Angiotensin II-based hypertension and the sympathetic nervous system: The role of dose and increased dietary salt in rabbits

There is accumulating evidence that angiotensin II may exert its hypertensive effect through increasing sympathetic drive. However, this action may be dependent on the dose of angiotensin II as well as salt intake. We determined the effect of different doses of angiotensin II and different levels of salt intake on neurogenic pressor activity. We also examined the effect of renal denervation. New Zealand White rabbits were instrumented to continuously measure arterial pressure. The depressor response to the ganglionic blocker pentolinium tartrate (5 mg kg^-1) was used to assess pressor sympathetic drive on days 0, 7 and 21 of a 20 or 50 ng kg^-1 min ^-1 continuous i.v. angiotensin II infusion. A 50 ng kg^-1 min^-1 infusion caused an immediate increase in pressure (23 ± 5 mmHg), whereas a 20 ng kg^-1 min^-1 infusion caused a slow increase in pressure, peaking by day 12 (17 ± 4 mmHg). The ganglionic blockade profiles indicated sympathoinhibition in the 50 ng kg^-1 min^-1 group by day 7 and sympathoinhibition in the 20 ng kg ^-1 min^-1 group at day 21, corresponding to the development of hypertension. Animals receiving increased dietary salt (0.9% NaCl in drinking water), however, showed a similar slow increase in pressure with 20 ng kg^-1 min^-1 angiotensin II (16 ± 5 mmHg) but no sympathoinhibition at day 21. Bilateral renal denervation delayed the onset but not the extent of hypertension in this group. We conclude that different doses of angiotensin II produce distinct profiles of hypertension and associated changes in pressor sympathetic drive and that increased dietary salt intake disrupts the normal sympathoinhibitory response to angiotensin II-based hypertension.