Down-regulation of vascular alpha1-adrenoceptors does not account for the loss of vascular responsiveness to catecholamines in experimental cholestasis.
OBJECTIVE
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.
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
K
K
Dabagh
O
O
Said
D
D
Lebrec
A
A
Bomzon
D000818:Animals; D002395:Catecholamines / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D002395:Catecholamines; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine; D004837:Epinephrine