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The role of the renin-angiotensin-aldosterone system in heart failure
Thomas Unger
Centre for Cardiovascular Research (CCR)/Institute of Pharmacology and Toxicology, Charité University Medicine Berlin, Berlin, Germany, thomas.unger{at}charite.de
Jun Li
Centre for Cardiovascular Research (CCR)/Institute of Pharmacology and Toxicology, Charité University Medicine Berlin, Berlin, Germany
Activity of the renin-angiotensin-aldosterone system (RAAS) is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation.
Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third-generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease.)
Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II) (in addition to angiotensin-converting enzyme [ACE]), has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo.
Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation.
Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.
Key Words: heart failure • RAAS • renin • chymase • bradykinin • angiotensin II
References
- Tigerstedt R., Bergman PG Niere und Kreislauf. Skand Arc Physiol 1898;8:223-71.
- Brunner HR, Laragh JH, Baer L. et al. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972;286:441-9.[Web of Science][Medline]
[Order article via Infotrieve]
- Alderman MH, Madhavan S., Ooi WL, Cohen H., Sealey JE, Laragh JH Association of the renin-sodium profile with the risk of myocardial infarction in patients with essential hypertension. N Engl J Med 1991;324:1098-104.[Abstract]
- Danser AH, van Kesteren CA, Bax WA et al. Prorenin, renin, angiotensinogen and angiotensin converting enzyme in normal and failing human hearts. Evidence from renin binding. Circulation 1997;96:220-6.[Abstract/Free Full Text]
- Barlucchi L., Leri A., Dostal DE et al. Canine ventricular myocytes possess a renin-angiotensin system that is upregulated with heart failure. Circ Res 2001;88:298-304.[Abstract/Free Full Text]
- Nguyen G., Delarue F., Burckle C. et al. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest 2002;109:1417-27.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Stanton A. Potential of renin inhibition in cardiovascular disease. JRAAS 2003;4:6-10.[Medline]
[Order article via Infotrieve]
- Stanton A., Barton J., Jensen C., Bobilliner A., Mann J., O'Brien E. Dose response antihypertensive efficacy of aliskiren, an orally active renin inhibitor.AmJHypertens 2002;15:56A.
- Fisher NDL, Allan D., Kifor A. et al. Responses to converting enzyme and renin inhibition: role of angiotensin II in humans. Hypertension 1994;23:44-51.[Abstract/Free Full Text]
- Kokkonen JO, Lindstedt KA, Kovanen PT Role for chymase in heart failure. Circulation 2003;107:2522.[Free Full Text]
- PatellaV, Marino I.,Arbustini E. et al. Stem cell factor in mast cells and increased mast cell density in idiopathic and ischaemic cardiomyopathy. Circulation 1998;97:971-8.[Abstract/Free Full Text]
- SukenagaY, Kamoshita K.,Takai S., Migazaki M. Development of the chymase inhibitor as an anti-tissue remodelling drug in myocardial infarction and some other possibilities. Jpn J Pharmacol 2002;90:218-22.[CrossRef][Medline]
[Order article via Infotrieve]
- Matsumoto T., Wada A., Tsutamoto T., Ohnishi M., Isono T., Kinoshita M. Chymase inhibition prevents cardiac fibrosis and improves diastolic dysfunction in the progression of heart failure. Circulation 2003;107:2555-8.[Abstract/Free Full Text]
- Petrie MI, Padmanabhan N., McDonald JE et al.Angiotensin converting enzyme (ACE) and non-ACE dependent angiotensin II generation in resistance arteries from patients with heart failure and coronary heart disease. J Am Coll Cardiol 2001;37: 57-61.
- Blais C. Jr, Drapeau G., Raymond P. et al. Contribution of angiotensin converting enzyme to the cardiac metabolism of bradykinin; An interspecies study. Am J Physiol 1997;273: H2263-71.[Web of Science][Medline]
[Order article via Infotrieve]
- Gainer JV, Morrow JD, Loveland A. et al. Effect of bradykinin-receptor blockade on the response to ACE inhibitors in normotensive and hypertensive patients. N Engl J Med 1998;339: 1285-92.[Abstract/Free Full Text]
- Bao G., Gohlke P., Qadri F. et al. Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril. Hypertension 1992;20:74-9.[Abstract/Free Full Text]
- Danckwardt L., Shimizu I., Bonner G. et al. Converting enzyme inhibition in kinin-deficient brown Norway rats. Hypertension 1990;16:429-35.[Abstract/Free Full Text]
- Witherow FN, Helmy A., Webb DJ, Fox KAA, Newby JDE. Bradykinin contributes to the vasodilatory effects of chronic ACE inhibition in patients with heart failure. Circulation 2001;104:2177-81.[Abstract/Free Full Text]
- Nikolaidis LA, Doverspike A., Huerbin R., Hentosz T., Shannon RP ACE inhibitors improve coronary flow reserve in dilated cardiomyopathy by a bradykinin-mediated, nitric oxide-dependent mechanism. Circulation 2002;105:2785-90.[Abstract/Free Full Text]
- Gohlke P., Kuwer I., Schnell A. et al. Blockade of bradykinin B2 receptors prevents the increase in capillary density induced by chronic angiotensin-converting enzyme inhibitor treatment in stroke-prone spontaneously hypertensive rats. Hypertension 1997;29:478-82.[Abstract/Free Full Text]
- Unger T., Mattfeldt T., Lamberty V. et al. Effect of early onset angiotensin converting enzyme inhibition on myocardial capillaries. Hypertension 1992;20:478-82.[Abstract/Free Full Text]
- Fujii M., Wada A., Tsutamoto T., Ohnishi M., Isono T., Kinoshita M. Bradykinin improves left ventricular diastolic function under long-term ACE inhibition in heart failure. Hypertension 2002;39:952.[Abstract/Free Full Text]
- Zisman LS,Abraham WT, Meixell GE et al.Angiotensin II formation in the intact human heart. Predominance of the angiotensin converting enzyme pathway. J Clin Invest 1995;96: 1490-8.[Web of Science][Medline]
[Order article via Infotrieve]
- Dell'Italia LJ, Sabri A. Activation of the renin-angiotensin system in hypertrophy and heart failure. In: Heart failure, Ed Mann DL. Philadelphia PA: Saunders, 2004.
