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(Hypertension. 2008;51:521.)
© 2008 American Heart Association, Inc.

Original Articles Part 2

Effects of Angiotensin Type 2 Receptor Overexpression in the Rostral Ventrolateral Medulla on Blood Pressure and Urine Excretion in Normal Rats

Lie Gao; Weizhong Wang; Wei Wang; Hongwei Li; Colin Sumners; Irving H. Zucker

From the Department of Cellular and Integrative Physiology (L.G., WeizhongW., WeiW., I.H.Z.), University of Nebraska Medical Center, Omaha; and the Department of Physiology and Functional Genomics (H.L., C.S.), University of Florida, Gainesville.

Correspondence to Lie Gao, Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850. E-mail lgao{at}unmc.edu

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, 2.5x10⁶ infection units in 0.5 µL; Ad5-SYN-EGFP as the control, 2.5x10⁶ 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.

Key Words: angiotensin II type 2 receptor • rostral ventrolateral medulla • arterial blood pressure • urine excretion • noradrenaline excretion