Differential rates of down regulation and recovery of rat myocardial beta-adrenoceptor subtypes in vivo.

We have investigated the differential rate and extent of down regulation and recovery of rat myocardial beta adrenoceptor subtypes during and after short term (up to 72 h) subcutaneous isoprenaline infusions (40 micrograms/kg per h) in vivo using osmotic minipumps. Maximum density (Bmax) of the receptors in ventricular membranes was assessed by radioligand binding, saturation analysis using 125I-pindolol. Groups of animals were sacrificed following various agonist infusion times and then during recovery after removal of minipumps following initial infusion of isoprenaline for 72 h. During agonist infusion, beta 2 adrenoceptors down regulated significantly more rapidly and to a greater extent than the beta 1 subtype (maximum change from control 66% beta 2, 34% beta 1 P less than 0.05). In the recovery phase of the experiments following initial maximum down regulation, beta 2 adrenoceptor density also returned to control values more rapidly (by 24 h) than the beta 1 subtype (greater than 72 h). These results are qualitatively different to those reported in other tissues from this species using selective and non selective catecholamine agonists and in human myocardium in end stage heart failure following chronic sympathetic nervous stimulation. This may be due to differences in tissue cellular composition, the nature/selectivity of the agonist or the length of time of agonist exposure.