Published Online
on December 17, 2007

A more recent version of this article appeared on February 1, 2008

This Article Full Text (PDF) All Versions of this Article: 51/2/521    most recent HYPERTENSIONAHA.107.101717v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gao, L. Articles by Zucker, I. H. Search for Related Content PubMed PubMed Citation Articles by Gao, L. Articles by Zucker, I. H. Related Collections Cardio-renal physiology/pathophysiology ACE/Angiotension receptors

Submitted on September 23, 2007
Revised on October 13, 2007

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; and 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.

^* To whom correspondence should be addressed. E-mail: lgao{at}unmc.edu.

Abstract—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

This article has been cited by other articles:

				R. D. Rudic and D. J. Fulton Pressed for time: the circadian clock and hypertension J Appl Physiol, October 1, 2009; 107(4): 1328 - 1338. [Abstract] [Full Text] [PDF]

				S. Mukaddam-Daher, A. Menaouar, P.-A. Paquette, M. Jankowski, J. Gutkowska, M.-A. Gillis, Y.-F. Shi, A. Calderone, and J.-C. Tardif Hemodynamic and Cardiac Effects of Chronic Eprosartan and Moxonidine Therapy in Stroke-Prone Spontaneously Hypertensive Rats Hypertension, May 1, 2009; 53(5): 775 - 781. [Abstract] [Full Text] [PDF]

				H. Xia, Y. Feng, T. D. Obr, P. J. Hickman, and E. Lazartigues Angiotensin II Type 1 Receptor-Mediated Reduction of Angiotensin-Converting Enzyme 2 Activity in the Brain Impairs Baroreflex Function in Hypertensive Mice Hypertension, February 1, 2009; 53(2): 210 - 216. [Abstract] [Full Text] [PDF]

				L. Gao, W.-Z. Wang, W. Wang, and I. H. Zucker Imbalance of Angiotensin Type 1 Receptor and Angiotensin II Type 2 Receptor in the Rostral Ventrolateral Medulla: Potential Mechanism for Sympathetic Overactivity in Heart Failure Hypertension, October 1, 2008; 52(4): 708 - 714. [Abstract] [Full Text] [PDF]

				I. H. Zucker Angiotensin-Converting Enzyme 2: A New Player in Central Sympathetic Regulation? Circ. Res., March 28, 2008; 102(6): 628 - 629. [Full Text] [PDF]