Summary
Myocardial hypertrophy in response to hemodynamic overload is an established risk factor for cardiovascular morbidity and mortality. Partially, this may be due to alterations in cardiac gene expression, resulting in a more fetal-like myocyte phenotype with a fragile Ca++-homeostasis. Depressed expression of the sarcoplasmic reticulum Ca++-ATPase is the hallmark of this overload phenotype, contributing to prolonged cytosolic Ca++-transients, disturbed diastolic relaxation, altered force-frequency relation, and probably, electrophysiologic instability with susceptibility to malignant arrhythmias. Since angiotensin II is a growth-promoting factor in several cellular systems, the local formation of angiotensin II within the myocardium might contribute to the trophic response and the phenotype shift of overloaded myocardium. Several observations are consistent with this hypothesis: the cardiac expression of ACE and angiotensinogen is enhanced in experimental myocardial overload and in human endstage congestive heart failure; prolonged observations of experimental cardiac overload with hypertrophy-induced putative normalisation of myocardial systolic wall stress demonstrated a renormalization of ventricular tissue ACE activity and of ventricular sarcoplasmic Ca++-ATPase expression and activity; normalizing ventricular tissue ACE activity in experimental cardiac overload by chronic nonhypotensive ACE inhibitor therapy caused a parallel partial normalization of hypertrophy and underexpression of sarcoplasmic CA++-ATPase. This partial normalization of myocyte Ca++-homeostasis in overload hypertrophy by nonhypotensive chronic ACE-inhibition is attenuated by concomitant chronic application of bradykinin-2 receptor blockade, indicating an involvement of altered bradykinin metabolism in the phenotype modulation due to chronic ACE inhibition. While these observations are consistent with a direct influence of local ACE activity on the sarcolasmic reticulum, the cell type contributing to the enhanced ACE expression in overload and the specific mechanism of this influence are unknown.
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References
Aceto JF, Baker KM (1990) [Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells. Am J Physiol 258:H806–H813
Admiraal PJJ, Derkx FHM, Danser AHJ, Pieterman H, Schalekamp MADH (1990) Metabolism and production of angiotensin I in different vascular beds in subjects with hypertension. Hypertension 15:44–55
Admiraal PJJ, Derkx FHM, Danser AHJ, Pieterman H, Schalekamp MADH (1990) Intrarenal de novo production of angiotensin I in subjects with renal artery stenosis. Hypertension 16:555–563
Anderson PG, Allars MA, Thomas GD, Bishop SP, Digerness SB (1990) Increased ischemic injury but decreased hypoxic injury in hypertrophied rat hearts. Circ Res 67:948–959
Allgeier J, Goetz RM, Studer R, Reiniçke H, Holtz J (1992) Involvement of bradykinin in the cardioreparation by chronic quinapril in rats with hypertensive left ventricular hypertrophy (Abstr). Circulation (in press)
Aronow WS, Epstein S, Koenigsberg M (1990) Usefulness of echocardiographic left ventricular hypertrophy and silent ischemia in predicting new cardiac events in elderly patients with systemic hypertension or coronary artery disease. Angiology 41:189–193
Baker KM, Aceto JF (1990) Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 259:H610–H618
Baker KM, Booz GW, Dostal DE (1992) Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol 54:227–241
Baker KM, Chemin MI, Wixson SK, Aceto JF (1990) Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. Am J Physiol 259:324–332
Baker KM, Dostal DE, Chemin MI, Wealand AL, Conrad KM (1991) Angiotensin II-mediated cardiac hypertrophy in adult rats (Abstr). J Cell Biochem 15C167
Bao G, Gohlke P, Qadri F, Unger T (1992) Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril. Hypertension 20:74–79
