Effects of?-adrenoceptor antagonist administration on ?2-adrenoceptors density in human lymphocytes

Publisher Website
Google Scholar
Abstract
Abrupt withdrawal of β-adrenoceptor antagonists may lead to “rebound-effects”. To study the mechanism underlying this phenomenon, the effects of the nonselective β-adrenoceptor antagonists propranolol [no intrinsic sympathomimetic activity (ISA)], alprenolol (weak ISA) and mepindolol (strong ISA) on lymphocyte β2-adrenoceptor density — assessed by (±)-[125I]-iodocyanopindolol (ICYP) binding — and plasma renin activity (PRA) were investigated in male healthy volunteers aged 23–35 years. Propranolol treatment (4×40 mg/day) increased the density of β2-adrenoceptors by 25% after 2 days; concomitantly PRA and heart rate were reduced. During treatment β2-adrenoceptor density remained elevated. After withdrawal of propranolol PRA reached pre-drug levels rapidly, while heart rate was significantly enhanced. β2-Adrenoceptor density, however, declined slowly being still significantly increased after 3 days, although propranolol was not detectable in plasma after 24 h. The affinity of ICYP to β2-adrenoceptors was not changed during or after treatment. Mepindolol treatment (2×5 mg/day) caused a 30% decrease of β2-adrenoceptor density and PRA after 2 days; both parameters remained reduced during treatment. After withdrawal, PRA reached rapidly pre-drug levels, whereas β2-adrenoceptor density was still after 4 days significantly diminished. TheK D-values for ICYP, however, were not changed. During and after treatment heart rate was not affected. Alprenolol treatment (4×100 mg/day) led to a rapid fall in PRA, but did not significantly affect β2-adrenoceptor density. It is concluded, that the ISA may play an important role in modulating β2-adrenoceptor density and hence tissue responsiveness to β-adrenoceptor stimulation. Propranolol (no ISA) caused increase in β2-adrenoceptor density still persisting after withdrawal, which might explain the “propranolol rebound-effect”. Since β-adrenoceptor antagonists with ISA did not increase, but rather decrease β2-adrenoceptor density, such “rebound-effects” may not occur after rapid cessation of drug treatment.