PARTICIPATION OF AT(1) AND AT(2) RECEPTOR SUBTYPES IN THE TONIC INHIBITORY MODULATION OF BARORECEPTOR REFLEX RESPONSE BY ENDOGENOUS ANGIOTENSINS AT THE NUCLEUS-TRACTUS-SOLITARII IN THE RAT

We evaluated the endogenous action of angiotensin II (AII) and its act ive metabolite, angiotensin III (AIII), at the nucleus tractus solitar ii (NTS) in the modulation of baroreceptor reflex (ERR) response, and the subtype(s) of angiotensin receptors involved in this process. Adul t, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium were used. Bilateral microinjection of AII or AI II (10, 20 or 40 pmol) into the NTS significantly and dose-dependently suppressed the ERR response, which was evoked by transient hypertensi on induced by phenylephrine (5 mu g/kg, i.v.). The suppressive effect of AII (40 pmol) was reversed by co-administration of the non-peptide AT(1) receptor antagonist, losartan (1.6 nmol), but only partially by the non-peptide AT(2) receptor antagonist, PD-123319. On the other han d, both angiotensin receptor antagonists appreciably reversed the depr essive action of AIII (40 pmol). Blocking the endogenous activity of t he angiotensins by microinjection into the bilateral NTS of losartan ( 1.6 nmol) or PD-123319 (1.6 nmol) elicited a significant enhancement o f the BRR response. An interruption of the conversion of AII to AIII w ith 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 inhibi tory modulation on the BRR response by acting on both the AT(1) and AT (2) receptor subtypes, the same action of the endogenous AII engaged o nly the AT(1) receptor subtype at the NTS. Furthermore, at least part of the suppressive action of AII may result from its metabolic convers ion to AIII. (C) 1998 Elsevier Science B.V.