Skip to main content
SpringerLink
Log in

Adaptive and genetic alterations of the renin angiotensin system in cardiac hypertrophy and failure

  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

The risk to suffer from cardiovascular events may be modulated, in part, by neurohormonal systems. Neurohormones such as angiotensin II or aldosterone may be activated secondary to congestive heart failure or in the course of an acute myocardial infarction. These systems, if activated, will subject the failing heart to increased hemodynamic load and, thus, further compromise cardiac function. In addition, structural changes of the heart and vessels occurring with pressure or volume overload may be amplified by the growth promoting effects of these agents. Taken together, the interaction of underlying cardiovascular disease and activated neurohormones may often determine clinical symptoms and prognosis.

More recently, growing evidence suggests that the basal, genetically determined, activity of the renin angiotensin aldosterone system may relate to the development of cardiovascular disease as well. In particular, variants of the angiotensinogen and angiotensin converting enzyme genes have been associated with essential hypertension, myocardial infarction, or left ventricular hypertrophy. In this regard, the data suggest that the renin angiotensin aldosterone system may be one of the primary causes, rather than only a secondary co-factor, in the pathogenesis of these most important cardiovascular disorders.

In light of the various options of pharmacological intervention, it seems important that ongoing clinical and molecular-genetic research will further define the role of the renin angiotensin system in clinical conditions or genetic risk profiles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Badenhop RF, Wang XL, Wilcken DEL (1995) Angiotensin-converting enzyme genotype in children and coronary events in their grandparents. Circulation 91: 1655–1658

    Google Scholar 

  2. Baker KM, Cherin MI, Wixson SK, Aceto JF (1990) Renin angiotensin system involvement in pressure overload hypertrophy in rats. Am J Physiol 259: H324–332

    Google Scholar 

  3. Bruckschlegel G, Holmer SR, Jandeleit K, Grimm D, Muders F, Kromer EP, Riegger AJG, Schunkert H (1995) Blockade of the renin-angiotensin system in cardiac pressure overload hypertrophy in rats. Hypertension 25: 250–259

    Google Scholar 

  4. Cambien F, Costerousse O, Tiret L, Poirier O, Lecerf L, Gonzales MF, Evans A, Arveiler D, Cambou JP, Luc G, Rakotovao R, Ducimetiere P, Soubrier F, Alhenc-Gelas F (1994) Plasma level and gene polymorphism of angiotensin converting enzyme in relation to myocardial infarction. Circulation 90: 669–676

    Google Scholar 

  5. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouel P, Alhanc-Gelas F, Soubrier F (1992) Deletion polymorphism in the gene for angiotensin converting enzyme is a potent risk factor for myocardial infarction. Nature 359: 641–644

    Google Scholar 

  6. Castellano M, Muiesan ML, Rizzoni D, Beschi M, Pasini G, Cinelli A, Salvetti M, Porteri E, Bettoni G, Kreutz R, Lindpaintner K, Rosei EA (1995) Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general polpulation. The Vobarno study. Circulation 91: 2721–2724

    Google Scholar 

  7. Chandrasekharan UM, Sanker S, Glynias MJ, Karnik SS, Husain A (1996) Angiotensin II-forming activity in a reconstructed ancestral chymase. Science 271: 502–505

    Google Scholar 

  8. Crozier JG, Richards AM, Ikram H, Nicholls MG (1993) The renin-angiotensin system, ACE inhibitors, and cardiac structure. In: Robertson JIS, Nicholls MG (eds) The Renin-Angiotensin System, Vol 2. therapeutics. Gower Medical Publishing, London, New York, pp 94.1–94.10

    Google Scholar 

  9. Danser AHJ, Schalekamp MADH, Bax WA, Maassen van den Brink A, Saxena PR, Riegger GAJ, Schunkert H (1995) Angiotensin converting enzyme in the human heart: Effects of the deletion/insertion polymorphism. Circulation 92: 1388–1389

    Google Scholar 

  10. Doria A, Warram JH, Krolewski AS (1994) Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I-converting enzyme gene. Diabetes 43: 690–695

    Google Scholar 

  11. Drexler H, Lindpaintner K, Lu W, Schieffer B, Ganten D (1989) Transient increse in the expression of cardiac angiotensinogen in rat model of myocardial infarction and failure. ciculation 80 (Suppl II): II459

    Google Scholar 

  12. Dzau VJ, Safar MI (1988) Large conduit arteries in hypertension: role of the vascular renin-angiotensin system. Circulation 77: 947–954

    Google Scholar 

  13. Foult JM, Tavolaro O, Antony I, Nitenberg A (1988) Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: assessment by a bilateral intracoronary infusion technique. Circulation 77: 337–344

