Angiotensin II is well established to increase blood pressure via direct vasoconstriction of blood vessels. However, the longer-term effects are thought to involve increased sympathetic nerve activity . In this study we question whether angiotensin II based hypertension may be mediated by a selective increase in sympathetic nerve activity to the kidney. The University of Auckland Animal Ethical Committee approved all experimental procedures. New Zealand white rabbits (3-3.6 kg) were initially anaesthetised with 5% halothane in oxygen with sufficient depth of anaesthesia maintained with 3% halothane during the surgical implantation of telemetry devices and osmotic mini pumps. After recovery from the implantation surgery, the animals were returned to their home cages where they remained for the duration of the experimental protocol. During this period the animals drank 0.9% sodium chloride (NaCl) and arterial pressure (model PA-D70, Data Sciences) and renal sympathetic nerve activity (Telemetry Research Ltd) were recorded continuously using telemetry devices before and during a 23-day infusion of angiotensin II (20 ng/kg/min) via the implanted osmotic mini pump (model 2ML4, Alzet). This dose is slow-pressor and resulted in a significant increase in arterial pressure from 92± to 115±2 mmHg (mean±S.E.M., p<0.05) that took 8-12 days to develop. A second group of rabbits, also drinking 0.9% NaCl were renal denervated and subjected to the same angiotensin II infusion but arterial pressure did not increase over the 3 week period of infusion (83±3 mmHg control c.f. 87±8 mmHg after 14 days angiotensin II). At the completion of the angiotensin II infusion, the animals were killed humanely with sodium pentobarbitone (160 mg/kg), followed by perfusion with heparinised saline and finally with 4% paraformaldehyde. The brains from both groups were removed and underwent Fos immunocytochemistry to investigate activation of the central nervous system including areas of the hypothalamus (paraventricular nucleus and supraoptic nucleus) and medulla (ventral lateral medulla, nucleus tractus solitarius and area postrema). All areas examined showed evidence of activation (presence of Fos positive neurones) in intact and denervated rabbits exposed to salt and angiotensin II (Lohmeier et al. 2002). These data suggest that this slow-pressor dose of angiotensin II is sympatho-excitatory and that, in particular, the renal nerves are important for the development of the induced hypertension.