Bao G, Qadri F, Stauss H, Gohlke P, Unger T (1991) Hoe 140, a highly potent and long acting bradykinin antagonist in conscious rats. Eur J Pharmacol 200:179–182
Beuckelmann DJ, Erdmann E (1992) Ca2+-currents and intracellular [Ca2+]i-transients in single ventricular myocytes isolated from terminally failing human myocardium. In: Hasenfuss G, Holubarsch C, Just H, Alpert NR (eds) Cellular and molecular alterations in the failing human heart, Steinkopff Verlag Darmstadt pp. 235–243
Bing O, Brooks WW, Conrad CH, Sen S, Perreault CL, Morgan JP (1991) Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure. Circ Res 68:1390–1400
Campbell DJ (1985) The site of angiotensin production. J Hypertension 3:199–207
Campbell DJ (1987) Circulating and tissue angiotensin system. J Clin Invest 79:1–6
Campbell DJ, Kladis A (1990) Simultaneous radioimmunoassay of six angiotensin peptides in arterial and venous plasma of man. J Hypertension 8:165–172
Casale PN, Devereux RB, Milner M, Zullo G, Hershfield GA, Pickering TG, Laragh JH (1986) Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 105:173–178
Chien KR, Knowlton KU, Zhu H, Chien S (1991) Regulation of cardiac gene expression during myocardial growth and hypertrophy. Molecular studies of an adaptive physiologic response (Review), FASEB J 5:3037–3046
Cooper RS, Simmons BE, Castener A, Santhanam V, Ghali J, Mar M (1990) Left ventricular hypertrophy is associated with worse survival independent of ventricular function and number of coronary arteries severely narrowed. Am J Cardiol 65:441–445
De La Bastie D, Levitski D, Rappaport L, Mecardier JJ, Marotte F, Wisnewsky C, Brovkovich V, Schwartz K, Lompre AM (1990) Function of the sarcoplasmic reticulum and expression of its Ca2+-ATPase gene in pressure overload-induced cardiac hypertrophy in the rat. Circ Res 66:554–564
Dzau VJ (1989) Multiple pathways of angiotensin production in the blood vessel wall: evidence, possibilities and hypotheses. J Hypertension 7:933–936
Eberli FE, Apstein CS, Ngoy S, Lorell BH (1992) Exacerbation of left ventricular ischemic diastolic dysfunction by pressure-overload hypertrophy. Modification by specific inhibition of cardiac angiotensin converting enzyme. Circ Res 70:931–943
El Amrani AIK (1991) Dual effect of angiotensin II and load on intrinsic myocardial contractility. Heart Failure 7:97–103
Finckh M, Hellmann W, Ganten D, Furtwängler A, Allgeier J, Boltz M, Holtz J (1991) Enhanced cardiac angiotensinogen gene expression and angiotensin converting enzyme activity in tachypacing-induced heart failure in rats. Basic Res Cardiol 86:303–316
Fozzard HA, January CT (1988) Delayed afterdepolarizations in heart muscle: mechanisms and relevance. Pharmacol Rev 40:219–227
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
Gaasch WH, Zile MR, Hoshino PK, Weinberg EO, Rhodes DR, Apstein CS (1990) Tolerance of the hypertrophic heart to ischemia: Studies in compensated and failing dog hearts with pressure overload hypertrophy. Circulation 81:1644–1653
Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 61:70–76
Gwathmey JK, Slawsky MT, Hajjar RJ, Briggs GM, Morgan JP (1990) Role of intracellular calcium handling in force interval relationship of human ventricular myocardium. J Clin Invest 85:1599–1613
Hasenfuss G, Mulieri LA, Leavitt BJ, Allen PD, Haeberle JR, Alpert NR (1992) Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ Res 70:1225–1232
Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ (1991) Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 69:475–482
Hock FJ, Wirth K, Linz W, Gerhards HJ, Wiemer G, Henke ST, Breipohl KG, König W, Knolle J, Schölkens BA (1991) Hoe 140 a new potent and long acting bradykinin-antagonist: In vitro studies. Br J Pharmacol 102:769–773
Holmberg SRM, Williams AJ (1989) Single channels recordings from human cardiac sarcoplasmic reticulum. Circ Res 65:1445–1449
Ikenouchi H, Kohmoto O, McMillan M, Barry WH (1991) The contribution of [Ca2+]i and pHi to altered diastolic myocyte tone during partial metabolic inhibition. J Clin Invest 88:55–61
