Effects of angiotensin type 2 receptor overexpression in the rostral ventrolateral medulla on blood pressure and urine excretion in normal rats

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 (AT2Rs) to exert antagonistic effects. In the current study we determined the effects of overexpression of AT2R in the RVLM on sodium and water excretion and on blood pressure in conscious rats. The overexpression of AT2R was induced by bilateral microinjection of the AT2R adenovirus (Ad5-SYN-AT2R-IRES-EGFP, 2.5 x 10 infection units in 0.5 μL; Ad5-SYN-EGFP as the control, 2.5 x 10 infection units in 0.5 μL) into the RVLM of rats. Immunofluorescence staining showed that microinjection of AT2R adenovirus into the RVLM evoked local overexpression. Significant overexpression of AT2R in the RVLM began at 24 hours and was sustained up to 12 days after microinjection. Overexpression of AT2R 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 AT2R in the RVLM also significantly decreased the urine concentration of noradrenaline and 24-hour noradrenaline excretion (1.1±0.5 μg in control rats and 2.4±0.5 μg in AT2R rats; P<0.05). These results suggest that overexpression of AT2R in the RVLM induced a diuresis that may be mediated, in part, by sympathoinhibition.