Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis inthe rat

We evaluated the role of endogenous angiotensins at the rostral nucleus ret icularis ventrolateralis (NRVL) in the modulation of spontaneous barorecept or reflex (BRR) response and the subtype of angiotensin receptors involved using rats anesthetized and maintained with pentobarbital sodium. Bilateral microinjection of angiotensin II (ANG II) or its active metabolite angiote nsin III (ANG III) (5, 10, or 20 pmol) into the NRVL significantly suppress ed the spontaneous ERR response, as represented by the magnitude of transfe r function between systemic arterial pressure and heart rate signals. The i nhibitory effect of ANG III (20 pmol) was discernibly reversed by coadminis tration with its peptide antagonist, [Ile(7)]ANG III (1.6 nmol), or the non peptide AT, receptor antagonist, PD-123319 (1.6 nmol), but not by the nonpe ptide AT, receptor antagonist, losartan (1.6 nmol). On the other hand, the peptide antagonist, [Sar(1), Ile(8)]ANG II (1.6 nmol) or both non-peptide a ntagonists appreciably reversed the suppressive action of ANG II (20 pmol). Whereas losartan produced minimal effect, blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of PD-123319 , [Sar(1), Ile(8)]ANG II or [Ile(7)]ANG III elicited significant enhancemen t of the spontaneous ERR response. We conclude that under physiologic condi tions both endogenous ANG II and ANG III may exert a tonic inhibitory modul ation on the spontaneous ERR response by acting selectively on the AT, subt ype receptors at the NRVL. (C) 2001 Wiley-Liss, Inc.