This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Moore, A. F. Articles by Carey, R. M. Search for Related Content PubMed PubMed Citation Articles by Moore, A. F. Articles by Carey, R. M. Related Collections ACE/Angiotension receptors Other hypertension Hypertension - basic studies

(Hypertension. 2001;37:1285.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Selective Inhibition of the Renal Angiotensin Type 2 Receptor Increases Blood Pressure in Conscious Rats

Allan F. Moore; Nicolas T. Heiderstadt; Esther Huang; Nancy L. Howell; Zhi-Qin Wang; Helmy M. Siragy; Robert M. Carey

From the Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville.

Abstract—The angiotensin II type 2 (AT₂) receptor is present in rat kidney; however, its function is not well understood. The purpose of this study was to evaluate the role of the AT₂ receptor in blood pressure (BP) regulation. The effects of selective inhibition of the renal AT₂ receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) were examined in conscious uninephrectomized rats. Oligodeoxynucleotides (AS-ODN or scrambled [S-ODN]) were infused directly into the renal interstitial space by using an osmotic pump at 1 µL/h for 7 days. Texas red–labeled AS-ODN was distributed in renal tubules in the infused but not the contralateral kidney of normal rats. Continuous renal interstitial infusion of the AS-ODN, but not S-ODN, caused a significant (P<0.01) increase in BP 1 to 5 days after the initiation of the infusion. AS-ODN–treated rats experienced an increase in systolic BP from 109±4 to 130±4 mm Hg (n=8, P<0.01), whereas S-ODN–treated (n=8) and vehicle-treated (n=8) rats did not show any significant change in BP. On day 5 of the oligodeoxynucleotide infusion, AS-ODN–treated rats exhibited a greater pressor response to systemic angiotensin II infusion (30 ng/kg per hour) than did S-ODN–treated rats (P<0.01). Renal interstitial fluid cGMP decreased from 11.9±0.8 to 3.6±0.5 pmol/mL (P<0.001), and bradykinin decreased from 0.05±0.05 to 0.18±0.03 ng/mL (P<0.001) in response to AS-ODN, but they were not significantly changed in response to S-ODN. To evaluate the effects of AS-ODN and S-ODN on AT₂ receptor expression, Western Blot analysis was performed on treated kidneys. Kidneys treated with AS-ODN had 40% less expression of AT₂ receptor than did kidneys treated with S-ODN or vehicle (P<0.05). These results suggest that AS-ODN directed selectively against the renal AT₂ receptor decreased receptor expression and caused an increase in BP. We conclude that the renal AT₂ receptor plays an important role in the regulation of BP via a bradykinin/cGMP vasodilator signaling cascade.

Key Words: blood pressure • receptors, angiotensin II • hypertension, experimental • kidney • rats

This article has been cited by other articles:

				A. H. Siddiqui, Q. Ali, and T. Hussain Protective Role of Angiotensin II Subtype 2 Receptor in Blood Pressure Increase in Obese Zucker Rats Hypertension, February 1, 2009; 53(2): 256 - 261. [Abstract] [Full Text] [PDF]

				T. A. Barker, M. P. Massett, V. A. Korshunov, A. M. Mohan, A. J. Kennedy, and B. C. Berk Angiotensin II Type 2 Receptor Expression After Vascular Injury: Differing Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade Hypertension, November 1, 2006; 48(5): 942 - 949. [Abstract] [Full Text] [PDF]

				S. McMullen and S. C. Langley-Evans Sex-Specific Effects of Prenatal Low-Protein and Carbenoxolone Exposure on Renal Angiotensin Receptor Expression in Rats Hypertension, December 1, 2005; 46(6): 1374 - 1380. [Abstract] [Full Text] [PDF]

				S. Guimaraes and H. Pinheiro Functional evidence that in the cardiovascular system AT1 angiotensin II receptors are AT1B prejunctionally and AT1A postjunctionally Cardiovasc Res, August 1, 2005; 67(2): 208 - 215. [Abstract] [Full Text] [PDF]

				S. McMullen and S. C. Langley-Evans Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R85 - R90. [Abstract] [Full Text] [PDF]

				H. Gong, Y.-X. Wang, Y.-Z. Zhu, W.-W. Wang, M.-J. Wang, T. Yao, and Y.-C. Zhu Cellular distribution of GPR14 and the positive inotropic role of urotensin II in the myocardium in adult rat J Appl Physiol, December 1, 2004; 97(6): 2228 - 2235. [Abstract] [Full Text] [PDF]

				S. Olson, R. Oeckler, X. Li, L. Du, F. Traganos, X. Zhao, and T. Burke-Wolin Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L559 - L568. [Abstract] [Full Text] [PDF]

				V. M. Vehaskari, T. Stewart, D. Lafont, C. Soyez, D. Seth, and J. Manning Kidney angiotensin and angiotensin receptor expression in prenatally programmed hypertension Am J Physiol Renal Physiol, August 1, 2004; 287(2): F262 - F267. [Abstract] [Full Text] [PDF]

				H. Wang, S. Gallinat, H.-w. Li, C. Sumners, M. K. Raizada, and M. J. Katovich Elevated blood pressure in normotensive rats produced by 'knockdown' of the angiotensin type 2 receptor Exp Physiol, May 1, 2004; 89(3): 313 - 322. [Abstract] [Full Text] [PDF]

				X.-H. Jin, H. E. McGrath, J. J. Gildea, H. M. Siragy, R. A. Felder, and R. M. Carey Renal Interstitial Guanosine Cyclic 3', 5'-Monophosphate Mediates Pressure-Natriuresis Via Protein Kinase G Hypertension, May 1, 2004; 43(5): 1133 - 1139. [Abstract] [Full Text] [PDF]

				B. T. Andresen, G. G. Romero, and E. K. Jackson AT2 Receptors Attenuate AT1 Receptor-Induced Phospholipase D Activation in Vascular Smooth Muscle Cells J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 425 - 431. [Abstract] [Full Text]

				H. Cai, Z. Li, S. Dikalov, S. M. Holland, J. Hwang, H. Jo, S. C. Dudley Jr., and D. G. Harrison NAD(P)H Oxidase-derived Hydrogen Peroxide Mediates Endothelial Nitric Oxide Production in Response to Angiotensin II J. Biol. Chem., December 6, 2002; 277(50): 48311 - 48317. [Abstract] [Full Text] [PDF]

				L. Cervenka, V. Horacek, I. Vaneckova, J. A. Hubacek, M. I. Oliverio, T. M. Coffman, and L. G. Navar Essential Role of AT1A Receptor in the Development of 2K1C Hypertension Hypertension, November 1, 2002; 40(5): 735 - 741. [Abstract] [Full Text] [PDF]

				S. P. Bagby, L. S. LeBard, Z. Luo, B. E. Ogden, C. Corless, E. D. McPherson, and R. C. Speth ANG II AT1 and AT2 receptors in developing kidney of normal microswine Am J Physiol Renal Physiol, October 1, 2002; 283(4): F755 - F764. [Abstract] [Full Text] [PDF]

				C. Berry, R. Touyz, A. F. Dominiczak, R. C. Webb, and D. G. Johns Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2337 - H2365. [Abstract] [Full Text] [PDF]