Baroreceptor reflex modulation by circulating angiotensin II is mediated by AT1 receptors in the nucleus tractus solitarius.

Circulating ANG II modulates the baroreceptor reflex control of heart rate (HR), at least partly via activation of ANG II type 1 (AT1) receptors on neurons in the area postrema. In this study, we tested the hypothesis that the effects of circulating ANG II on the baroreflex also depend on AT1 receptors within the nucleus tractus solitarius (NTS). In confirmation of previous studies in other species, increases in arterial pressure induced by intravenous infusion of ANG II had little effect on HR in urethane-anesthetized rats, in contrast to the marked bradycardia evoked by equipressor infusion of phenylephrine. In the presence of a continuous background infusion of ANG II, the baroreflex control of HR was shifted to higher levels of HR but had little effect on the baroreflex control of renal sympathetic activity. The modulatory effects of circulating ANG II on the cardiac baroreflex were significantly reduced by microinjection of candesartan, an AT1 receptor antagonist, into the area postrema and virtually abolished by microinjections of candesartan into the medial NTS. After acute ablation of the area postrema, a background infusion of ANG II still caused an upward shift of the cardiac baroreflex curve, which was reversed by subsequent microinjection of candesartan into the medial NTS. The results indicate that AT1 receptors in the medial NTS play a critical role in modulation of the cardiac baroreflex by circulating ANG II via mechanisms that are at least partly independent of AT1 receptors in the area postrema.

Angiotensin II evokes hypotension and renal sympathoinhibition from a highly restricted region in the nucleus tractus solitarii.

Microinjections of low doses (in the femtomolar or low picomolar range) of angiotensin II (Ang II) into the nucleus tractus solitarii (NTS) evoke depressor responses. In this study we have mapped in the rat the precise location of the subregion within the NTS at which Ang II evokes significant sympathoinhibitory and depressor responses. Microinjections of 1 pmol of Ang II evoked large decreases (>or=20% of baseline) in renal sympathetic nerve activity (RSNA), from a highly restricted region in the medial NTS, at or very close to the level 0.2 mm caudal to the obex. Microinjections of the same dose of Ang II into the commissural or lateral NTS at the same rostrocaudal level, or into the medial and lateral NTS at the level of the obex evoked significantly smaller sympathoinhibitory responses, while microinjections into more rostral or caudal levels of the NTS evoked significant sympathoinhibitory responses even less frequently. In most cases (71%), the sympathoinhibitory responses were accompanied by depressor responses, the magnitudes of which were also greater within the medial NTS at the level 0.2 mm caudal to obex, as compared to the surrounding subregions. The results demonstrate that the cardiovascular effects of Ang II in the NTS are highly site-specific. Taken together with previous studies, the results also indicate that the neurons in the NTS that mediate the Ang II-evoked sympathoinhibition are a discrete subgroup of the population of sympathoinhibitory neurons within the nucleus.