Role of the area postrema in the modulation of the baroreflex control of heart rate by angiotensin II

During angiotensin II (Ang II)-induced elevation of arterial pressure, there is an attenuation of the baroreflex control of heart rate (HR), but the site of this action of Ang II on the baroreflex is not known. To investigate the role of the area postrema, the effects of Ang II on arterial pressure and HR and on the baroreflex control of HR were compared in intact and area postrema-lesioned conscious rabbits. In intact rabbits, infusion of Ang II (2.5-100 ng/kg/min) produced dose-related increases in mean arterial pressure (MAP); the largest dose increased MAP by 32 +/- 3 mm Hg. HR decreased only at the highest dose of Ang II (21 +/- 6 beats/min). In lesioned rabbits, the increase in MAP was reduced (23 +/- 2 mm Hg, p less than 0.05) while the decrease in HR was enhanced (50 +/- 8 beats/min, p less than 0.01). The pressor and HR responses to infusion of phenylephrine (PE) (2-20 micrograms/kg/min) were not different between the two groups. In intact rabbits, the slope of the relation between HR and MAP during Ang II infusion was less than that during PE infusion; in lesioned rabbits, the slopes were not significantly different. Responses to bolus injections of Ang II and PE in intact and lesioned rabbits were similar to those obtained in the infusion study. In another series of experiments, cardiac baroreflex responses with or without background infusion of Ang II were obtained by increasing blood pressure with graded infusions of PE (2-20 micrograms/kg/min). In intact rabbits, infusion of Ang II at 10 ng/kg/min shifted the baroreflex to a higher pressure level (resetting) without changing its slope (sensitivity). Background infusion of PE caused comparable increases in blood pressure, but the subsequent baroreflex response was identical to the response without background PE. In lesioned rabbits, background infusion of Ang II did not change the slope, nor did it reset the baroreflex. The effects of Ang II on baroreflex responses during nitroprusside infusions (2-20 micrograms/kg/min) in intact and lesioned rabbits were the same as those observed during the PE infusions. These findings indicate that the attenuation of the baroreflex control of HR by Ang II results from resetting of the cardiac baroreflex and suggest that this effect is mediated via the area postrema.