Alpha-Adrenoceptor regulation in vivo and in vitro in the rabbit.

Abstract

The relationship between alpha-adrenoceptor number and response has been studied in rabbits under a range of physiological and pathological conditions. The effects of irreversible alpha-adrenoceptor blockade, maturation, ageing, oestrogen treatment, adrenaline infusion, perinephritis hypertension and sinoaortic denervation on alpha-adrenoceptor number and response were examined. alpha-Adrenoceptor number was measured by radioligand binding. [3H]Prazosin and [3H]clonidine were used as ligands to measure alpha 1- and alpha 2-adrenoceptor number in spleen and [3H]yohimbine to measure alpha 2-adrenoceptor number on platelets. Responses in vivo were studied by examining the pressor responses to a range of alpha-adrenoceptor agonists. The functional response of platelets was examined in vitro by using the aggregatory response to adrenaline. Reductions in alpha 2-adrenoceptor ligand binding were consistently accompanied by equivalent reductions in alpha 2-adrenoceptor-mediated responses. In contrast large reductions in [3H]prazosin binding were observed with little or no change in alpha 1-adrenoceptor-mediated responses. These results would be consistent with a large receptor reserve for alpha 1-adrenoceptors but few if any spare alpha 2-adrenoceptors in the vasculature or on platelets. Increased responses to both alpha 1- and alpha 2-adrenoceptor agonists were observed in animals with sinoaortic denervation and to alpha 1-adrenoceptor agonists in rabbits with perinephritis hypertension. These increases in response were not accompanied by increases in radioligand binding and may be related to alterations in the coupling of receptor activation to end-organ response.