Subpressor angiotensin II infusions do not stimulate sympathetic activity in humans

Angiotensin II (ANG II) exerts significant direct and indirect pressor and chronotropic effect in experimental animals. The indirect effects have been shown to be due to interactions with the sympathetic nervous system at several levels. To test the hypothesis that ANG II in subpressor doses enhances the activity of the sympathetic nervous system in humans either at rest or in response to a stimulus from baroreceptor unloading, we measured mean arterial pressure (MAP), heart rate (HR), plasma norepinephrine (NE), and plasma NE kinetics during infusions of ANG II at 2 ng · kg^-1 · min^-1 [or 5% dextrose in water (D5/W) control] in six healthy volunteers in the supine position and during 60° head-up tilt. No changes in any measured variable occurred during either infusion in the supine position. During upright tilt with D5/W, HR increased (58 ± 8.4 to 68 ± 7.7 beats/min, P < 0.005), MAP rose slightly (90 ± 3.9 to 94 ± 4.0 mmHg, P < 0.005), and plasma NE increased (213 ± 3.8 to 366 ± 83 pg/ml, P < 0.005). The responses of the variables to tilt during ANG II were not different from those with D5/W. NE spillover rose from 351 ± 53 to 520 ± 59 ng/ml during tilt (P < 0.005) with D5/W, and NE clearance declined nonsignificantly from 1.6 ± 0.11 to 1.4 ± 0.15. With ANG II, spillover increased from 472 ± 81 to 528 ± 119 ng/ml, but the change was not significant, and the decrease in NE clearance was more pronounced (1.8 ± 0.10 to 1.4 ± 0.19, P < 0.05). Nonpressor infusions of ANG II do not therefore activate the sympathetic nervous system at rest, nor do they enhance the sympathetic response to upright tilt. The mechanisms of the increase in plasma NE during tilt in the presence of ANG II may involve a relatively greater contribution from decreased NE clearance than increased NE spillover.