SELECTIVE DESENSITIZATION OF CARDIAC BETA-ADRENOCEPTORS BY PROLONGED INVIVO INFUSION OF CATECHOLAMINES IN RATS

Abstract

The effects of prolonged in vivo infusion of isoproterenol (400 .mu.g/kg per h) or norepinephrine (200 .mu.g/kg per h) from a minipump on the physiological reactivity and binding properties of cardiac .beta. and .alpha.-1 adrenoceptors were tested in rats. Infusion of either catecholamine significantly reduced the in vitro inotropic and chronotropic potency of isoproterenol in isolated left and right atria, respectively; desensitization was near maximal as early as after 2 h of infusion. No significant change in the density of [3H]dihydroalprenolol-labeled .beta. receptors was evident at this time point in either atrial or ventricular tissue, although isoproterenol decreased binding site density after 7 days of infusion. There was no change in the binding affinity or physiological blocking potency of dihydroalprenolol after isoproterenol infusion. The inotropic potency of phenylephrine in the presence of dihydroalprenolol was unaffected by infusion of either isoproterenol or norepinephrine and methoxamine failed to increase right atrial rate either in control or in isoproterenol-infused rats. There was also no change in the density and affinity of [3H]prazosin binding sites after isoproterenol infusion. These results indicate selective desensitization of cardiac .beta. receptors without changes in .alpha.-1 receptors by prolonged in vivo stimulation with catecholamines. This reaction pattern is different from the well documented effects of hypothyroidism, which include decreased sensitivity of cardiac .beta. and increased sensitivity of cardiac .alpha.-1 receptor-mediated responses in rats. The mechanisms responsible for altered receptor function in the 2 conditions appear to be different.