- Serneri GG, Boddi M., Cecioni I. et al. Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular function. Circ Res 2001;88:861-3.[Free Full Text]
- Leri A., Claudio PP, Li Q. et al. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases Bal-2-to-Bax protein ratio in the cell.JClinInvest 1998;101:1326-42.[Web of Science][Medline]
[Order article via Infotrieve]
- Busche S., Gallinat S., Bohle RM et al. Expression of angiotensin AT(1) and AT(2) receptors in adult rat cardiomyocytes after myocardial infarction. A single-cell reverse transcriptase-polymerase chain reaction study. Am J Pathol 2000;157:605-11.[Abstract/Free Full Text]
- TsutsumiY, Matsubara H., Ohkubo N. et al.Angiotensin type 2 receptor is upregulated in human heart with interstitial fibrosis, and cardiac fibroblasts are the major cell type for its expression. Circ Res 1998;83:1035-46.[Abstract/Free Full Text]
- Zhu YZ, Zhu YC, Li J. et al. Effects of losartan on haemodynamic parameters and angiotensin II receptor mRNA levels in rat heart after myocardial infarction. JRAAS 2000;1:257-62.[Medline]
[Order article via Infotrieve]
- Nio Y., Matsubara H., Murasawa S. et al. Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest 1995;95:46-54.[Web of Science][Medline]
[Order article via Infotrieve]
- Sadoshima J., Izumo S. Molecular characterisation of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Circ Res 1993;73:413-23.[Abstract/Free Full Text]
- Stauss HM, Zhu YC, Redlich T. et al. Angiotensin-converting enzyme inhibition in infarct-induced heart failure in rats: bradykinin versus angiotensin II. J Cardiovasc Risk 1994;1:25562.
- Xia QG, Chung O., Spitznagel H. et al. Significance of timing of angiotensin AT1 receptor blockade in rats with myocardial infarction-induced heart failure. Cardiovasc Res 2001;49:110-17.[Abstract/Free Full Text]
- Mankad S., d'Amato TA, Reichek N. et al. Combined angiotensin II antagonism and ACE inhibition further attenuates post-infarction left ventricular remodelling. Circulation 2001;103:2845-50.[Abstract/Free Full Text]
- Kawano H., Do YS, Kawano W. et al. Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts. Circulation 2000;101:30-7.
- Stoll M., Steckelings UM, Paul M. et al. The angiotensin AT2 receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995;95:651-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Meffert S., Stoll M., Steckelings UM et al.The angiotensin AT2 receptor inhibits proliferation and promotes differentiation in PC12W cells. Molecular Cellular Endocrinol 1996;122:59-67.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Lucius R., Gallinat S., Rosenstiel P. et al.The angiotensin II type 2 (AT2) receptor promotes axonal regeneration in the optic nerve of adult rats.JExp Med 1998;188:661-70.[Abstract/Free Full Text]
- Reinecke K., Lucius R., Reinecke A. et al. Angiotensin II increases the rate of functional recovery in the rat sciatic nerve in vivo: role of the AT2 receptor. FASEB J 2003;17:2094-6.[Abstract/Free Full Text]
- Bloor CM, Nimmo L., McKirnan MD et al. Increased gene expression of plasminogen activators and inhibitors in left ventricular hypertrophy.Mol Cell Biochem 1997;176:265-71.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Chua CC, Handy RC, Chua BH Angiotensin II induces TIMP-1 production in rat heart endothelial cells. Biochym Biophys Acta 1996;1311:175-80.[Medline]
[Order article via Infotrieve]
- Eguchu S., Numaguchi K., Iwasaki H. et al. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 1998;273:8890-6.[Abstract/Free Full Text]
- Van Aelst L., D'Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev 1997;11:2295-332.[Free Full Text]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 1 suppl,
S7-S10 (2004)
DOI: 10.3317/jraas.2004.024
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