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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

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

Discipline of Physiology, School of Medical Sciences and Bosch Institute, University of Sydney, New South Wales, Australia

Submitted 18 April 2007 ; accepted in final form 11 September 2007

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.

arterial pressure; heart rate; renal sympathetic nerve activity; area postrema

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