholestasis.