© 1992 by European Society of Cardiology
Copyright © 1992, European Society of Cardiology
Reactive and reparative myocardial fibrosis in arterial hypertension in the rat
Division of Cardiology, University of Missouri-Columbia, One Hospital Drive, Columbia, MO 65212, USA
Correspondence to Dr Brilla
Objective: Myocardial fibrosis is an important determinant of pathological hypertrophy. In two experimental models of arterial hypertension the purpose of the study was (a) to determine total collagen volume fraction and relative contribution of scarring and perivascular/interstitial fibrosis; and (b) to assess the effects of the aldosterone receptor antagonist spironolactone on these patterns of fibrosis. Methods: 76 eight week old Sprague-Dawley rats weighing 180 to 200 g were used for the studies. Using videodensitometry total collagen volume fraction was separated into the various components for the left and right ventricles in the following experimental models: renovascular hypertension occurring following unilateral renal ischaemia; continuous aldosterone administration via osmotic minipumps with either high (AL) or low (ALLO) sodium diet; renovascular hypertension and AL after pretreatment and continuous treatment with either 20 or 200 mg·kg–1·d–1 subcutaneously of the competitive aldosterone receptor antagonist spironolactone. All groups were compared to age and sex matched controls. Results: After eight weeks, systolic pressure was comparably increased in renovascular hypertension and AL and it remained raised with low dose spironolactone treatment in either model, but was normal with high dose spironolactone or low sodium diet. Left ventricular hypertrophy, expressed as a significant increase in left to right ventricular weight and left ventricle to body weight ratios, was present in renovascular hypertension, AL, and AL + low dose spironolactone compared to control (p<0.005). In either ventricle: (1) the amount of interstitial/perivascular fibrosis and myocardial scarring was increased (p<0.005) in renovascular hypertension and AL compared to control; (2) each was reduced (p<0.005) with either dose of spironolactone; and (3) only scars were seen in ALLO. Conclusions: Myocardial fibrosis of either ventricle was comparable in renovascular hypertension and AL. Spironolactone was able largely to prevent the perivascular/interstitial fibrosis and scarring in either model irrespective of the development of left ventricular hypertrophy and arterial hypertension. Low sodium diet in hyperaldosteronism prevented hypertension and left ventricular hypertrophy, but not scarring. These findings suggest that a rise in plasma aldosterone, relative to sodium intake, may play a role in mediating collagen accumulation in the heart during the development of experimental arterial hypertension.
KEYWORDS hypertension; myocardial fibrosis; aldosterone
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Peters, T. Schluter, T. Riegel, B. S. Peters, A. Beineke, U. Maschke, N. Hosten, J. J. Mullins, and R. Rettig Lack of cardiac fibrosis in a new model of high prorenin hyperaldosteronism Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1845 - H1852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rickard, J. Morgan, G. Tesch, J. W. Funder, P. J. Fuller, and M. J. Young Deletion of Mineralocorticoid Receptors From Macrophages Protects Against Deoxycorticosterone/Salt-Induced Cardiac Fibrosis and Increased Blood Pressure Hypertension, September 1, 2009; 54(3): 537 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Karagiannis, K. Tziomalos, A. I Kakafika, V. G Athyros, F. Harsoulis, and D. P Mikhailidis Medical treatment as an alternative to adrenalectomy in patients with aldosterone-producing adenomas Endocr. Relat. Cancer, September 1, 2008; 15(3): 693 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Costello-Boerrigter, G. Boerrigter, G. J. Harty, A. Cataliotti, M. M. Redfield, and J. C. Burnett Jr Mineralocorticoid Escape by the Kidney But Not the Heart in Experimental Asymptomatic Left Ventricular Dysfunction Hypertension, September 1, 2007; 50(3): 481 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Graham and A. W. Trafford Spatial disruption and enhanced degradation of collagen with the transition from compensated ventricular hypertrophy to symptomatic congestive heart failure Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1364 - H1372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rickard, J. W. Funder, P. J. Fuller, and M. J. Young The Role of the Glucocorticoid Receptor in Mineralocorticoid/Salt-Mediated Cardiac Fibrosis Endocrinology, December 1, 2006; 147(12): 5901 - 5906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Haudek, Y. Xia, P. Huebener, J. M. Lee, S. Carlson, J. R. Crawford, D. Pilling, R. H. Gomer, J. Trial, N. G. Frangogiannis, et al. Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice PNAS, November 28, 2006; 103(48): 18284 - 18289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Arias-Loza, K. Hu, A. Schafer, J. Bauersachs, T. Quaschning, J. Galle, V. Jazbutyte, L. Neyses, G. Ertl, K.-H. Fritzemeier, et al. Medroxyprogesterone Acetate But Not Drospirenone Ablates the Protective Function of 17{beta}-Estradiol in Aldosterone Salt-Treated Rats Hypertension, November 1, 2006; 48(5): 994 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rahman, A. Nishiyama, P. Guo, Y. Nagai, G.-X. Zhang, Y. Fujisawa, Y.-Y. Fan, S. Kimura, N. Hosomi, K. Omori, et al. Effects of Adrenomedullin on Cardiac Oxidative Stress and Collagen Accumulation in Aldosterone-Dependent Malignant Hypertensive Rats J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1323 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Turchin, C. Z. Guo, G. K. Adler, V. Ricchiuti, I. S. Kohane, and G. H. Williams Effect of Acute Aldosterone Administration on Gene Expression Profile in the Heart Endocrinology, July 1, 2006; 147(7): 3183 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benetos, J. P. Gardner, M. Kimura, C. Labat, R. Nzietchueng, B. Dousset, F. Zannad, P. Lacolley, and A. Aviv Aldosterone and Telomere Length in White Blood Cells J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2005; 60(12): 1593 - 1596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Gao, H. Kiriazis, X.-L. Moore, X.-H. Feng, K. Sheppard, A. Dart, and X.-J. Du Regression of pressure overload-induced left ventricular hypertrophy in mice Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2702 - H2707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Milliez, X. Girerd, P.-F. Plouin, J. Blacher, M. E. Safar, and J.-J. Mourad Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1243 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Orlandi, A. Francesconi, M. Marcellini, A. Ferlosio, and L. G. Spagnoli Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit Cardiovasc Res, December 1, 2004; 64(3): 544 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D Struthers Aldosterone blockade in cardiovascular disease Heart, October 1, 2004; 90(10): 1229 - 1234. [Full Text] [PDF]
|
|
|
|
 |
|
 F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [PDF]
|
|
|
|
|
|
C. Sierra and L. M Ruilope Review: Role of the selective aldosterone receptor blockers in arterial hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 23 - 25. [Abstract] [PDF]
|
|
|
|
|
|
A. D Struthers and T. M MacDonald Review of aldosterone- and angiotensin II-induced target organ damage and prevention Cardiovasc Res, March 1, 2004; 61(4): 663 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Mihailidou, M. Mardini, and J. W. Funder Rapid, Nongenomic Effects of Aldosterone in the Heart Mediated by {epsilon} Protein Kinase C Endocrinology, February 1, 2004; 145(2): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Ocaranza, G. Diaz-Araya, J. E. Carreno, D. Munoz, J. P. Riveros, J. E. Jalil, and S. Lavandero Polymorphism in gene coding for ACE determines different development of myocardial fibrosis in rats Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H498 - H506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tokuda, H. Kai, F. Kuwahara, H. Yasukawa, N. Tahara, H. Kudo, K. Takemiya, M. Koga, T. Yamamoto, and T. Imaizumi Pressure-Independent Effects of Angiotensin II on Hypertensive Myocardial Fibrosis Hypertension, February 1, 2004; 43(2): 499 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Williams and G. H. Williams 50th Anniversary of Aldosterone J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2364 - 2372. