Skip to main content
SpringerLink
Log in

Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The effects of propranolol and verapamil on contractile dysfunction, subcellular remodeling and changes in gene expression in cardiac hypertrophy due to pressure overload were examined. Rats were subjected to banding of the abdominal aorta and then treated with either propranolol (10 mg/kg daily), verapamil (5 mg/kg daily) or vehicle for 8 weeks after the surgery. Depression of the left ventricular function in the hypertrophied heart was associated with decreases in myofibrillar and myosin CA2+ ATPase activities as well as Ca2+-pump and Ca2+-release activities of the sarcoplasmic reticulum (SR). The level of a-myosin heavy chain (α-MHC) mRNA was decreased while that of β-MHC mRNA was increased in the pressure-overloaded heart. The level of SR Ca2+-pump ATPase (SERCA2) mRNA and protein content for SERCA2 were decreased in the pressure overloaded heart. Treatment of the hypertrophied animals with propranolol or verapamil resulted in preservation of the left ventricular function and prevention of the subcellular alterations. Shift in the α- and β-MHC mRNA levels and changes in the expression in SERCA2 mRNA level and protein content were also attenuated by these treatments. The results suggest that blockade of β-adrenoceptors or voltage-dependent calcium channels normalizes the cardiac gene expression, prevents subcellular remodeling and thus attenuates heart dysfunction in rats with cardiac hypertrophy. Furthermore, both cardiac β-adrenoceptors and L-type Ca2+-channels may be involved in the genesis of cardiac hypertrophy due to pressure overload.

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. Tsoporis J, Leenen FH: Effects of arterial vasodilators on cardiac hypertrophy and sympathetic activity in rats. Hypertension 11: 376-386, 1988

    Google Scholar 

  2. Linz W, Scholkens BA, Ganten D: Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens 11: 1325-1350, 1989

    Google Scholar 

  3. Nguyen T, El Salibi E, Rouleau JL: Postinfarction survival and inducibility of ventricular arrhythmias in the spontaneously hypertensive rat: Effects of ramipril and hydralazine. Circulation 98: 2074-2080, 1998

    Google Scholar 

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

    Google Scholar 

  5. Natsume T: Therapeutic advances in the treatment of left ventricular hypertrophy. Eur Heart J 14(suppl D): 33-37, 1993

    Google Scholar 

  6. Chiba K, Moriyama S, Ishigai Y, Fukuzawa A, Irie K, Shibano T: Lack of correlation of hypotensive effects with prevention of cardiac hypertrophy by perindopril after ligation of rat coronary artery. Br J Pharmacol 112: 837-842, 1994

    Google Scholar 

  7. Sen S, Young D: Effect of antihypertensive therapy upon myosin isozyme distribution in spontaneously hypertensive rats. J Hypertens 10: 749-756, 1992

    Google Scholar 

  8. Dahlof B, Pennert K, Hansson L: Regression of left ventricular hypertrophy–a meta-analysis. Clin Exp Hypertens 14: 173-180, 1992

    Google Scholar 

  9. Kromer EP, Elsner D, Riegger GA: Role of neurohumoral systems for pressure induced left ventricular hypertrophy in experimental supravalvular aortic stenosis in rats. Am J Hypertens 4: 521-524, 191

  10. Hansson L: Reversal of cardiac and vascular hypertrophy by antihypertensive therapy. Am Heart J 121: 995-998, 1991

    Google Scholar 

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

    Google Scholar 

  12. Litwin SE, Katz SE, Weinberg EO, Lorell BH, Aurigemma GP, Douglas PS: Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure. Circulation 91: 2642-2654, 1995

    Google Scholar 

  13. Tarazi RC, Sen S, Saragoca M, Khairallah P: The multifactorial role of catecholamines in hypertensive cardiac hypertrophy. Eur Heart J 3(suppl A): 103-110, 1982

    Google Scholar 

  14. Lindpaintner K, Ganten D: The cardiac renin-angiotensin system. An appraisal of present experimental and clinical evidence. Circ Res 68: 905-921, 1991

    Google Scholar 

  15. Holtz J, Studer R, Reinecke H, Just H, Drexler H: Modulation of myocardial sarcoplasmic reticulum Ca2+-ATPase in cardiac hypertrophy by angiotensin converting enzyme? Basic Res Cardiol 87(suppl 2): 191-204, 1992

    Google Scholar 

  16. Anger M, Lambert F, Chemla D, Desche P, Scalbert E, Lompre AM, Lecarpentier Y: Sarcoplasmic reticulum Ca2+ pumps in heart and diaphragm of cardiomyopathic hamster: Effects of perindopril. AM J Physiol 268: H1947-H1953, 1995

    Google Scholar 

  17. Zierhut W, Studer R, Laurent D, Kastner S, Allegrini P, Whitebread S, Cumin F, Baum HP, de Gasparo M, Drexler H: Left ventricular wall stress and sarcoplasmic reticulum Ca2+-ATPase gene expression in renal hypertensive rats: Dose-dependent effects of ACE inhibition and AT1-receptor blockade. Cardiovasc Res 31: 758-768, 1996

    Google Scholar 

  18. Flesch M, Schiffer F, Zolk O, Pinto Y, Stasche JP, Knorr A, Ettelbruck S, Bohm M: Angiotensin receptor antagonism and angiotensin converting enzyme inhibition improve diastolic dysfunction and Ca2+-ATPase expression in the sarcoplasmic reticulum in hypertensive cardiomyopathy. J Hypertens 15: 1001-1009, 1997

