Central angiotensin II plays a critical role in the regulation of cardiovascular function and autonomic activity, in part, via angiotensin type 1 receptors in the rostral ventrolateral medulla (RVLM). Increasing evidence indicates that angiotensin II can also act on angiotensin type 2 receptors (AT(2)Rs) to exert antagonistic effects. In the current study we determined the effects of overexpression of AT(2)R in the RVLM on sodium and water excretion and on blood pressure in conscious rats. The overexpression of AT(2)R was induced by bilateral microinjection of the AT(2)R adenovirus (Ad5-SYN-AT2R-IRES-EGFP, 2.5 x 10(6) infection units in 0.5 microL; Ad5-SYN-EGFP as the control, 2.5 x 10(6) infection units in 0.5 microL) into the RVLM of rats. Immunofluorescence staining showed that microinjection of AT(2)R adenovirus into the RVLM evoked local overexpression. Significant overexpression of AT(2)R in the RVLM began at 24 hours and was sustained up to 12 days after microinjection. Overexpression of AT(2)R in the RVLM significantly decreased the nocturnal arterial blood pressure and increased the 24-hour urine excretion at days 2, 3, and 4 after gene delivery compared with the control rats. These alterations were abolished by the microinfusion of captopril into the RVLM and were enhanced by angiotensin II infusion. Overexpression of AT(2)R in the RVLM also significantly decreased the urine concentration of noradrenaline and 24-hour noradrenaline excretion (1.1+/-0.5 microg in control rats and 2.4+/-0.5 microg in AT(2)R rats; P<0.05). These results suggest that overexpression of AT(2)R in the RVLM induced a diuresis that may be mediated, in part, by sympathoinhibition.