    Google Scholar 

  14. Friedrich SP, Lorell BH, Douglas PS, Gordon S, Grossman W, Benedict C, Hess OM, Krayenbuehl HP, Eberli F, Rousseau M, Pouleur H (1994) Intracardiac ACE inhibition improves diastolic distensibility in patients with left ventricular hypertrophy due to aortic stenosis. Circulation 90: 2761–2771

    Google Scholar 

  15. Gay RG (1990) Captopril reduces left ventricular enlargement induced by chronic volume overload. Am J Physiol 259: H796–803

    Google Scholar 

  16. Grossman w, Jones D, McLaurin LP (1975) Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 56: 56–64

    Google Scholar 

  17. Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ (1991) Tissue-specific activation of cardiac converting enzyme in experimental heart failure. Circ Res 69: 475–482

    Google Scholar 

  18. Husain A (1993) The chymase-angiotensin system in humans. J Hypertens 11: 1155–1159

    Google Scholar 

  19. Iwai N, Ohmichi N, Nakamura Y, Kinoshita M (1994) DD genotape of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation 90: 2622–2628

    Google Scholar 

  20. Johnston CI, Mooser V, Sun Y, Fabris B (1991) Changes in cardiac angiotensin converting enzyme after myocardial infarction and hypertrophy in rats. Clin Exp Pharm Phys 18: 107–110

    Google Scholar 

  21. Kromer EP, Riegger AJG (1988) Effects of long-term angiotensin converting enzyme inhibition on myocardial hypertrophy in experimental aortic stenosis in the rat. Am J Cardiol 62: 161–163

    Google Scholar 

  22. Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen CJ, Castelli WP (1988) Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors: the Framingham heart study. Ann Intern Med 108: 7–13

    Google Scholar 

  23. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WB (1990) Prognostic implications of echocardiographically determined LV mass in the Framingham Heart Study. N Engl J Med 322: 1561–1566

    Google Scholar 

  24. Levy D, Lindpaintner K, Larson MG, Ramachandran VS, Myers RH, Pfeffer MA, Ordovas JM, Schaefer EJ, Wilson PWF (1995) Left ventricular hypertrophy and the deletion-insertion polymorphism of the angiotensin-converting enzyme gene. J Am Coll Cardiol 25: 136A

    Google Scholar 

  25. Li C, Prakash O, Re RN (1989) Altered regulation of angiotensin gene expression in the left ventricles of the hypertensive rats. Circulation 80 (Suppl II): II-616

    Google Scholar 

  26. Lindpaintner K, Jin M, Wilhelm MJ, Susuki F, Linz W, Soelkens BA, Ganten D (1988) Intracardiac generation of angiotensin and its physiologic role. Circulation (Suppl I): I-18–24

    Google Scholar 

  27. Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH (1995) A prospective evaluation of an angiotensin converting enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 332: 706–711

    Google Scholar 

  28. Linz W, Schölkens BA, Ganten D (1989) Converting enzyme inhibition prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens 11: 1325–1350

    Google Scholar 

  29. Ludwig E, Corneli PS, Anderson JL, Marshall HW, Lalouel JM, Ward RH (1995) Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis. Circulation 91: 2120–2124

    Google Scholar 

  30. Marre M, Bernadet P, Gallois Y, Savagner F, Guyene TT, Hallab M, Cambien F, Passa P, Alhenc-Gelas F (1994) Relationships between angiotensin I-converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 43: 384–388

    Google Scholar 

  31. Mattu RK, Needham EWA, Galton DJ, Frangos E, Clark AJL, Caulfield M (1995) A DNA variant at the angiotensin-converting enzyme gene locus associates with coronary heart disease in the Caephilly Heart Study. Circulation 91: 270–274

    Google Scholar 

  32. Nagano M, Nakamura M, Tabuchi Y, Raguki H, Higashimori K, Katahira K, Tsunetoshi T, Otsuka A, Higaki J, Mikami H, Ogihara T (1990) Role of cardiac Angiotensin II in left ventricular hypertrophy of spontaneously hypertensive rats. Ciculation 82 (Suppl II): II-616

    Google Scholar 

  33. Nakai K, Itoh C, Miura Y, Hotta K, Musha T, Itoh T, Miyakawa T, Iwasaki R, Hiramori K (1994) Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation 90: 2199–2202

    Google Scholar 

  34. Ohoshi M, Raguki H, Ogihara T (1994) Association between a deletion polymorphism of the angiotensin-converting enzyme gene and left ventricular hypertrophy. N Engl J Med 331: 1097