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Young, L. Moussa, R. Dilley, and J. W. Funder Early Inflammatory Responses in Experimental Cardiac Hypertrophy and Fibrosis: Effects of 11{beta}-Hydroxysteroid Dehydrogenase Inactivation Endocrinology, March 1, 2003; 144(3): 1121 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lacolley, C. Labat, A. Pujol, C. Delcayre, A. Benetos, and M. Safar Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt-Treated Rats: Effects of Eplerenone Circulation, November 26, 2002; 106(22): 2848 - 2853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rocha, A. E. Rudolph, G. E. Frierdich, D. A. Nachowiak, B. K. Kekec, E. A. G. Blomme, E. G. McMahon, and J. A. Delyani Aldosterone induces a vascular inflammatory phenotype in the rat heart Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1802 - H1810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zannad, B. Dousset, and F. Alla Treatment of Congestive Heart Failure: Interfering the Aldosterone-Cardiac Extracellular Matrix Relationship Hypertension, November 1, 2001; 38(5): 1227 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Delyani, E. L. Robinson, and A. E. Rudolph Effect of a selective aldosterone receptor antagonist in myocardial infarction Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H647 - H654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Ammarguellat, I. Larouche, and E. L. Schiffrin Myocardial Fibrosis in DOCA-Salt Hypertensive Rats : Effect of Endothelin ETA Receptor Antagonism Circulation, January 16, 2001; 103(2): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.Y.H Lip, D.C Felmeden, F.L Li-Saw-Hee, and D.G Beevers Hypertensive heart disease. A complex syndrome or a hypertensive 'cardiomyopathy'? Eur. Heart J., October 2, 2000; 21(20): 1653 - 1665. [PDF]
|
|
|
|
|
|
C. G. Brilla, R. C. Funck, and H. Rupp Lisinopril-Mediated Regression of Myocardial Fibrosis in Patients With Hypertensive Heart Disease Circulation, September 19, 2000; 102(12): 1388 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G Brilla Renin-angiotensin-aldosterone system and myocardial fibrosis Cardiovasc Res, July 1, 2000; 47(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
C. G Brilla Regression of myocardial fibrosis in hypertensive heart disease: diverse effects of various antihypertensive drugs Cardiovasc Res, May 1, 2000; 46(2): 324 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mishima, M. Tanimura, G. Suzuki, A. Todor, V. G. Sharov, S. Goldstein, and H. N. Sabbah Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure J. Am. Coll. Cardiol., January 1, 2000; 35(1): 222 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nicoletti and J.-B. Michel Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors Cardiovasc Res, March 1, 1999; 41(3): 532 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Usui, T. Ichiki, M. Katoh, K. Egashira, and A. Takeshita Regulation of Angiotensin II Receptor Expression by Nitric Oxide in Rat Adrenal Gland Hypertension, September 1, 1998; 32(3): 527 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goussev, V. G. Sharov, H. Shimoyama, M. Tanimura, M. Lesch, S. Goldstein, and H. N. Sabbah Effects of ACE inhibition on cardiomyocyte apoptosis in dogs with heart failure Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H626 - H631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fareh, R. M. Touyz, E. L. Schiffrin, and G. Thibault Cardiac Type-1 Angiotensin II Receptor Status in Deoxycorticosterone Acetate–Salt Hypertension in Rats Hypertension, November 1, 1997; 30(5): 1253 - 1259. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Sun, F. J.A Ramires, and K. T Weber Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion Cardiovasc Res, July 1, 1997; 35(1): 138 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benetos, P. Lacolley, and M.E. Safar Prevention of Aortic Fibrosis by Spironolactone in Spontaneously Hypertensive Rats Arterioscler Thromb Vasc Biol, June 1, 1997; 17(6): 1152 - 1156. [Abstract] [Full Text]
|
|
|
|
|
|
C. G. Brilla, L. Matsubara, and K. T. Weber Advanced Hypertensive Heart Disease in Spontaneously Hypertensive Rats: Lisinopril-Mediated Regression of Myocardial Fibrosis Hypertension, August 1, 1996; 28(2): 269 - 275. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Yoshitomi, T. Nishikimi, H. Abe, F. Yoshiwara, T. Suzuki, A. Ashizawa, S. Nagata, M. Kuramochi, H. Matsuoka, and T. Omae Comparison of Changes in Cardiac Structure After Treatment in Secondary Hypertension Hypertension, March 1, 1996; 27(3): 319 - 323. [Abstract] [Full Text]
|
|
|
|
|
|
V. Robert, J.-S. Silvestre, D. Charlemagne, A. Sabri, P. Trouve, M. Wassef, B. Swynghedauw, and C. Delcayre Biological Determinants of Aldosterone-Induced Cardiac Fibrosis in Rats Hypertension, December 1, 1995; 26(6): 971 - 978. [Abstract] [Full Text]
|
|
|
|
|
|
A. Nicoletti, D. Heudes, N. Hinglais, M.-D. Appay, M. Philippe, C. Sassy-Prigent, J. Bariety, and J.-B. Michel Left Ventricular Fibrosis in Renovascular Hypertensive Rats : Effect of Losartan and Spironolactone Hypertension, July 1, 1995; 26(1): 101 - 111. [Abstract] [Full Text]
|
|