Tonic reduction in central alpha 2-adrenoceptor activity by endogenous angiotensin III in the rat.

We evaluated the possible interactions between central alpha 2-adrenoceptors and endogenous angiotensin III (AIII) in Sprague-Dawley rats anesthetized with pentobarbital sodium (50 mg/kg, i.p.). The cardiovascular suppressive effects of the alpha 2-adrenoceptor agonist, guanabenz, were used as our experimental index for alpha 2-adrenoceptor activity. Intracerebroventricular (i.c.v.) administration of AIII (100 or 200 pmol) attenuated the hypotensive and negative inotropic and chronotropic actions of guanabenz (100 micrograms/kg, i.v.). Blocking the endogenous activity of the heptapeptide with its specific antagonist, Ile7-AIII (50 or 100 nmol, i.c.v.), on the other hand, potentiated the circulatory inhibitory efficacy of the aminoguanidine compound. These modulatory effects were essentially duplicated by bilateral microinjection of AIII (20 or 40 pmol) or Ile7-AIII (10 or 20 nmol) into the nucleus reticularis gigantocellularis (NRGC), a medullary site that is critically involved in the cardiovascular suppressive actions of guanabenz. I.c.v. injection of bestatin (200 nmol) also reduced the circulatory depressive potency of guanabenz. This effect was respectively enhanced and reduced when the aminopeptidase inhibitor was given simultaneously with AIII (200 pmol) and Ile7-AIII (100 nmol). These results suggest that the endogenous AIII may exert a tonic inhibition on the alpha 2-adrenoceptors in in the NRGC that are involved in cardiovascular regulation.