From the Division of Hypertension and Vascular Medicine, University of
Lausanne Medical School (L.M., J.N., J.-F.A., D.B.B., H.R.B., T.P.), and the
Department of Pathology, University of Geneva Medical School (G.G.),
Switzerland.
Correspondence to Thierry Pedrazzini, Division of Hypertension and Vascular Medicine, University of Lausanne Medical School, CH-1011 Lausanne, Switzerland. E-mail Thierry.Pedrazzini{at}chuv.hospvd.ch
Abstract—Cardiac
hypertrophy is frequent in chronic hypertension. The
renin-angiotensin system, via its effector
angiotensin II (Ang II), regulates blood pressure and
participates in sustaining hypertension. In addition, a growing body of
evidence indicates that Ang II acts also as a growth factor. However,
it is still a matter of debate whether the trophic effect of Ang II can
trigger cardiac hypertrophy in the absence of elevated
blood pressure. To address this question, transgenic mice
overexpressing the rat angiotensinogen gene, specifically
in the heart, were generated to increase the local activity of the
renin-angiotensin system and therefore Ang II
production. These mice develop myocardial
hypertrophy without signs of fibrosis independently from
the presence of hypertension, demonstrating that local Ang II
production is important in mediating the hypertrophic response
in vivo.
© 1998 American Heart Association, Inc.
Scientific Contributions
Blood Pressure–Independent Cardiac Hypertrophy Induced by Locally Activated Renin-Angiotensin System
Key Words: heart • hypertrophy • renin • angiotensinogen • mice, transgenic
This article has been cited by other articles:
 |
|
 |
|
  K. Gusev, A. A. Domenighetti, L. M.D. Delbridge, T. Pedrazzini, E. Niggli, and M. Egger Angiotensin II-Mediated Adaptive and Maladaptive Remodeling of Cardiomyocyte Excitation-Contraction Coupling Circ. Res., July 2, 2009; 105(1): 42 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Huggins, C. L. Curl, R. Patel, P. L. McLennan, M. L. Theiss, T. Pedrazzini, S. Pepe, and L. M. D. Delbridge Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H957 - H966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Croquelois, A. A. Domenighetti, M. Nemir, M. Lepore, N. Rosenblatt-Velin, F. Radtke, and T. Pedrazzini Control of the adaptive response of the heart to stress via the Notch1 receptor pathway J. Exp. Med., December 22, 2008; 205(13): 3173 - 3185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Rivard, P. Paradis, M. Nemer, and C. Fiset Cardiac-specific overexpression of the human type 1 angiotensin II receptor causes delayed repolarization Cardiovasc Res, April 1, 2008; 78(1): 53 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Xiao, S. Fuchs, E. A. Bernstein, P. Li, D. J. Campbell, and K. E. Bernstein Mice expressing ACE only in the heart show that increased cardiac angiotensin II is not associated with cardiac hypertrophy Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H659 - H667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. W. van den Brink, L. M D. Delbridge, T. Pedrazzini, F. L Rosenfeldt, and S. Pepe Augmented myocardial methionine-enkephalin in a murine model of cardiac angiotensin II-overexpression Journal of Renin-Angiotensin-Aldosterone System, December 1, 2007; 8(4): 153 - 159. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Kilic, A. Bubikat, B. Gassner, H. A. Baba, and M. Kuhn Local Actions of Atrial Natriuretic Peptide Counteract Angiotensin II Stimulated Cardiac Remodeling Endocrinology, September 1, 2007; 148(9): 4162 - 4169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, O. A. Carretero, C.-X. Lin, M. A. Cavasin, E. G. Shesely, J. J. Yang, T. L. Reudelhuber, and X.-P. Yang Role of cardiac overexpression of ANG II in the regulation of cardiac function and remodeling postmyocardial infarction Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1900 - H1907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Reudelhuber, K. E. Bernstein, and P. Delafontaine Is Angiotensin II a Direct Mediator of Left Ventricular Hypertrophy?: Time for Another Look Hypertension, June 1, 2007; 49(6): 1196 - 1201. [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. J. Silva, E. D. Moreira, A. C. Pereira, J. G. Mill, E. M. Krieger, and J. E. Krieger ACE gene dosage modulates pressure-induced cardiac hypertrophy in mice and men Physiol Genomics, November 21, 2006; 27(3): 237 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brand, N. Lamande, C. D. Sigmund, E. Larger, P. Corvol, and J.-M. Gasc Angiotensinogen Modulates Renal Vasculature Growth Hypertension, June 1, 2006; 47(6): 1067 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Michalik, J. N. Feige, L. Gelman, T. Pedrazzini, H. Keller, B. Desvergne, and W. Wahli Selective Expression of a Dominant-Negative Form of Peroxisome Proliferator-Activated Receptor in Keratinocytes Leads to Impaired Epidermal Healing Mol. Endocrinol., September 1, 2005; 19(9): 2335 - 2348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Domenighetti, Q. Wang, M. Egger, S. M. Richards, T. Pedrazzini, and L. M.D. Delbridge Angiotensin II-Mediated Phenotypic Cardiomyocyte Remodeling Leads to Age-Dependent Cardiac Dysfunction and Failure Hypertension, August 1, 2005; 46(2): 426 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Bernstein, H. D. Xiao, K. Frenzel, P. Li, X. Z. Shen, J. W. Adams, and S. Fuchs Six Truisms Concerning ACE and the Renin-Angiotensin System Educed From the Genetic Analysis of Mice Circ. Res., June 10, 2005; 96(11): 1135 - 1144. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Xiang, J. Kong, S. Chen, L.-P. Cao, G. Qiao, W. Zheng, W. Liu, X. Li, D. G. Gardner, and Y. C. Li Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E125 - E132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R Porrello, C. E Huggins, C. L Curl, A. A Domenighetti, T. Pedrazzini, L. M. Delbridge, and T. O Morgan Elevated dietary sodium intake exacerbates myocardial hypertrophy associated with cardiac-specific overproduction of angiotensin II Journal of Renin-Angiotensin-Aldosterone System, December 1, 2004; 5(4): 169 - 175. [Abstract] [PDF]
