| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 1995;25:98-104.)
© 1995 American Heart Association, Inc.
Articles |
Myocardial Remodeling in Hypertensive Ren-2 Transgenic Rats
From the Departments of Medicine (F.J.V., J.H.O., W.H.D.) and Bioengineering (D.A.M.), University of California at San Diego, La Jolla.
Abstract Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin. We determined the extent of left ventricular remodeling present in Ren-2 rats at 16 weeks of age by measuring blood pressure, ratio of heart weight to body weight, left ventricular wall thickness, passive (diastolic) left ventricular compliance, and left ventricular collagen content using hydroxyproline and collagen area fraction. Changes in perivascular fibronectin and collagen type I and III were examined with immunohistochemistry. Blood pressure values at time of death were 244±15 mm Hg for Ren-2 rats (mean±SD, n=5). Ratios of heart weight to body weight (grams per kilogram) for Ren-2 animals were 4.1±0.2 versus 3.1±0.1 for controls (n=6, P<.001). Wall thickness values for control animals were 2.6±0.1 versus 4.1±0.4 mm for Ren-2 animals (P<.001). Left ventricular Ren-2 hydroxyproline measurements were significantly decreased (3.4±0.2 versus 4.7±0.9 mg/g dry wt for controls). Significant decreases of approximately 30% were also observed in collagen area fraction in Ren-2 rats. Immunohistochemical and picrosirius red staining indicated increased amounts of perivascular fibrosis in all Ren-2 animals (when compared with controls) with enhanced levels of perivascular fibronectin and type I and type III collagen proteins. Left ventricular compliance measurements indicated a decrease in left ventricular volume for all left ventricular pressures (P=.07). In conclusion, Ren-2 animals at 16 weeks of age demonstrated a substantial degree of cardiac hypertrophy that was accompanied by perivascular but not diffuse fibrosis and a stiffened left ventricle.
Key Words: angiotensin II • fibrosis • extracellular matrix • transforming growth factor-ß • compliance
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 K. Venkatachalam, S. Mummidi, D. M. Cortez, S. D. Prabhu, A. J. Valente, and B. Chandrasekar Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2078 - H2087. [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. Peng, O. A. Carretero, D. R. Brigstock, N. Oja-Tebbe, and N.-E. Rhaleb Ac-SDKP Reverses Cardiac Fibrosis in Rats With Renovascular Hypertension Hypertension, December 1, 2003; 42(6): 1164 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Seccia, A. S. Belloni, R. Kreutz, M. Paul, G. G. Nussdorfer, A. C. Pessina, and G. P. Rossi Cardiac fibrosis occurs early and involves endothelin and AT-1 receptors in hypertension due to endogenous angiotensin II J. Am. Coll. Cardiol., February 19, 2003; 41(4): 666 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Akiyama-Uchida, N. Ashizawa, A. Ohtsuru, S. Seto, T. Tsukazaki, H. Kikuchi, S. Yamashita, and K. Yano Norepinephrine Enhances Fibrosis Mediated by TGF-{beta} in Cardiac Fibroblasts Hypertension, August 1, 2002; 40(2): 148 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Zolk, J. Quattek, U. Seeland, A. El-Armouche, T. Eschenhagen, and M. Bohm Activation of the cardiac endothelin system in left ventricular hypertrophy before onset of heart failure in TG(mREN2)27 rats Cardiovasc Res, February 1, 2002; 53(2): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Pinto, S.-J. Pinto-Sietsma, T. Philipp, S. Engler, P. Ko{beta}mehl, B. Hocher, H. Marquardt, S. Sethmann, R. Lauster, H.-J. Merker, et al. Reduction in Left Ventricular Messenger RNA for Transforming Growth Factor {beta}1 Attenuates Left Ventricular Fibrosis and Improves Survival Without Lowering Blood Pressure in the Hypertensive TGR(mRen2)27 Rat Hypertension, November 1, 2000; 36(5): 747 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rothermund, Y. M. Pinto, B. Hocher, R. Vetter, S. Leggewie, P. Ko{beta}mehl, H.-D. Orzechowski, R. Kreutz, and M. Paul Cardiac Endothelin System Impairs Left Ventricular Function in Renin-Dependent Hypertension via Decreased Sarcoplasmic Reticulum Ca2+ Uptake Circulation, September 26, 2000; 102(13): 1582 - 1588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Bishop, L. A. Kiernan, H. E. Montgomery, P. Gohlke, and J. R. McEwan Raised blood pressure, not renin-angiotensin systems, causes cardiac fibrosis in TGR m(Ren2)27 rats Cardiovasc Res, July 1, 2000; 47(1): 57 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Flesch, F. Schiffer, O. Zolk, Y. Pinto, S. Rosenkranz, C. Hirth-Dietrich, G. Arnold, M. Paul, and M. Bohm Contractile Systolic and Diastolic Dysfunction in Renin-Induced Hypertensive Cardiomyopathy Hypertension, September 1, 1997; 30(3): 383 - 391. [Abstract] [Full Text]
|
|
|
|
|
|
M. Marttila, O. Vuolteenaho, D. Ganten, K. Nakao, and H. Ruskoaho Synthesis and Secretion of Natriuretic Peptides in the Hypertensive TGR(mREN-2)27 Transgenic Rat Hypertension, December 1, 1996; 28(6): 995 - 1004. [Abstract] [Full Text]
|
|