SINOAORTIC DENERVATION CAUSES RIGHT ATRIAL BETA-ADRENOCEPTOR DOWN-REGULATION

Rat isolated right atria obtained 1 wk after sinoaortic denervation we re less sensitive to the chronotropic actions of beta-agonists than we re tissues obtained from animals that underwent sham surgery or no sur gery at all. The potencies, but not the maximal responses for two high efficacy agonists, norepinephrine and isoproterenol, were reduced abo ut 3- to 4-fold. Sinoaortic denervation (SAD) caused about a 3-fold de crease in potency and about a 60% decrease in maximal response for a l ow efficacy agonist, prenalterol. The changes in the actions of these agonists occurred in the absence of any changes in the subtype of beta receptor mediating the chronotropic response. The results of analyses of the data for prenalterol showed that SAD caused a decrease in the operational efficacy of this agonist without any changes in its K-D va lue for beta-1 adrenoceptors. SAD had no effect on the responses of th e tissue to blockade of uptake 1 and uptake 2, suggesting no compensat ory changes in the removal processes caused the decreased potency. The results of radioligand binding assays showed that SAD caused a decrea se in the maximal binding of I-125-cyanopindolol without altering its K-D. Also, the results of competition binding assays confirmed the lac k of effect of SAD on the K-D for prenalterol. The SAD-induced changes in the actions of agonists acting at right atrial beta-1 receptors we re caused by a down-regulation of beta-1 adrenoceptors, which probably occurred in response to SAD-induced increases in sympathetic tone.