|
|
|
|
 |
|
 H. D. Xiao, S. Fuchs, D. J. Campbell, W. Lewis, S. C. Dudley Jr, V. S. Kasi, B. D. Hoit, G. Keshelava, H. Zhao, M. R. Capecchi, et al. Mice with Cardiac-Restricted Angiotensin-Converting Enzyme (ACE) Have Atrial Enlargement, Cardiac Arrhythmia, and Sudden Death Am. J. Pathol., September 1, 2004; 165(3): 1019 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. De Mello and J. Monterrubio Intracellular and Extracellular Angiotensin II Enhance the L-Type Calcium Current in the Failing Heart Hypertension, September 1, 2004; 44(3): 360 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. FitzGerald, B. A. Murray, and D. J. Walsh Hypotensive Peptides from Milk Proteins J. Nutr., April 1, 2004; 134(4): 980S - 988S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Campbell, T. Alexiou, H. D. Xiao, S. Fuchs, M. J. McKinley, P. Corvol, and K. E. Bernstein Effect of Reduced Angiotensin-Converting Enzyme Gene Expression and Angiotensin-Converting Enzyme Inhibition on Angiotensin and Bradykinin Peptide Levels in Mice Hypertension, April 1, 2004; 43(4): 854 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E Huggins, A. A Domenighetti, T. Pedrazzini, S. Pepe, and L. M. Delbridge Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 186 - 190. [Abstract] [PDF]
|
|
|
|
 |
|
 D. L. Brutsaert Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity Physiol Rev, January 1, 2003; 83(1): 59 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. van Kats, D. Methot, P. Paradis, D. W. Silversides, and T. L. Reudelhuber Use of a Biological Peptide Pump to Study Chronic Peptide Hormone Action in Transgenic Mice. DIRECT AND INDIRECT EFFECTS OF ANGIOTENSIN II ON THE HEART J. Biol. Chem., November 16, 2001; 276(47): 44012 - 44017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Engeli, R. Negrel, and A. M. Sharma Physiology and Pathophysiology of the Adipose Tissue Renin-Angiotensin System Hypertension, June 1, 2000; 35(6): 1270 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. FINK, S. ERGÜN, D. KRALISCH, U. REMMERS, J. WEIL, and T. ESCHENHAGEN Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement FASEB J, April 1, 2000; 14(5): 669 - 679. [Abstract] [Full Text]
|
|
|
|
|
|
L. Mazzolai, T. Pedrazzini, F. Nicoud, G. Gabbiani, H.-R. Brunner, and J. Nussberger Increased Cardiac Angiotensin II Levels Induce Right and Left Ventricular Hypertrophy in Normotensive Mice Hypertension, April 1, 2000; 35(4): 985 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Katz, J. A. Opsahl, S. E. Wernsing, L. M. Forbis, J. Smith, and L. J. Heller Myocardial renin is neither necessary nor sufficient to initiate or maintain ventricular hypertrophy Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2000; 278(3): R578 - R586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meneton, I. Ichikawa, T. Inagami, and J. Schnermann Renal physiology of the mouse Am J Physiol Renal Physiol, March 1, 2000; 278(3): F339 - F351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mervaala, D. N. Muller, F. Schmidt, J.-K. Park, V. Gross, M. Bader, V. Breu, D. Ganten, H. Haller, and F. C. Luft Blood Pressure-Independent Effects in Rats With Human Renin and Angiotensinogen Genes Hypertension, February 1, 2000; 35(2): 587 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Paradis, N. Dali-Youcef, F. W. Paradis, G. Thibault, and M. Nemer Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling PNAS, January 18, 2000; 97(2): 931 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Madeddu, C. Emanueli, R. Maestri, M. B. Salis, A. Minasi, M. C. Capogrossi, and G. Olivetti Angiotensin II Type 1 Receptor Blockade Prevents Cardiac Remodeling in Bradykinin B2 Receptor Knockout Mice Hypertension, January 1, 2000; 35(1): 391 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Emanueli, R. Maestri, D. Corradi, R. Marchione, A. Minasi, M. G. Tozzi, M. B. Salis, S. Straino, M. C. Capogrossi, G. Olivetti, et al. Dilated and Failing Cardiomyopathy in Bradykinin B2 Receptor Knockout Mice Circulation, December 7, 1999; 100(23): 2359 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Dostal and K. M. Baker The Cardiac Renin-Angiotensin System : Conceptual, or a Regulator of Cardiac Function? Circ. Res., October 1, 1999; 85(7): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L Kuroski de Bold Estrogen, natriuretic peptides and the renin-angiotensin system Cardiovasc Res, March 1, 1999; 41(3): 524 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Luft, E. Mervaala, D. N. Muller, V. Gross, F. Schmidt, J. K. Park, C. Schmitz, A. Lippoldt, V. Breu, R. Dechend, et al. Hypertension-Induced End-Organ Damage : A New Transgenic Approach to an Old Problem Hypertension, January 1, 1999; 33(1): 212 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Muller, K. F. Hilgers, S. Mathews, V. Breu, W. Fischli, R. Uhlmann, and F. C. Luft Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen Hypertension, January 1, 1999; 33(1): 312 - 317. [Abstract] [Full Text] [PDF]
|
|