(Hypertension. 1999;33:816-822.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Endothelin System–Dependent Cardiac Remodeling in Renovascular Hypertension
From the Department of Nephrology, Universitätsklinikum Charité der Humboldt Universität zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany.
Correspondence to PD Dr Berthold Hocher, Universitätsklinikum Charité der Humboldt Universität zu Berlin, Abteilung für Nephrologie, Schumannstrasse 20-21, 10098 Berlin, Germany. E-mail berthold.hocher{at}rz.hu-berlin.de
Abstract—The aim of the present study was to analyze whether the cardiac endothelin system contributes to cardiac remodeling in rats with 2-kidney, 1 clip (2K1C) renovascular hypertension. The endothelin system seems to be a promising candidate for cardiac remodeling because endothelin (ET)-1 promotes growth of cardiomyocytes in vitro and induces cardiac collagen synthesis. The activity of the cardiac endothelin system was analyzed by measuring cardiac tissue big ET-1 and ET-1 concentrations as well as by estimating the cardiac expression of the ETA and ETB receptors 10 days, 4 weeks, and 12 weeks after the renal artery was clipped. The effects of long-term treatment with ETA, ETB, and combined ETA/ETB receptor antagonists on cardiac hypertrophy, media/lumen ratio of intracardiac arteries, and left ventricular fibrosis were also analyzed. This study demonstrated that the overall left ventricular cardiac endothelin system has a similar activity in the early, middle, and late stages of 2K1C renovascular hypertension compared with sham-operated controls. Fibrosis of the left ventricle and hypertrophy of intracardiac arteries, however, were markedly altered after long-term treatment with endothelin receptor antagonists in a blood pressure–independent manner. These 2 effects are mediated by different subtypes of endothelin receptors. ETA receptor blockade completely normalized the hypertrophy of intracardiac arteries (P<0.01 compared with 2K1C without treatment) in renovascular hypertension, whereas the ETB antagonist reduced cardiac fibrosis of the left ventricle (P<0.001 compared with 2K1C without treatment) to baseline values. This study demonstrates that the cardiac endothelin system plays an important role in the development of cardiac fibrosis as well as in hypertrophy of intracardiac arteries in 2K1C renovascular hypertensive rats.
Key Words: hypertension, renovascular • endothelins • remodeling
This article has been cited by other articles:
 |
|
 |
|
  T. Quaschning, F. Voss, K. Relle, P. Kalk, N. Vignon-Zellweger, T. Pfab, C. Bauer, F. Theilig, S. Bachmann, A. Kraemer-Guth, et al. Lack of Endothelial Nitric Oxide Synthase Promotes Endothelin-Induced Hypertension: Lessons from Endothelin-1 Transgenic/Endothelial Nitric Oxide Synthase Knockout Mice J. Am. Soc. Nephrol., March 1, 2007; 18(3): 730 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Cooper and T. P. Murphy The Case for Renal Artery Stenting for Treatment of Renal Artery Stenosis Circulation, January 16, 2007; 115(2): 263 - 270. [Full Text] [PDF]
|
|
|
|
 |
|
 T.-M. Lee, M.-S. Lin, C.-H. Tsai, and N.-C. Chang Effect of pravastatin on left ventricular mass in the two-kidney, one-clip hypertensive rats Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2705 - H2713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Dworkin Controversial Treatment of Atherosclerotic Renal Vascular Disease: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions Trial Hypertension, September 1, 2006; 48(3): 350 - 356. [Full Text] [PDF]
|
|
|
|
|
|
T. Pfab, C. Thone-Reineke, F. Theilig, I. Lange, H. Witt, C. Maser-Gluth, M. Bader, J.-P. Stasch, P. Ruiz, S. Bachmann, et al. Diabetic Endothelin B Receptor-Deficient Rats Develop Severe Hypertension and Progressive Renal Failure J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1082 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Sutherland, M. I. Nataatmadja, P. J. Walker, L. Cuttle, R. B. Garlick, and M. J. West Vascular Remodeling in the Internal Mammary Artery Graft and Association With In Situ Endothelin-1 and Receptor Expression Circulation, March 7, 2006; 113(9): 1180 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Meiners, B. Hocher, A. Weller, M. Laule, V. Stangl, C. Guenther, M. Godes, A. Mrozikiewicz, G. Baumann, and K. Stangl Downregulation of Matrix Metalloproteinases and Collagens and Suppression of Cardiac Fibrosis by Inhibition of the Proteasome Hypertension, October 1, 2004; 44(4): 471 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Yang, R. Gros, M. G. Kabir, A. Sadi, A. I. Gotlieb, M. Husain, and D. J. Stewart Conditional Cardiac Overexpression of Endothelin-1 Induces Inflammation and Dilated Cardiomyopathy in Mice Circulation, January 20, 2004; 109(2): 255 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Quaschning, S. Kocak, C. Bauer, H.-H. Neumayer, J. Galle, and B. Hocher Increase in nitric oxide bioavailability improves endothelial function in endothelin-1 transgenic mice Nephrol. Dial. Transplant., March 1, 2003; 18(3): 479 - 483. [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]
