Reduction in postsynaptic α₂-adrenoceptor activity by endogenous angiotensin III in the nucleus reticularis gigantocellularis of the rat

We investigated in adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium the synaptic location of the interaction between endogenous angiotensin III (AIII) and the α₂-adrenoceptors in the medulla oblongata that are involved in cardiovascular regulation. The circulatory suppressant efficacy of a centrally acting α₂-adrenoceptor agonist, guanabenz, was used as the experimental index. Direct bilateral microinjection of AIII (40 pmol) into the nucleus reticularis gigantocellularis (NRGC), a medullary site believed to be intimately related to the cardiovascular inhibitory actions of guanabenz, attenuated, whereas the selective AIII receptor antagonist, Ile⁷-AIII (20 nmol), potentiated, the circulatory suppressant effects of guanabenz (100 μg/kg, i.v.). These two respective actions were essentially unaffected by immunocytochemically verified depletion of noradrenergic nerve terminals in the NRGC, elicited by a selective noradrenergic neurotoxin, DSP4. These data suggest that endogenous AIII may exert a tonic inhibitory action on the α₂-adrenoceptors located postsynaptically on neurons in the NRGC that are involved in central cardiovascular regulation.