Jenne DE, Tschopp J (1991) Angiotensin II-forming heart chymase is a mast-cell specific enzyme. Biochem J 276:567–568
Katz AM (1990) Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure. N Engl J Med 322:100–110
Kléber AG (1992) The potential role of Ca2+ for electrical cell uncoupling and conduction block on myocardial tissue. In: Holtz J, Drexler H, Just H (eds) Cardiac adaptation in heart failure: risks due to myocardial phenotype changes. Steinkopff, Darmstadt (in press)
Komuro I, Kurabayashi M, Shibazaki Y, Takaku F, Yazaki Y (1989) Molecular cloning and characterization of the Ca2+ + Mg2+-dependent adenosine triphosphatase from rat cardiac sarcoplasmic reticulum. J Clin Invest 83:1102–1108
Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH (1991) Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 114:345–352
Lakatta EG (1989) Chaotic behaviour of myocardial cells: possible implications regarding the pathophysiology of heart failure. Perspect Biol Med 32:421–433
Lakatta EG, Capogrossi MC, Kort AA, Stern MD (1985) Spontaneous myocardial Ca oscillations: an overview with emphasis on ryanodine and caffeine. Fed Proc 44:2977–2983
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP (1990) Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study. N Engl J Med 322:1561–1566
Li K, Chen X (1987) Protective effects of Captopril and enalapril on myocardial ischemia and reperfusion damage of rat. J Mol Cell Cardiol 19:909–915
Limas CJ, Olivari MT, Goldenberg IF, Levine TB, Benditt DG, Simon A (1987) Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res 21:601–605
Lindpainter K, Ganten D (1991) The cardiac renin-angiotensin system. An appraisal of present experimental and clinical evidence. Circ Res 68:905–921
Lindpaintner K, Lu W, Niedermaier N, Schieffer B, Just H, Ganten D, Drexler H (1992) Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat. J Mol Cell Cardiol (in press)
Linz W, Schölkens BA, Kaiser J, Just M, Bei-Yin Q, Albus U, Petry P (1989) Cardiac arrhythmias are ameliorated by local inhibition of angiotensin formation and bradykinin degradation with the converting-enzyme inhibitor ramipril. Cardiovasc Drugs and Ther 3:873–882
Linz W, Schölkens BA, Ganten D (1989) Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens A 11:1325–1350
Lorell BH, Weinberg E, Ngoy S, Apstein CS (1986) Angiotensin II directly impairs diastolic function in pressure-overload hypertrophy (Abstr.) Circulation 82:III-12
Lorell BH, Wexler LF, Momomura S, Weinberg EO, Apstein CS (1986) The influence of pressure overload left ventricular hypertrophy on diastolic properties during hypoxia in isovolumically contracting rat hearts. Circ Res 58:653–663
Mercadier JJ, Lompré AM, Due P, Boheler KR, Fraysse JB, Wisnewsky C, Allen P, Komajda M, Schwartz K (1990) Altered sarcoplasmic reticulum Ca2+-ATPase gene expression in the human ventricle during end stage heart failure. J Clin Invest 85:305–309
Morgan JP (1991) Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 325:625–632
Mulieri LA, Hasenfuss G, Leavitt B, Allen PD, Alpert NR (1992) Altered myocardial force-frequency relation in human heart failure. Circulation 85:1743–1750
Nadal-Ginard B, Mahdavi V (1990) Molecular basis of cardiac performance. J Clin Invest 84:1693–1700
Nagai R, Zarain-Herzberg A, Brandi CJ, Fuji J, Tada M, MacLennan DH, Alpert NR, Periasamy M (1989) Regulation of myocardial Ca2 +-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc Natl Acad Sei USA 86:2966–2970
Nagano M, Higaki J, Mikami H, Nakamaru M, Higashimori K, Katahira K, Tabuchi Y, Nakamura F, Ogihara T (1991) converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats. J Hypertens 9:595–599
Nagano M, Higaki J, Nakamura F, Higashimori K, Nagano N, Mikami H, Ogihara T (1992) Role of cardiac angiotensin II in isoprotenol-induced left ventricular hypertrophy.
