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 Ichiki, T. Articles by Takeshita, A. Search for Related Content PubMed PubMed Citation Articles by Ichiki, T. Articles by Takeshita, A. Related Collections ACE/Angiotension receptors

(Hypertension. 2001;37:535.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Reactive Oxygen Species–Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor mRNA by Angiotensin II

Toshihiro Ichiki; Kotaro Takeda; Tomotake Tokunou; Yuko Funakoshi; Kiyoko Ito; Naoko Iino; Akira Takeshita

From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Correspondence to Toshihiro Ichiki, MD, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan. E-mail ichiki{at}cardiol.med.kyushu-u.ac.jp

Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of angiotensin (Ang) II through Ang II type 1 receptor (AT₁-R). However, the role of ROS in the regulation of AT₁-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT₁-R by Ang II. Ang II (10^-6 mol/L) decreased AT₁-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells. Preincubation of vascular smooth muscle cells with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II–induced downregulation of AT₁-R mRNA. The effect of NAC was due to stabilization of the AT₁-R mRNA that was destabilized by Ang II. The Ang II–induced AT₁-R mRNA downregulation was also blocked by PD98059, an extracellular signal–regulated protein kinase (ERK) kinase inhibitor. Ang II–induced ERK activation was inhibited by NAC as well as by PD98059. Exogenous H₂O₂ also suppressed AT₁-R mRNA. These results suggest that the production of ROS and the activation of ERK are critical for the downregulation of AT₁-R mRNA. The generation of ROS through stimulation of AT₁-R not only mediates signaling of Ang II but also may play a crucial role in the adaptation process of AT₁-R to the sustained stimulation of Ang II.

Key Words: receptor, angiotensin II • reactive oxygen species • protein kinases

This article has been cited by other articles:

				M. E. Ullian, A. K. Gelasco, W. R. Fitzgibbon, C. N. Beck, and T. A. Morinelli N-Acetylcysteine Decreases Angiotensin II Receptor Binding in Vascular Smooth Muscle Cells J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2346 - 2353. [Abstract] [Full Text] [PDF]

				M. Akishita, K. Nagai, H. Xi, W. Yu, N. Sudoh, T. Watanabe, M. Ohara-Imaizumi, S. Nagamatsu, K. Kozaki, M. Horiuchi, et al. Renin-Angiotensin System Modulates Oxidative Stress-Induced Endothelial Cell Apoptosis in Rats Hypertension, June 1, 2005; 45(6): 1188 - 1193. [Abstract] [Full Text] [PDF]

				A. A Voors, P. P van Geel, M. Oosterga, H. Buikema, D. J van Veldhuisen, and W. H van Gilst Vascular effects of quinapril completely depend on ACE insertion/deletion polymorphism Journal of Renin-Angiotensin-Aldosterone System, September 1, 2004; 5(3): 130 - 134. [Abstract] [PDF]

				F. S. Gragasin, Y. Xu, I. A. Arenas, N. Kainth, and S. T. Davidge Estrogen Reduces Angiotensin II-Induced Nitric Oxide Synthase and NAD(P)H Oxidase Expression in Endothelial Cells Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 38 - 44. [Abstract] [Full Text] [PDF]

				Y. Xu, D. Kumar, J. R. B. Dyck, W. R. Ford, A. S. Clanachan, G. D. Lopaschuk, and B. I. Jugdutt AT1 and AT2 receptor expression and blockade after acute ischemia-reperfusion in isolated working rat hearts Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1206 - H1215. [Abstract] [Full Text] [PDF]