JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
 QUICK SEARCH:   [advanced]


     


J Am Coll Cardiol, 2003; 41:666-673, doi:10.1016/S0735-1097(02)02860-7
© 2003 by the American College of Cardiology Foundation
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seccia, T. M.
Right arrow Articles by Rossi, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seccia, T. M.
Right arrow Articles by Rossi, G. P.

CLINICAL STUDY: HYPERTENSION

Cardiac fibrosis occurs early and involves endothelin and AT-1 receptors in hypertension due to endogenous angiotensin II

Teresa M. Seccia, MD*, Anna S. Belloni, BSc{dagger}, Reinhold Kreutz, MD{ddagger}, Martin Paul, MD{ddagger}, Gastone G. Nussdorfer, MD{dagger}, Achille C. Pessina, MD, PhD§ and Gian Paolo Rossi, MD, FACC§,*

* Department of Clinical Methodology and Clinical-Surgical Technologies, University of Bari, Bari, Italy
{dagger} Department of Human Anatomy and Physiology (Section of Anatomy), University of Padova, Padova, Italy
{ddagger} Institute of Clinical Pharmacology and Toxicology, Freie University of Berlin, Berlin, Germany
§ Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Padova, Italy

Manuscript received June 19, 2002; accepted October 17, 2002.

* Reprint requests and correspondence: Dr. Gian Paolo Rossi, Dept. of Clinical and Experimental Medicine, Clinica Medica 4, University Hospital, via Giustiniani, 2, 35126 Padova, Italy.
gianpaolo.rossi{at}unipd.it

OBJECTIVES: We investigated if endothelin (ET)-1 and the renin-angiotensin-aldosterone system play a role in cardiac fibrosis.

BACKGROUND: Angiotensin II (Ang II) can induce cardiac fibrosis, but the underlying mechanisms are incompletely understood.

METHODS: Four-week-old transgenic (mRen2)27 rat (TGRen2) received for four weeks a placebo, the mixed ETA/ETB endothelin receptor antagonist bosentan, the angiotensin II type I receptor (AT-1) antagonist irbesartan, the ETA endothelin receptor antagonist BMS-182874, and a combined treatment with irbesartan plus BMS-182874. We measured collagen density on Sirius red–stained serial sections of the left ventricle (LV) with a photomicroscope equipped with specific software and assessed the gene expression of procollagen {alpha}1(I), atrial natriuretic peptide (ANP), transforming growth factor-beta 1 (TGFß1), endothelin converting enzyme, and ETB receptor.

RESULTS: In the placebo group, hypertension was associated with LV hypertrophy and cardiac fibrosis (LV weight: 4.0 ± 0.3 mg/g body weight; collagen density: 2.21 ± 0.16%), which were all prevented with irbesartan (2.3 ± 0.1, 1.30 ± 0.13, p < 0.001), but not with BMS-182874 (4.0 ± 0.2, 2.41 ± 0.22). Bosentan also prevented fibrosis (1.39 ± 0.18) but not hypertension and LV hypertrophy (3.38 ± 0.27). Combined irbesartan and BMS-182874 treatment prevented LV hypertrophy (2.9 ± 0.1) but not fibrosis (2.52 ± 0.16). Collagen density correlated (r = 0.414, p < 0.05) with plasma aldosterone levels. In TGRen2 with LV hypertrophy, the gene expression of ANP and ETB but not that of TGFß1 and procollagen {alpha}1(I) was increased.

CONCLUSIONS: In Ang II–dependent hypertension, cardiac fibrosis was associated with LV hypertrophy and was hindered by both mixed ETA/ETB blockade and AT-1 blockade. Only the latter treatment prevented both hypertension and LV hypertrophy. Thus, there is a dissociation between the mechanisms of cardiac fibrosis and hypertension, which do and do not entail ET-1, respectively.