Perondi R, Saino A, Tio RA, Pomidossi G, Gregorini L, Alessio P, Morganti A, Zanchetti A, Mancia G (1992) ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Circulation 85:2004–2013
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 79:3310–3314
Philipson KD (1992) Cardiac sodium-calcium exchange research. Trends Cardiovasc Med 2:12–14
Reinecke H, Bilger J, Hollmann A, Holtz J, Just H, Müller B, Philipson KD, Studer R, Drexler H (1992) Veränderung der Genexpression von SR-Ca2+ -ATPase und Na+/Ca2+ -Exchanger im Restmyokard nach Infarkt bei der Ratte. Z Kardiol 81 (Suppl. 1): 113
Reinecke H, Studer R, Goetz RM, Drexler H, Just H, Holtz J (1992) Die Genexpression der SR-Ca++-ATPase und des Connexin-43 bei kompensierter linksventrikulärer Hypertrophie (LVH) ist nur vorübergehend vermindert. Z Kardiol 81 (Suppl. 1): 120
Reinecke H, Studer R, Philipson KD, Bilger J, Eschenhagen T, Böhm M, Just H, Holtz J, Drexler H (1992) Myocardial gene expression of Na+/Ca++-exchanger and sarcoplasmic reticulum Ca++-ATPase in human heart failure. Circulation (in press)
Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH (1990) Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. J Clin Invest 86:1913–1920
Schwartz K, Mercadier JJ, Swynghedauw B, Lompre AM (1988) Modifications of gene expression in cardiac hypertrophy. Heart Failure 4:154–163
Silverberg JS, Barre PE, Prichard SS, Sniderman AD (1989) Impact of left ventricular hypertrophy on survival in end-stage renal disease. Kidney Int 36:286–290
Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT (1991) Cardiac myocyte necrosis induced by angiotensin II. Circ Res 69:1185–1195
Ten Eick RE, Whalley DW, Rasmussen HH (1992) Connections: heart disease, cellular electrophysiology, and ion channels. FASEB J 6:2568–2580
Urata H, Healy B, Stewart RW, Bumpus FM, Husain A (1990) Angiotensin II-forming pathways in normal and failing human hearts. Circ Res 66:883–890
Urata H, Kinoshita A, Misono KS, 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
Urata H, Kinoshita A, Perez DM, Misono KS, Bumpus FM, Graham RM, Husain A (1991) Cloning of the gene and cDNA for human heart chymase. J Biol Chem 266:17173–17179
van Gilst WH, de Graeff PA, Wesseling H, de Langen CDJ (1986) Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of Captopril, enalapril and Hoe 498. J Cardiovasc Pharmacol 8:722–728
Wiemer G, Schölkens BA, Becker RH A, Busse R (1991) Ramipril enhances endothelial autocoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension 18:558–563
Wier WG (1990) Cytoplasmic Ca++ in mammalian ventricle: dynamic control by cellular processes. Ann Rev Physiol 52:467–485
Wirth K, Hock FJ, Albus U, Linz W, Anagnostopoulos H, Henke ST, Breipohl G, König W, Knolle J, Schölkens BA (1991) Hoe 140 a new potent and long acting bradykinin-antagonist: In vivo studies. Br J Pharmacol 102:774–777
Xiang JZ, Linz W, Becker H, Ganten D, Lang RE, Schölkens B, Unger T (1985) Effects of converting enzyme inhibitors: ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart. Eur J Pharmacol 113:215–223
Yamada H, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn FAO (1991) Localization of angiotensin converting enzyme in rat heart. Circ Res 68:141–149
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© 1992 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt
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Holtz, J., Studer, R., Reinecke, H., Just, H., Drexler, H. (1992). Modulation of myocardial sarcoplasmic reticulum Ca++-ATPase in cardiac hypertrophy by angiotensin converting enzyme?. In: Holtz, J., Drexler, H., Just, H. (eds) Cardiac Adaptation in Heart Failure. Steinkopff. https://doi.org/10.1007/978-3-642-72477-0_17
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DOI: https://doi.org/10.1007/978-3-642-72477-0_17
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