© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Interactions between endothelin-1 and the renin–angiotensin–aldosterone system
Department of Clinical & Experimental Medicine, University of Padova, Padova, Italy
* Corresponding author. Tel.: +39-49-821-3304 or 2301; fax: +39-49-880-2252 gprossi{at}ux1.unipd.it
The renin–angiotensin–aldosterone (RAA) system and the endothelin (ET) system entail the most potent vasopressor mechanisms identified to date. Although they were studied in depth in relation to arterial hypertension and cardiovascular diseases, limited information on their interrelationships in causing hypertension and related target organ damage exists. The identification of consensus sequences for jun in the regulatory region of the preproendothelin-1 (ppET-1) gene raised the possibility of its transcriptional regulation by angiotensin II (Ang II). This was confirmed by the finding that stimulation with Ang II of cultured vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) induced expression of the ppET-1 gene and synthesis of ET-1. Endogenously produced ET-1 was found to contribute to the hypertrophic response of cardiomyocytes to Ang II and thereby to cardiac hypertrophy. Furthermore, ET-1 exerts multifaceted effects on the RAA system, such as dose-dependent inhibition of renin synthesis, and stimulation of aldosterone secretion. The finding of abundant specific ET-1 receptors in the adrenocortical zona glomerulosa (ZG) suggested a direct secretagogue effect of ET-1. In rats, ETB receptors mediate such an effect, whilst in humans, both ETA and ETB receptor subtypes intervene in regulating the transcription of the aldosterone synthase gene. In addition, ET-1 stimulates DNA synthesis and proliferation of ZG cells via ETA receptors and, therefore, might play a role in cell turnover of the normal adrenal cortex and in the onset of adrenal tumours. Studies on the in vivo interactions between ETs and the RAA system have given conflicting results, insofar as some suggested a participation of ET-1 in the pressor and cellular effects of exogenously administered Ang II, whereas others did not in the transgenic TGR(Ren 2m)27 rats and in the two-kidney, one clip.
KEYWORDS Angiotensin; Endothelins; Hypertension; Renin–angiotensin system; Receptors
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
V. A. Rufanova, V. F. Pozdnev, E. I. Kalenikova, A. B. Postnikov, A. N. Storozhilova, V. P. Masenko, O. A. Gomazkov, O. S. Medvedev, and N. A. Medvedeva Endothelin-Converting Enzyme Inhibition in the Rat Model of Acute Heart Failure: Heart Function and Neurohormonal Activation Exp Biol Med, October 1, 2009; 234(10): 1201 - 1211. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Dhaun, I. M. MacIntyre, V. Melville, P. Lilitkarntakul, N. R. Johnston, J. Goddard, and D. J. Webb Blood Pressure-Independent Reduction in Proteinuria and Arterial Stiffness After Acute Endothelin-A Receptor Antagonism in Chronic Kidney Disease Hypertension, July 1, 2009; 54(1): 113 - 119. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Castro-Chaves, R. Fontes-Carvalho, M. Pintalhao, P. Pimentel-Nunes, and A. F. Leite-Moreira Angiotensin II-induced increase in myocardial distensibility and its modulation by the endocardial endothelium in the rabbit heart Exp Physiol, June 1, 2009; 94(6): 665 - 674. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Y. Lai, A. E. G. Persson, B. Bodin, O. Kallskog, A. Andersson, U. Pettersson, P. Hansell, and L. Jansson Endothelin-1 and pancreatic islet vasculature: studies in vivo and on isolated, vascularly perfused pancreatic islets Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1616 - E1623. [Abstract] [Full Text] [PDF] |
||||
![]() |
R Charu, T Stobdan, R B Ram, A P Khan, M A Qadar Pasha, T Norboo, and F Afrin Susceptibility to high altitude pulmonary oedema: role of ACE and ET-1 polymorphisms. Thorax, November 1, 2006; 61(11): 1011 - 1012. [Full Text] [PDF] |
||||
![]() |
