Involvement of AT₂ receptors at NRVL in tonic baroreflex suppression by endogenous angiotensins

We evaluated the role of endogenous angiotensin II and III (ANG II and ANG III) at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved in this process. Adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium were used. Exogenous application of ANG II or ANG III (10, 20, or 40 pmol) by bilateral microinjection into the NRVL significantly suppressed the BRR response to transient hypertension induced by phenylephrine (5 μg/kg iv). The suppressive effect of ANG II (20 pmol) was reversed by an equimolar dose (1.6 nmol) of its peptide antagonist, [Sar¹,Ile⁸]ANG II, and the nonpeptide antagonists for AT₁ and AT₂ receptors, losartan and PD-123319, respectively. On the other hand, the inhibitory action of ANG III (20 pmol) was blunted by its peptide antagonist, [Ile⁷]ANG III or PD-123319, but not by losartan. Blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of [Sar¹,Ile⁸]ANG II, [Ile⁷]ANG III, or PD-123319 elicited an appreciable enhancement of the BRR response, whereas losartan produced minimal effect. These results suggest that, under physiological conditions, both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the BRR response by acting selectively on the AT₂ receptors at the NRVL.