Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Circulation. 1999;100:1901-1908

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Boffa, J.-J.
Right arrow Articles by Chatziantoniou, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boffa, J.-J.
Right arrow Articles by Chatziantoniou, C.
Related Collections
Right arrow ACE/Angiotension receptors
Right arrow Genetically altered mice
Right arrow Hypertension - basic studies
Right arrow Endothelium/vascular type/nitric oxide

(Circulation. 1999;100:1901-1908.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Angiotensin II Activates Collagen Type I Gene in the Renal Vasculature of Transgenic Mice During Inhibition of Nitric Oxide Synthesis

Evidence for an Endothelin-Mediated Mechanism

Jean-Jacques Boffa, MD; Pierre-Louis Tharaux, MD; Sandrine Placier, BS; Raymond Ardaillou, MD; Jean-Claude Dussaule, MD, PhD; Christos Chatziantoniou, PhD

From INSERM U.489, Hôpital Tenon, and AP-HP, Laboratoire de Physiologie, Faculté de Médecine St Antoine (J.-C.D.), Paris, France.

Background—Hypertension is frequently associated with renal vascular fibrosis. The purpose of this study was to investigate whether angiotensin II (Ang II) is involved in this fibrogenic process.

Methods and Results—Experiments were performed on transgenic mice harboring the luciferase gene under the control of the collagen I-{alpha}2 chain promoter [procol{alpha}2(I)]. Hypertension was induced by chronic inhibition of NO synthesis (NG-nitro-L-arginine methyl ester, L-NAME). Procol{alpha}2(I) activity started to increase in the renal vasculature after 4 weeks of L-NAME treatment (P<0.01) and at 14 weeks reached 3- and 8-fold increases over control in afferent arterioles and glomeruli, respectively (P<0.001). Losartan, an AT1 receptor antagonist, given simultaneously with L-NAME prevented the increase of procol{alpha}2(I) levels and attenuated the development of renal vascular fibrosis without normalizing systolic pressure increase. Because we found previously that endothelin mediated renal vascular fibrosis in the L-NAME model, the interaction between Ang II, endothelin, and procol{alpha}2(I) was investigated in ex vivo and short-term in vivo experiments. In both conditions, the Ang II–induced activation of procol{alpha}2(I) in renal cortex was blocked by an endothelin receptor antagonist.

Conclusions—During chronic inhibition of NO, the collagen I gene becomes activated, leading to the development of renal vascular fibrosis. Ang II is a major player in this fibrogenic process, and its effect on collagen I gene is independent of systemic hemodynamics and is at least partly mediated by the profibrogenic action of endothelin.


Key Words: hypertension • kidney • collagen • angiotensin • endothelin




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
S. J. An, R. Boyd, M. Zhu, A. Chapman, D. R. Pimentel, and H. D. Wang
NADPH oxidase mediates angiotensin II-induced endothelin-1 expression in vascular adventitial fibroblasts
Cardiovasc Res, September 1, 2007; 75(4): 702 - 709.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
S. Placier, J.-J. Boffa, J.-C. Dussaule, and C. Chatziantoniou
Reversal of renal lesions following interruption of nitric oxide synthesis inhibition in transgenic mice
Nephrol. Dial. Transplant., April 1, 2006; 21(4): 881 - 888.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. J. An, R. Boyd, Y. Wang, X. Qiu, and H. D. Wang
Endothelin-1 expression in vascular adventitial fibroblasts
Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H700 - H708.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
C. Chatziantoniou and J.-C. Dussaule
Insights into the mechanisms of renal fibrosis: is it possible to achieve regression?
Am J Physiol Renal Physiol, August 1, 2005; 289(2): F227 - F234.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Sarkar, E. Vellaichamy, D. Young, and S. Sen
Influence of cytokines and growth factors in ANG II-mediated collagen upregulation by fibroblasts in rats: role of myocytes
Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H107 - H117.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. C. Katwa
Cardiac myofibroblasts isolated from the site of myocardial infarction express endothelin de novo
Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1132 - H1139.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J.-J. Boffa, Y. Lu, S. Placier, A. Stefanski, J.-C. Dussaule, and C. Chatziantoniou
Regression of Renal Vascular and Glomerular Fibrosis: Role of Angiotensin II Receptor Antagonism and Matrix Metalloproteinases
J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1132 - 1144.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. G. F. Bronzwaer, C. Heymes, C. A. Visser, and W. J. Paulus
Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy
Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H10 - H16.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Fakhouri, S. Placier, R. Ardaillou, J.-C. Dussaule, and C. Chatziantoniou
Angiotensin II Activates Collagen Type I Gene in the Renal Cortex and Aorta of Transgenic Mice through Interaction with Endothelin and TGF-{beta}
J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2701 - 2710.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
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]

Home page
 HypertensionHome page
H. D. Intengan and E. L. Schiffrin
Vascular Remodeling in Hypertension: Roles of Apoptosis, Inflammation, and Fibrosis
Hypertension, September 1, 2001; 38(3): 581 - 587.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. Kaikita, A. B. Fogo, L. Ma, J. A. Schoenhard, N. J. Brown, and D. E. Vaughan
Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition
Circulation, August 14, 2001; 104(7): 839 - 844.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. Dechend, A. Fiebeler, J.-K. Park, D. N. Muller, J. Theuer, E. Mervaala, M. Bieringer, D. Gulba, R. Dietz, F. C. Luft, et al.
Amelioration of Angiotensin II-Induced Cardiac Injury by a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor
Circulation, July 31, 2001; 104(5): 576 - 581.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. INIGO, J. M. CAMPISTOL, S. LARIO, C. PIERA, B. CAMPOS, M. BESCOS, F. OPPENHEIMER, and F. RIVERA
Effects of Losartan and Amlodipine on Intrarenal Hemodynamics and TGF-{beta}1 Plasma Levels in a Crossover Trial in Renal Transplant Recipients
J. Am. Soc. Nephrol., April 1, 2001; 12(4): 822 - 827.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J.-C. DUSSAULE, P.-L. THARAUX, J.-J. BOFFA, F. FAKHOURI, R. ARDAILLOU, and C. CHATZIANTONIOU
Mechanisms Mediating the Renal Profibrotic Actions of Vasoactive Peptides in Transgenic Mice
J. Am. Soc. Nephrol., November 1, 2000; 11(90002): 124S - 128.
[Abstract] [Full Text]


Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 1999 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.