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 alpha1-adrenoceptors. This study examines the possibility that the vascular adrenergic hyporesponsiveness is due to down-regulation of vascular alpha1-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 alpha1-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 alpha1-adrenoceptors.
Conclusions: Since the affinity and number of vascular alpha1-adrenoceptors were unchanged in the face of elevated plasma concentrations of catecholamines in the BDL rats, we have concluded that down-regulation of vascular alpha1-adrenoceptors does not account for the vascular adrenergic hyporesponsiveness in experimental cholestasis.