|
|
|
|
 |
|
 N. H.S. Kim and L. J. Rubin Endothelin in Health and Disease: Endothelin Receptor Antagonists in the Management of Pulmonary Artery Hypertension Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 9 - 19. [Abstract] [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]
|
|
|
|
|
|
A. W Barolet, S. Babaei, R. Robinson, P. Picard, W. Tsui, N. Nili, F. Mohamed, O. Ornatsky, J. D Sparkes, D. J Stewart, et al. Administration of exogenous endothelin-1 following vascular balloon injury: early and late effects on intimal hyperplasia Cardiovasc Res, December 1, 2001; 52(3): 468 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Riggleman, J. Harvey, and C. Baylis Endothelin Mediates Some of the Renal Actions of Acutely Administered Angiotensin II Hypertension, July 1, 2001; 38(1): 105 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Boemke, B. Hocher, N. Schleyer, M. O. Krebs, and G. Kaczmarczyk Hemodynamic, renal, and endocrine responses to acute ETA blockade at different ANG II plasma levels Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2001; 280(5): R1322 - R1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.-E. Rhaleb, H. Peng, P. Harding, M. Tayeh, M. C. LaPointe, and O. A. Carretero Effect of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline on DNA and Collagen Synthesis in Rat Cardiac Fibroblasts Hypertension, March 1, 2001; 37(3): 827 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Bianciotti and A. J. de Bold Modulation of cardiac natriuretic peptide gene expression following endothelin type A receptor blockade in renovascular hypertension Cardiovasc Res, March 1, 2001; 49(4): 808 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Torre-Amione, J. B. Young, J.-B. Durand, B. Bozkurt, D. L. Mann, I. Kobrin, and C. M. Pratt Hemodynamic Effects of Tezosentan, an Intravenous Dual Endothelin Receptor Antagonist, in Patients With Class III to IV Congestive Heart Failure Circulation, February 20, 2001; 103(7): 973 - 980. [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]
|
|
|
|
 |
|
 B. Hocher, A. Schwarz, K. A. Fagan, C. Thöne-Reineke, K. El-Hag, H. Kusserow, S. Elitok, C. Bauer, H.-H. Neumayer, D. M. Rodman, et al. Pulmonary Fibrosis and Chronic Lung Inflammation in ET-1 Transgenic Mice Am. J. Respir. Cell Mol. Biol., July 1, 2000; 23(1): 19 - 26. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. P. Rossi, A. Sacchetto, D. Rizzoni, S. Bova, E. Porteri, G. Mazzocchi, A. S. Belloni, M. Bahcelioglu, G. G. Nussdorfer, and A. C. Pessina Blockade of Angiotensin II Type 1 Receptor and Not of Endothelin Receptor Prevents Hypertension and Cardiovascular Disease in Transgenic (mREN2)27 Rats via Adrenocortical Steroid-Independent Mechanisms Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 949 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bohlender, S. Gerbaulet, J. Kramer, M. Gross, M. Kirchengast, and R. Dietz Synergistic Effects of AT1 and ETA Receptor Blockade in a Transgenic, Angiotensin II-Dependent, Rat Model Hypertension, April 1, 2000; 35(4): 992 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. MORGERA, S. KUCHINKE, K. BUDDE, A. LUN, B. HOCHER, and H.-H. NEUMAYER Volume Stress-Induced Peritoneal Endothelin-1 Release in Continuous Ambulatory Peritoneal Dialysis J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2585 - 2590. [Abstract] [Full Text]
|
|
|
|
|
|
G. P. Rossi, M. Cesari, A. C. Pessina, B. Hocher, and I. George Endothelins and Cardiac Fibrosis • Response Hypertension, November 1, 1999; e1(5): . [Full Text]
|
|
|
|
|
|
G. P. Rossi and A. C Pessina Endothelin-1 in angiotensin II-dependent hypertension: Answer to the Letter to the Editor Cardiovasc Res, November 1, 1999; 44(2): 450 - 451. [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Role of Endothelin-1 in Hypertension Hypertension, October 1, 1999; 34(4): 876 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tripiciano, C. Peluso, A. R. Morena, F. Palombi, M. Stefanini, E. Ziparo, M. Yanagisawa, and A. Filippini Cyclic Expression of Endothelin-converting Enzyme-1 Mediates the Functional Regulation of Seminiferous Tubule Contraction J. Cell Biol., May 31, 1999; 145(5): 1027 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Moser, J. Faulhaber, R. J. Wiesner, and H. Ehmke Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1389 - R1394. [Abstract] [Full Text] [PDF]
|
|