M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Dhaun, J. Goddard, and DavidJ. Webb The Endothelin System and Its Antagonism in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2006; 17(4): 943 - 955. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bielinska, S. Kiiveri, H. Parviainen, S. Mannisto, M. Heikinheimo, and D. B. Wilson Gonadectomy-induced Adrenocortical Neoplasia in the Domestic Ferret (Mustela putorius furo) and Laboratory Mouse Veterinary Pathology, March 1, 2006; 43(2): 97 - 117. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-C. Juan, Y. Chien, L.-Y. Wu, W.-M. Yang, C.-L. Chang, Y.-H. Lai, P.-H. Ho, C. F. Kwok, and L.-T. Ho Angiotensin II Enhances Insulin Sensitivity in Vitro and in Vivo Endocrinology, May 1, 2005; 146(5): 2246 - 2254. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Goddard, C. Eckhart, N. R. Johnston, A. D. Cumming, A. J. Rankin, and D. J. Webb Endothelin A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Are Synergistic via an Endothelin B Receptor-Mediated and Nitric Oxide-Dependent Mechanism J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2601 - 2610. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Dupuis Increased endothelin levels in congestive heart failure: does it come from the lungs? Does it matter? Cardiovasc Res, July 1, 2004; 63(1): 5 - 7. [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] |
||||
![]() |
H.-J. Hong, P. Chan, J.-C. Liu, S.-H. Juan, M.-T. Huang, J.-G. Lin, and T.-H. Cheng Angiotensin II induces endothelin-1 gene expression via extracellular signal-regulated kinase pathway in rat aortic smooth muscle cells Cardiovasc Res, January 1, 2004; 61(1): 159 - 168. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nishiyama, H. Kobori, T. Fukui, G.-X. Zhang, L. Yao, M. Rahman, H. Hitomi, H. Kiyomoto, T. Shokoji, S. Kimura, et al. Role of Angiotensin II and Reactive Oxygen Species in Cyclosporine A-Dependent Hypertension Hypertension, October 1, 2003; 42(4): 754 - 760. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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. Yia, H. Wne, S. Bobst, M.-C. Day, and R. E. Kellems Maternal Autoantibodies From Preeclamptic Patients Active Angiotensin Receptors on Human Trophoblast Cells Reproductive Sciences, February 1, 2003; 10(2): 82 - 93. [Abstract] [PDF] |
||||
![]() |
M. Kozakova, S. Buralli, C. Palombo, G. Bernini, A. Moretti, S. Favilla, S. Taddei, and A. Salvetti Myocardial Ultrasonic Backscatter in Hypertension: Relation to Aldosterone and Endothelin Hypertension, February 1, 2003; 41(2): 230 - 236. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Vittorio, C. C. Lang, S. D. Katz, M. Packer, D. M. Mancini, and U. P. Jorde Vasopressor Response to Angiotensin II Infusion in Patients With Chronic Heart Failure Receiving {beta}-Blockers Circulation, January 21, 2003; 107(2): 290 - 293. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. P. Rossi, C. Ganzaroli, M. Cesari, A. Maresca, M. Plebani, G. G. Nussdorfer, and A. C. Pessina Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension Cardiovasc Res, January 1, 2003; 57(1): 277 - 283. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Fortuno, A. Rodriguez, J. Gomez-Ambrosi, P. Muniz, J. Salvador, J. Diez, and G. Fruhbeck Leptin Inhibits Angiotensin II-Induced Intracellular Calcium Increase and Vasoconstriction in the Rat Aorta Endocrinology, September 1, 2002; 143(9): 3555 - 3560. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. P. Rossi, M. Cavallin, A. S Belloni, G. Mazzocchi, G. G Nussdorfer, A. C Pessina, and S. Sartore Aortic smooth muscle cell phenotypic modulation and fibrillar collagen deposition in angiotensin II-dependent hypertension Cardiovasc Res, July 1, 2002; 55(1): 178 - 189. [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] |
||||
![]() |
T. DSCHIETZIG, C. RICHTER, C. BARTSCH, M. LAULE, F. P. ARMBRUSTER, G. BAUMANN, and K. STANGL The pregnancy hormone relaxin is a player in human heart failure FASEB J, October 1, 2001; 15(12): 2187 - 2195. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Ruschitzka, T. Quaschning, G. Noll, A. deGottardi, M. F. Rossier, F. Enseleit, D. Hurlimann, T. F. Luscher, and S. G. Shaw Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11{beta}-Hydroxysteroid Dehydrogenase Inhibition : Role of Nitric Oxide Circulation, June 26, 2001; 103(25): 3129 - 3135. [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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
S.M Gardiner and T Bennett Comment on "Interactions between endothelin-1 and the renin-angiotensin-aldosterone system" Cardiovasc Res, November 1, 1999; 44(2): 449 - 449. [Full Text] [PDF] |
||||
















