Vol. 280, Issue 2, 677-685, 1997

Sino-Aortic Denervation Causes Right Atrial Beta Adrenoceptor Down-Regulation¹

Angelina Zanesco , Regina C. Spadari-Bratfisch and Louis A. Barker

Department of Physical Education, State University Paulista, Rio Claro (A.Z.) and Department of Physiology and Biophysics (A.Z., R.C. S-B.) and University of Campinas, Sao Paulo, Brazil and Department of Pharmacology (L.A.B.), LSUMC New Orleans, New Orleans, Louisianna

Rat isolated right atria obtained 1 wk after sinoaortic denervation were less sensitive to the chronotropic actions of -agonists than were tissues obtained from animals that underwent sham surgery or no surgery at all. The potencies, but not the maximal responses for two high efficacy agonists, norepinephrine and isoproterenol, were reduced about 3- to 4-fold. Sino-aortic denervation (SAD) caused about a 3-fold decrease in potency and about a 60% decrease in maximal response for a low 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 value for beta-1 adrenoceptors. SAD had no effect on the responses of the tissue to blockade of uptake 1 and uptake 2, suggesting no compensatory changes in the removal processes caused the decreased potency. The results of radioligand binding assays showed that SAD caused a decrease in the maximal binding of ¹²⁵I-cyanopindolol without altering its K_D. Also, the results of competition binding assays confirmed the lack 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 were caused by a down-regulation of beta-1 adrenoceptors, which probably occurred in response to SAD-induced increases in sympathetic tone.