Effects of chronic pindolol treatment on human myocardial beta 1- and beta 2-adrenoceptor function.

To evaluate the effects of chronic pindolol treatment on human myocardial beta-adrenoceptor, membrane preparations from right atrial auricles from patients on chronic pindolol treatment and from patients not treated with beta-blocker were compared with respect to specific binding of [125I]-iodocyanopindolol [( 125I]-ICYP) and adenylate cyclase (AC) activity. Pindolol treatment was associated with a 25% increase in total beta-adrenoceptor density (72.3 vs. 58.3 fmol/mg protein). This increase was due a 40% increase of the beta 1-adrenoceptor subtype (62.2 vs. 44.3 fmol/mg protein), while beta 2-adrenoceptor density was decreased by about 25% (10.0 vs. 14.0 fmol/mg). Isoprenaline 5 mumol/l (9.7 vs. 14.2 pmol/min/mg) and terbutaline 50 mumol/l (4.9 vs. 8.3 pmol/min/mg protein) stimulated adenylate cyclase activity was reduced, whereas fluoride (10 mmol/l) stimulated cAMP production to the same extent in both groups (9.4 vs 9.4 pmol/min/mg protein). Thus, chronic treatment with pindolol was associated with upregulation of the beta 1-adrenoceptors and a down-regulation of the beta 2-adrenoceptors. The total level of beta-adrenoceptors was slightly increased. In spite of this, adenylate cyclase activity and response was reduced.