The low-pressure baroreceptors are sensitive to circulatory volume and initiate a reflex renal sympatho-excitation or inhibition. This study investigated the contribution of NO to low pressure baroreceptor regulation of RSNA and whether there was a role for AT2 receptors. Groups of Wistar rats (275-350g) were anaesthetised with 1ml chloralose/urethane mixture (16.5/250mg/ml) IP. Cannulae were inserted into the right femoral artery, for mean arterial pressure (MAP) and heart rate (HR) measurement, and vein for saline (NaCl, 9g/L) infusion and supplementary anaesthetic. A cannula was placed in the right intracerebroventricle (ICV) for infusion of drugs. The left kidney was exposed, a renal sympathetic nerve dissected and sealed onto recording electrodes. Saline was infused ICV at 30µl/h for 10min followed by a maintenance infusion of 7.5µl/h for 30min after which the first volume expansion was performed by infusing saline at 0.25% bwt/min IV for 30min. Thereafter, the ICV infusion was switched to either PD123319 (PD, 50µg/kg/min), an AT2 receptor antagonist (n=6) or L-NAME (LNM, 150µg/kg/min), a NO synthase inhibitor (n=8) after which a second volume expansion was performed. Another group of rats received ICV PD or LNM initially followed by PD+LNM as combination (n=6 and 7, respectively). Baseline MAP, HR and RSNA were recorded for 5 min before starting the first and second volume expansion. Data, mean±SEM were analysed using the Student’s t-test with significance at P<0.05. Animals were killed with an anaesthetic overdose. MAP, HR and RSNA following either PD (75±6mmHg, 319±20bpm, 0.69±0.17µV.s) or LNM (82±7mmHg, 304±14bpm, 0.95±0.33µV.s) were not different from those following saline infusion (67±4mmHg, 307±15bpm, 0.82±0.17µV.s; 77±6mmHg, 312±16bpm, 1.00±0.1µV.s respectively). MAP was increased after ICV PD+LNM compared to either PD or LNM (PD+LNM vs. PD, 77±5 vs. 64±7mmHg and PD+LNM vs. LNM 89±5 vs. 80±4mmHg; both P<0.05). Volume expansion decreased RSNA in all groups by some 64±10% (P<0.05) at the end of the 30min. Infusion of PD ICV had no effect on the magnitude of the renal sympatho-inhibition. Following ICV LNM, the reduction in RSNA was less compared to that obtained during saline infusion (46±11 vs. 64±10%, P<0.05, respectively). Similarly, in the PD+LNM group where PD preceded LNM, the fall in RSNA was smaller than when PD was infused alone (37±8 vs. 63±7%, P<0.05, respectively) but not if PD was given after the LNM. These findings suggest that NO is important in allowing the normal renal sympatho-inhibition to occur in response to a volume load but that AT2 receptors do not contribute to this reflex mechanism.