This Article Full Text 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 Chansel, D. Articles by Ardaillou, R. Search for Related Content PubMed PubMed Citation Articles by Chansel, D. Articles by Ardaillou, R.

(Hypertension. 1996;27:867-874.)
© 1996 American Heart Association, Inc.

Articles

Regulation of Angiotensin II Receptor Subtypes by Dexamethasone in Rat Mesangial Cells

Dominique Chansel; Catherine Llorens-Cortes; Sophie Vandermeersch; Paul Pham; Raymond Ardaillou

From INSERM 64, Hôpital Tenon (D.C., S.V., R.A.); INSERM 36, Collège de France (C.L.-C.), Paris; and Centre d'Etudes Nucleaires Saclay, Gif-sur-Yvette (P.P.), France.

Correspondence to Raymond Ardaillou, Hôpital Tenon, 4 Rue de la Chine, 75020 Paris, France.

Abstract The objective of this study was to examine the role of dexamethasone on the expression of angiotensin II (Ang II) receptors in cultured rat mesangial cells. Dexamethasone caused concentration- and time-dependent decreases in ¹²⁵I–[Sar¹,Ala⁸]Ang II binding that were prevented by glucocorticoid receptor inhibition with mifepristone. A lag time of 24 hours and a dexamethasone concentration of at least 10 nmol/L were necessary for this effect to occur. Dexamethasone-induced reduction of ¹²⁵I–[Sar¹,Ala⁸]Ang II binding resulted from decreased Ang II type 1 (AT₁) receptor density. No change in the apparent dissociation constant was observed. Dexamethasone also markedly inhibited Ang II–dependent inositol phosphate accumulation. Both reverse transcription–polymerase chain reaction and Northern blot analysis using specific short probes from the 3' noncoding region of the cDNA demonstrated the presence of AT_1A and AT_1B receptor mRNAs in rat mesangial cells, with a slight predominance of AT_1B. Therefore, we studied the effect of dexamethasone on the expression of these two subtypes in rat mesangial cells. Dexamethasone produced a time-dependent decrease of AT_1B receptor mRNA that was apparent after 6 hours of incubation, whereas AT_1A receptor mRNA did not change. Mifepristone also suppressed the dexamethasone-induced decrease in AT_1B receptor mRNA. In conclusion, glucocorticoids diminish Ang II receptor density at the mesangial cell surface through a mechanism that implies successive interaction with the glucocorticoid receptor and specific reduction in AT_1B receptor mRNA expression. This differential regulation of both AT₁ receptor subtypes might allow glucocorticoids to exert adjusted effects in their various target tissues.

Key Words: receptors, angiotensin II • rat • mesangial cells • dexamethasone • mifepristone

This article has been cited by other articles:

				I. G Bogdarina, P. J King, and A. J L Clark Characterization of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids J. Mol. Endocrinol., August 1, 2009; 43(2): 73 - 80. [Abstract] [Full Text] [PDF]

				R. R. Singh, K. M. Moritz, J. F. Bertram, and L. A. Cullen-McEwen Effects of dexamethasone exposure on rat metanephric development: in vitro and in vivo studies Am J Physiol Renal Physiol, August 1, 2007; 293(2): F548 - F554. [Abstract] [Full Text] [PDF]

				S. Y. Park, C. Y. Song, B. C. Kim, H. K. Hong, and H. S. Lee Angiotensin II mediates LDL-induced superoxide generation in mesangial cells Am J Physiol Renal Physiol, November 1, 2003; 285(5): F909 - F915. [Abstract] [Full Text] [PDF]

				A. Hus-Citharel, N. Bouby, J. Marchetti, D. Chansel, D. Goidin, D. Gourdji, P. Corvol, and C. Llorens-Cortes Desensitization of Type 1 Angiotensin II Receptor Subtypes in the Rat Kidney Endocrinology, November 1, 2001; 142(11): 4683 - 4692. [Abstract] [Full Text] [PDF]

				C.-B. Lanz, M. Causevic, C. Heiniger, F. J. Frey, B. M. Frey, and M. G. Mohaupt Fluid Shear Stress Reduces 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Hypertension, January 1, 2001; 37(1): 160 - 169. [Abstract] [Full Text] [PDF]

				J. Schwobel, T. Fischer, B. Lanz, and M. Mohaupt Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1092 - F1100. [Abstract] [Full Text] [PDF]

				F. Amiri and R. Garcia Regulation of angiotensin II receptors and PKC isoforms by glucose in rat mesangial cells Am J Physiol Renal Physiol, May 1, 1999; 276(5): F691 - F699. [Abstract] [Full Text] [PDF]

				Z. Zhu, S. H. Zhang, C. Wagner, A. Kurtz, N. Maeda, T. Coffman, and W. J. Arendshorst Angiotensin AT1B Receptor Mediates Calcium Signaling in Vascular Smooth Muscle Cells of AT1A Receptor–Deficient Mice Hypertension, May 1, 1998; 31(5): 1171 - 1177. [Abstract] [Full Text] [PDF]