Chronic ANG II infusion and reflex control of norepinephrine and corticosterone in conscious rabbits

The hypothesis that long-term increases in angiotensin II (ANG II) produce pressure-independent resetting of baroreflex control of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis was tested in rabbits by determining the effect of chronic ANG II infusion on reflex relationships between mean arterial pressure (MAP) and plasma concentrations of norepinephrine (NE) and corticosterone (CS). After 2 wk, ANG II increased MAP from 61 ± 1 to 99 ± 2 mmHg (P < 0.05) without altering heart rate or plasma NE concentration, but increased CS from 9.8 ± 1.3 to 29.5 ± 13.7 ng/ml (P < 0.05). Heart rate, NE, and CS baroreflex curves were all reset to a higher pressure level (P < 0.05) after 24 h, 1 wk, and 2 wk of ANG II. Forty minutes after stopping ANG II on the same days, MAP decreased, and curves were shifted back toward control (P < 0.05), indicating that ANG II was required for the resetting. Two findings suggest that the resetting action of ANG II is distinct from the presser effect. First, although stopping ANG II reversed the hypertension as it reversed the resetting, reversal of the hypertension instead by prolonged infusion of nitroprusside along with ANG II did not have the same effect. Second, NE and heart rate baroreflex curves returned toward preinfusion positions after stopping ANG II (P < 0.05), even when the hypertension was nearly maintained by phenylephrine infusion. In conclusion, chronic increases in ANG II may have a global baroreflex resetting effect by a mechanism that is in part independent of the hypertension.