Abbreviations and Acronyms
  Ang II
  angiotensin II
  ANP
  atrial natriuretic peptide
  AT-1
  angiotensin II type I receptor
  BP
  blood pressure
  BW
  body weight
  DOCA
  deoxycorticosterone acetate
  ET-1
  endothelin-1
  LV
  left ventricle
  RAAS
  renin-angiotensin-aldosterone system
  TGFß1
  transforming growth factor-beta 1
  TGRen2
  transgenic (mRen2)27 rat
  2K1C
  2 kidney 1 clip model




This article has been cited by other articles:


Home page
Eur Heart JHome page
C. F. Opitz, R. Ewert, W. Kirch, and D. Pittrow
Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?
Eur. Heart J., August 2, 2008; 29(16): 1936 - 1948.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
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]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
V. G. DeMarco, J. Habibi, A. T. Whaley-Connell, R. I. Schneider, R. L. Heller, J. P. Bosanquet, M. R. Hayden, K. Delcour, S. A. Cooper, B. T. Andresen, et al.
Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat
Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2659 - H2668.
[Abstract] [Full Text] [PDF]


Home page
Eur J EchocardiogrHome page
H. Pavlopoulos, J. Grapsa, E. Stefanadi, V. Kamperidis, E. Philippou, D. Dawson, and P. Nihoyannopoulos
The evolution of diastolic dysfunction in the hypertensive disease
Eur J Echocardiogr, April 29, 2008; (2008) jen145v1.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
S. Wong, F. E. Brennan, M. J. Young, P. J. Fuller, and T. J. Cole
A Direct Effect of Aldosterone on Endothelin-1 Gene Expression in Vivo
Endocrinology, April 1, 2007; 148(4): 1511 - 1517.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
P. A. Gould, M. Yii, M. D. Esler, J. M. Power, and D. M. Kaye
Atrial fibrillation impairs cardiac sympathetic response to baroreceptor unloading in congestive heart failure
Eur. Heart J., December 1, 2005; 26(23): 2562 - 2567.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
E. A. Thackaberry, Z. Jiang, C. D. Johnson, K. S. Ramos, and M. K. Walker
Toxicogenomic Profile of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in the Murine Fetal Heart: Modulation of Cell Cycle and Extracellular Matrix Genes
Toxicol. Sci., November 1, 2005; 88(1): 231 - 241.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
I. Vaneckova, H. J. Kramer, A. Backer, Z. Vernerova, M. Opocensky, and L. Cervenka
Early Endothelin-A Receptor Blockade Decreases Blood Pressure and Ameliorates End-Organ Damage in Homozygous Ren-2 Rats
Hypertension, October 1, 2005; 46(4): 969 - 974.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
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]


Home page
HypertensionHome page
D. M. Pollock
Endothelin, Angiotensin, and Oxidative Stress in Hypertension
Hypertension, April 1, 2005; 45(4): 477 - 480.
[Full Text] [PDF]


Home page
DiabetesHome page
C. Tikellis, P. J. Wookey, R. Candido, S. Andrikopoulos, M. C. Thomas, and M. E. Cooper
Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat
Diabetes, April 1, 2004; 53(4): 989 - 997.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
N. G Perez, M. C Villa-Abrille, E. A Aiello, R. A Dulce, H. E Cingolani, and M. C Camilion de Hurtado
A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release
Cardiovasc Res, December 1, 2003; 60(3): 589 - 597.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
T.-H. Cheng, P.-Y. Cheng, N.-L. Shih, I.-B. Chen, D. L. Wang, and J.-J. Chen
Involvement of reactive oxygen species in angiotensin II-induced endothelin-1 gene expression in rat cardiac fibroblasts
J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1845 - 1854.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
Q. Pu, M. F. Neves, A. Virdis, R. M. Touyz, and E. L. Schiffrin
Endothelin Antagonism on Aldosterone-Induced Oxidative Stress and Vascular Remodeling
Hypertension, July 1, 2003; 42(1): 49 - 55.
[Abstract] [Full Text] [PDF]




HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
Copyright © 2003 by the American College of Cardiology Foundation.