Expression of beta-adrenoceptors on circulating mononuclear cells in hypertensives and normotensives before and after reduction of central sympathetic outflow by clonidine.
We have studied beta-adrenoceptor number and affinity on peripheral blood mononuclear cells (PBMCs) in normotensives (NT) and hypertensives (HT), before and after intravenous administration of clonidine, an alpha 2-adrenoceptor agonist which lowers blood pressure predominantly by reducing central nervous system sympathetic outflow. After clonidine, there was a decrease in blood pressure and plasma noradrenaline (NA) and adrenaline (Ad) levels, with an increase in growth hormone (GH) levels, in both NT and HT. There was no difference in basal beta-adrenoceptor densities on PBMCs between NT and HT. After clonidine at 30 and 60 min, there was an increase in beta-adrenoceptor density associated with a low affinity in NT. In HT, no changes were observed. The increased beta-adrenoceptor densities on PBMCs in NT after clonidine, returned to baseline values after 2 h. Short term up-regulation of beta-adrenoceptors on PBMCs in NT after clonidine is accompanied by a fall in blood pressure (BP) and plasma levels of catecholamines. The changes may represent a compensatory mechanism reflecting a rapid externalization-activation of adrenoceptors residing on the internal surface of the membranes with a change of the coupling ability between the receptor and the catalytic component. In HT, although the haemodynamic and neurohormonal response to clonidine was similar to NT, short term upregulation of receptors did not occur. The lack of such response may mirror a form of regulatory dysfunction of beta-adrenoceptors in HT.
Zoukos
Y
Y
Department of Neurochemistry, National Hospital for Neurology and Neurosurgery, London, UK.
Thomaides
T
T
Chaudhuri
K R
KR
Pavitt
D V
DV
Cuzner
M L
ML
Mathias
C J
CJ
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D011943:Receptors, Adrenergic, beta; D013006:Growth Hormone; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine