Pressure-independent baroreflex resetting produced by chronic infusion of angiotensin II in rabbits

The purpose of this study was to test the hypothesis that chronic infusion of angiotensin II (ANG II) in rabbits shifts or resets baroreflex control of heart rate to a higher pressure level via a mechanism that is independent of the hypertension that is produced. The baroreflex relationship between arterial pressure and heart rate was assessed by first infusing progressively increasing doses of nitroprusside (3, 6, 12, 24, and 48 μg · kg^-1 · min^-1) to lower pressure and then increasing doses of phenylephrine (0.5, 1, 2, 4, and 8 μg · kg^-1 · min^-1) to raise pressure. Two weeks of intravenous ANG II infusion (20 ng · kg^-1 · min^-1) increased plasma ANG II levels from 9 ± 1 to 146 ± 24 pg/ml (P < 0.05), increased arterial pressure from 62 ± 2 to 95 ± 2 mmHg (P < 0.05), and transiently increased heart rate. The baroreflex was shifted to a higher pressure level after 30 min and 1, 3, 7, 9, and 14 days of ANG II infusion. Thirty minutes after the ANG II infusion on days 1, 7, and 14 was stopped, arterial pressure decreased, and the baroreflex shifted back to control, indicating that ANG II was required for the resetting that was produced. However, when the ANG II infusion was continued and arterial pressure was instead reduced for 30 min by infusing nitroprusside on days 3 and 9, the baroreflex relationship between arterial pressure and heart rate remained positioned at a higher pressure level. These data indicate that the chronic baroreflex resetting action of ANG II can be dissociated from effects of ANG II on arterial pressure and suggest that long-term increases in ANG II reset the baroreflex in part by a mechanism that is independent of the rise in arterial pressure.