    Google Scholar 

  35. Pfeffer JM, Pfeffer MA, Braunwald E (1985) Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res 57: 84–95

    Google Scholar 

  36. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E (1982) Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA 79: 3310–3315

    Google Scholar 

  37. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphismin of the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86: 1343–1346

    Google Scholar 

  38. Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P (1994) Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 91: 3662–3665

    Google Scholar 

  39. Sadoshima J, Izumo S (1993) Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts: critical role of the AT1 receptor subtype. Circ Res 73: 413–423

    Google Scholar 

  40. Sadoshima J, Xu J, Slayter HS, Izumo S (1993) Autocrine release of angiotensin II mediates strech induced hypertrophy of cardiac myocytes in vitro. Cell 75: 977–984

    Google Scholar 

  41. Schunkert H, Dzau VJ, Tang SS, Hirsh AT, Apstein C, Lorell B (1990) Increased rat cardiac angiotensin converting enzyme activity and mRNA levels in pressure overload left ventricular hypertrophy: effects on coronary resistance, contractility and relaxation. J Clin Invest 86: 1913–1920

    Google Scholar 

  42. Schunkert H, Hense H-W, Holmer SR, Stender M, Perz S, Keil U, Lorell BH, Riegger GAJ (1994) Association between a deletion polymorphism pf the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 330: 1634–1638

    Google Scholar 

  43. Schunkert H, Ingelfinger JR, Hirsch AT, SS Tang, S Litwin, Talsness C, Dzau VJ (1992) Evidence for tissue specific activation of renal angiotensinogen mRNA expression in chronic stable heart failure. J Clin Invest 90: 1523–1529

    Google Scholar 

  44. Schunkert H, Sadoshima J, Cornelius T, Kagaya Y, Weinberg EO, Izumo S, Riegger G, Lorell BH (1995) Angiotensin II-induced growth responses in isolated adult rat hearts. Evidence for load-independent induction of cardiac protein synthesis by angiotensin II. Circ Res 76: 489–497

    Google Scholar 

  45. Schunkert H, Tang SS, Litwin SE, Diamant D, Riegger G, Dzau VJ, Ingelfinger JR (1993) Regulation of intrarenal and circulating renin angiotensin systems in severe heart failure in the rat. Cardiovasc Res 27: 731–735

    Google Scholar 

  46. Studer R, Reinecke H, Müller B, Holtz J, Drexler H (1994) Increased angiotensin-I converting enzyme gene expression in the failing human heart: quantification by competitive RNA polymerase chain reaction. J Clin Invest 94: 301–310

    Google Scholar 

  47. Studer R, Sütsch G, Müller B, Öschlin E, Hess OM, Drexler H (1994) Role of pressure overload and wall stress for cardiac gene expression of angiotensin I converting enzyme in humans. Circulation 90 Suppl I: I-451

    Google Scholar 

  48. Tiret L, Rigat B, Visvikis S Breda C, Corvol P, Cambien F, Soubrier F (1992) Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) controls plasma ACE. Am J Hum Genet 51: 197–205

    Google Scholar 

  49. Urata H, Kinoshita A, Misono MS, Bumpus FM, Husain A (1990) Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 265: 22348–22357

    Google Scholar 

  50. Urata H, Boehm KD, Philip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A (1993) Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest 91: 1261–1281

    Google Scholar 

  51. Verhaaren HA, Schieken RM, Mosteller M, Hewitt JK, Eaves LJ, Nance WE (1991) Bivariate genetic analysis of left ventricular mass and weight in pubertal twins (the Medical College of Virginia twin study). Am J Cardiol 68: 661–668

    Google Scholar 

  52. Weinberg EO, Schoen FJ, George D, Douglas PS, Litwin SE, Kagaya Y, Schunkert H, Benedict CR, Lorell BH (1994) Angiotensin converting enzyme inhibition prolonges survival and modifies the transition to herat failure in rats with pressure overload hypertrophy due to ascending aortic stenosis. Circulation 90: 1410–1422

    Google Scholar 

  53. Yamada H, Fabris B, Allen AM, Jackson B, Johnston C, Mendelsohn FAO (1991) Localization of angiotensin converting enzyme in the rat heart. Circ Res 68: 141–149

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Franz-Josef-Strauß-Allee 11, D-93042, Regensburg, Germany

    S. R. Holmer & H. Schunkert

Authors
  1. S. R. Holmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Schunkert
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holmer, S.R., Schunkert, H. Adaptive and genetic alterations of the renin angiotensin system in cardiac hypertrophy and failure. Basic Res Cardiol 91 (Suppl 1), 65–71 (1996). https://doi.org/10.1007/BF00795365

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00795365

Key words

Search

Navigation