Participation of AT1 and AT2 receptor subtypes in the tonic inhibitory modulation of baroreceptor reflex response by endogenous angiotensins at the nucleus tractus solitarii in the rat

Abstract

We evaluated the endogenous action of angiotensin II (AII) and its active metabolite, angiotensin III (AIII), at the nucleus tractus solitarii (NTS) in the modulation of baroreceptor reflex (BRR) response, and the subtype(s) of angiotensin receptors involved in this process. Adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium were used. Bilateral microinjection of AII or AIII (10, 20 or 40 pmol) into the NTS significantly and dose-dependently suppressed the BRR response, which was evoked by transient hypertension induced by phenylephrine (5 micrograms/kg, i.v.). The suppressive effect of AII (40 pmol) was reversed by co-administration of the non-peptide AT1 receptor antagonist, losartan (1.6 nmol), but only partially by the non-peptide AT2 receptor antagonist, PD-123319. On the other hand, both angiotensin receptor antagonists appreciably reversed the depressive action of AIII (40 pmol). Blocking the endogenous activity of the angiotensins by microinjection into the bilateral NTS of losartan (1.6 nmol) or PD-123319 (1.6 nmol) elicited a significant enhancement of the BRR response. An interruption of the conversion of AII to AIII with the aminopeptidase A inhibitor, amastatin (3.3 nmol), attenuated, but did not eliminate, the AII-induced inhibition of the BRR response. We conclude that whereas the endogenous AIII may exert a tonic inhibitory modulation on the BRR response by acting on both the AT1 and AT2 receptor subtypes, the same action of the endogenous AII engaged only the AT1 receptor subtype at the NTS. Furthermore, at least part of the suppressive action of AII may result from its metabolic conversion to AIII.