on December 29, 2003
Published online before print December 29, 2003, doi: 10.1161/01.HYP.0000111831.50834.93
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 29, 2003
From the Department of Internal Medicine III and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan. * To whom correspondence should be addressed. E-mail: naikai{at}med.kurume-u.ac.jp.
Abstract--Angiotensin II (Ang II) is implicated in the proinflammatory process in various disease situations. Thus, we sought to determine the role of Ang II in early inflammation-induced fibrosis of pressure-overloaded (PO) hearts. PO was induced by suprarenal aortic constriction (AC) at day 0 in male Wistar rats, and they were orally administered 0.1 mg/kg per day candesartan every day from day -7. This was the maximum dose of candesartan that did not change arterial pressure in hypertensive rats with AC (AC rats). In AC rats, cardiac angiotensin-converting enzyme (ACE) activity was transiently enhanced after day 1 and peaked at day 3, declining to lower levels by day 14, whereas serum ACE activity was not changed. In AC rats, PO induced early fibroinflammatory changes (monocyte chemoattractant factor [MCP]-1 and transforming growth factor [TGF]-
Revised on October 31, 2003
Pressure-Independent Effects of Angiotensin II on Hypertensive Myocardial Fibrosis
Keisuke Tokuda;
expression, perivascular macrophage accumulation, and fibroblast proliferation), and thereafter, left ventricular hypertrophy developed, featuring myocyte hypertrophy, intramyocardial arterial wall thickening, and perivascular and interstitial fibroses. Candesartan suppressed the induction of MCP-1 and TGF- and reduced macrophage accumulation and fibroblast proliferation in PO hearts. Candesartan significantly prevented perivascular and interstitial fibrosis. However, candesartan did not affect myocyte hypertrophy and arterial wall thickening. In conclusion, a subdepressor dose of candesartan prevented the MCP-1-mediated inflammatory process and reactive myocardial fibrosis in PO hearts. Ang II might play a key role in reactive fibrosis in hypertensive hearts, independent of arterial pressure changes.
Key words: angiotensin II • fibrosis • hypertension, experimental • macrophages • inflammation
This article has been cited by other articles:
 |
|
 |
|
  J. Lin, X. Zhu, A. R. Chade, K. L. Jordan, R. Lavi, E. Daghini, M. E. Gibson, A. Guglielmotti, A. Lerman, and L. O. Lerman Monocyte Chemoattractant Proteins Mediate Myocardial Microvascular Dysfunction in Swine Renovascular Hypertension Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1810 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kudo, H. Kai, H. Kajimoto, M. Koga, N. Takayama, T. Mori, A. Ikeda, S. Yasuoka, T. Anegawa, H. Mifune, et al. Exaggerated Blood Pressure Variability Superimposed on Hypertension Aggravates Cardiac Remodeling in Rats via Angiotensin II System-Mediated Chronic Inflammation Hypertension, October 1, 2009; 54(4): 832 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Whaley-Connell, J. Habibi, S. A. Cooper, V. G. DeMarco, M. R. Hayden, C. S. Stump, D. Link, C. M. Ferrario, and J. R. Sowers Effect of renin inhibition and AT1R blockade on myocardial remodeling in the transgenic Ren2 rat Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E103 - E109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. L. Nelson, C. T. Robbins, Y. Wu, and H. Granzier Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H366 - H371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Burstein and S. Nattel Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 802 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Whaley-Connell, G. Govindarajan, J. Habibi, M. R. Hayden, S. A. Cooper, Y. Wei, L. Ma, M. Qazi, D. Link, P. R. Karuparthi, et al. Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E355 - E363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Habibi, A. Whaley-Connell, M. A. Qazi, M. R. Hayden, S. A. Cooper, A. Tramontano, J. Thyfault, C. Stump, C. Ferrario, R. Muniyappa, et al. Rosuvastatin, a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Decreases Cardiac Oxidative Stress and Remodeling in Ren2 Transgenic Rats Endocrinology, May 1, 2007; 148(5): 2181 - 2188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Masuyama, T. Tsuruda, J. Kato, T. Imamura, Y. Asada, J.-P. Stasch, K. Kitamura, and T. Eto Soluble Guanylate Cyclase Stimulation on Cardiovascular Remodeling in Angiotensin II-Induced Hypertensive Rats Hypertension, November 1, 2006; 48(5): 972 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saeed, G. Guron, A. Oldfors, B. Lindelow, and H. Herlitz Cardiac fibrosis triggered by the kidney: a case report Nephrol. Dial. Transplant., June 1, 2006; 21(6): 1713 - 1715. [Full Text] [PDF]
|
|
|
|
|
|
S. J. Zieman, V. Melenovsky, and D. A. Kass Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 932 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saito, N. Ishizaka, T. Aizawa, M. Sata, N. Iso-o, E. Noiri, I. Mori, M. Ohno, and R. Nagai Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-{beta}1 in the heart Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1836 - H1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Helske, K. A. Lindstedt, M. Laine, M. Mayranpaa, K. Werkkala, J. Lommi, H. Turto, M. Kupari, and P. T. Kovanen Induction of local angiotensin II-producing systems in stenotic aortic valves J. Am. Coll. Cardiol., November 2, 2004; 44(9): 1859 - 1866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rosenkranz TGF-{beta}1 and angiotensin networking in cardiac remodeling Cardiovasc Res, August 15, 2004; 63(3): 423 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Diez Profibrotic Effects of Angiotensin II in the Heart: A Matter of Mediators Hypertension, June 1, 2004; 43(6): 1164 - 1165. [Full Text] [PDF]
|
|