Chronic Infusion of Angiotensin II Resets Baroreflex Control of Heart Rate by an Arterial Pressure–Independent Mechanism

Abstract

Abstract The purpose of this study was to test the hypothesis that chronic infusion of angiotensin II (Ang II) in rabbits resets the cardiac baroreflex to a higher arterial pressure level by a pressure-independent mechanism. This hypothesis was tested by determining whether the resetting would be reversed soon after the Ang II infusion was stopped even if the hypertension was maintained by infusion of another vasoconstrictor. Relationships between arterial pressure and heart rate were determined by infusion of increasing doses of nitroprusside to decrease pressure and increase heart rate, followed by increasing doses of phenylephrine to increase pressure and decrease heart rate. After 9 to 10 days of Ang II infusion (20 ng · kg −1 · min −1 ) arterial pressure was increased from 62±2 to 94±3 mm Hg ( P <.001), and heart rate was unchanged from control values of 126±7 beats per minute. The baroreflex relationship between arterial pressure and heart rate was shifted to a higher pressure level after 3 to 4 and 9 to 10 days of Ang II infusion. On these same days the Ang II infusion was replaced with phenylephrine (5.0±0.4 μg · kg −1 · min −1 ), and 30 minutes later arterial pressure decreased slightly ( P <.05); however, despite the relative hypotension, heart rate was decreased ( P <.005) from 126±5 to 98±7 beats per minute (days 3 to 4) and from 132±4 to 103±7 beats per minute (days 9 to 10). Moreover, the cardiac baroreflex relationships were shifted back to a lower pressure level ( P <.05). Similar results were found when Ang II was replaced with methoxamine (1.7 μg · kg −1 · min −1 ). These data indicate that angiotensin-induced chronic baroreflex resetting is partially reversed soon after Ang II infusion is stopped, despite maintenance of the hypertensive state, and suggest that long-term increases in angiotensin reset the cardiac baroreflex in part by an arterial pressure–independent mechanism.