Central and peripheral alpha-adrenoceptor number and responsiveness after sinoaortic denervation in the rabbit.

Abstract

The effects of bilateral sinoaortic denervation were examined in rabbits in vivo and in vitro. In the in vivo studies the effects of intravenous administration of the alpha-adrenoceptor agonists phenylephrine and guanabenz and the antagonists prazosin and phentolamine on mean arterial pressure, heart rate, and plasma catecholamine levels were investigated in intact sham-operated rabbits and after bilateral baroreceptor deafferentation. In in vitro studies the maximum number of prazosin and clonidine binding sites and their dissociation constants were investigated using radioligand binding techniques. Mean arterial pressure was labile and significantly elevated in the sinoaortic denervated rabbits. Heart rate and basal plasma noradrenaline were also raised, but plasma adrenaline and tissue noradrenaline levels were similar in intact and debuffered animals. alpha-Adrenoceptor antagonists were more effective at lowering mean arterial pressure in the sinoaortic-denervated animals. This was at least in part the result of a lack of compensatory changes in sympathetic activity and heart rate in these animals. Pressor responses to the alpha 1-adrenoceptor agonist and more markedly to the alpha 2-adrenoceptor selective agonist were increased after sinoaortic denervation. These changes could not be related to alteration in alpha 1- or alpha 2-receptor binding in either heart, spleen, or brain tissue as there was no change in number of binding sites or affinity.