    Google Scholar 

  19. Yoshiyama M, Takeuchi K, Hanatani A, Shimada T, Takemoto Y, Shimizu N, Omura T, Kim S, Iwao H, Yoshikawa J: Effect of cilazapril on ventricular remodeling assessed by Doppler-echocardiographic assessment and cardiac gene expression. Cardiovasc Drugs Ther 12: 57-70, 1998

    Google Scholar 

  20. Donohue TJ, Dworkin LD, Ma J, Lango MN, Catanese VM: Antihypertensive agents that limit ventricular hypertrophy inhibit cardiac expression of insulin-like growth factor-I. J Invest Med 45: 584-591, 1997

    Google Scholar 

  21. Katz AM: Cell death in the failing heart: Role of an unnatural growth response to overload. Clin Cardiol 18: IV36-IV44, 1995

    Google Scholar 

  22. Morgan JP: Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 325: 625-632, 1991

    Google Scholar 

  23. Dhalla NS, Golfman L, Liu X, Sasaki H, Elimban V, Rupp H: Subcellular remodeling and heart dysfunction in cardiac hypertrophy due to pressure overload. Ann NY Acad Sci 874: 100-110, 1999

    Google Scholar 

  24. Liu X, Sentex E, Golfman L, Takeda S, Osada M, Dhalla NS: Modification of cardiac subcellular remodeling due to pressure overload by captopril and losartan. Clin Exp Hypertens 21: 145-156, 1999

    Google Scholar 

  25. Zarain-Herzberg A, Rupp H, Elimban V, Dhalla NS: Modification of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomoxir. FASEB J 10: 1303-1309, 1996

    Google Scholar 

  26. Dixon IMC, Lee SL, Dhalla NS: Nitrendipine binding in congestive heart failure due to myocardial infarction. Circ Res 66: 782-788, 1990

    Google Scholar 

  27. Ganguly PK, Pierce GN, Dhalla KS, Dhalla NS: Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol 244: E528-E535, 1983

    Google Scholar 

  28. Pierce GN, Dhalla NS: Mechanisms of the defect in cardiac myofibrillar function during diabetes. Am J Physiol 248: E170-E175, 1985

    Google Scholar 

  29. Afzal N, Dhalla NS: Differential changes in left and right ventricular SR calcium transport in congestive heart failure. Am J Physiol 262: H868-H874, 1992

    Google Scholar 

  30. Osada M, Netticadan T, Tamura K, Dhalla NS: Modification of ischemiareperfusion-induced changes in cardiac sarcoplasmic reticulum by preconditioning. Am J Physiol 274: H2025-H2034, 1998

    Google Scholar 

  31. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156-159, 1987

    Google Scholar 

  32. Ju H, Scammel-La Fleur T, Dixon IMC: Altered mRNA abundance of calcium transport genes in cardiac myocytes induced by angiotensin II. J Mol Cell Cardiol 28: 1119-1128, 1996

    Google Scholar 

  33. Schwartz K, Lompre AM, Bouveret P, Wisnewsky C, Whalen RG: Comparisons of rat cardiac myosins at fetal stages in young animals and in hypothyroid adults. J Biol Chem 257: 14412-14418, 1982

    Google Scholar 

  34. Arai M, Matsui H, Periasamy M: Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res 74: 555-564, 1994

    Google Scholar 

  35. de la BD, Levitsky D, Rappaport L, Mercadier JJ, Marotte F, Wisnewsky C, Brovkovich V, Schwartz K, Lompre AM: 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, 1990

    Google Scholar 

  36. Feldman AM, Weinberg EO, Ray PE, Lorell BH: Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ Res 73: 184-192, 1993

    Google Scholar 

  37. Ohta K, Kim S, Iwao H: Role of angiotensin-converting enzyme, adrenergic receptors, and blood pressure in cardiac gene expression of spontaneously hypertensive rats during development. Hypertension 28: 627-634, 1996

    Google Scholar 

  38. Breisch EA, White FC, Bloor CM: Myocardial characteristics of pressure overload hypertrophy. A structural and functional study. Lab Invest 51: 333-342, 1984

    Google Scholar 

  39. Brilla CG, Janicki JS, Weber KT: Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medical thickening of intramyocardial coronary arteries. Circ Res 69: 107-115, 1991

    Google Scholar 

  40. Mercadier JJ, Lompre AM, Wisnewsky C, Samuel JL, Bercovici J, Swynghedauw B, Schwartz K: Myosin isoenzyme changes in several models of rat cardiac hypertrophy. Circ Res 49: 525-532, 1981

    Google Scholar 

  41. Gorza L, Pauletto P, Pessina AC, Sartore S, Schiaffino S: Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study. Circ Res 49: 1003-1009, 1981

    Google Scholar 

  42. Lompre AM, Schwartz K, d'Albis A, Lacombe G, Van Thiem N, Swynghedauw B: Myosin isoenzyme redistribution in chronic heart overload. Nature 282: 105-107, 1979

    Google Scholar 

  43. Izumo S, Lompre AM, Matusoka R, Koren G, Schwartz K, Nadal-Ginard B, Mahdavi V: Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals. J Clin Invest 79: 970-977, 1987

    Google Scholar 

  44. Pope B, Hoh JF, Weeds A: The ATPase activities of rat cardiac myosin isoenzymes. FEBS Lett 118: 205-208, 1980

    Google Scholar 

  45. Messerli FH, Oren S, Grossman E: Left ventricular hypertrophy and antihypertensive therapy. Drugs 35(suppl 5): 27-33, 1988

    Google Scholar 

  46. Schmieder RE, Martus P, Klingbeil A: Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA 275: 1507-1513, 1996

    Google Scholar 

  47. Bertram D, Barres C, Cuisinaud G, Julien C: The arterial baroreceptor reflex of the rat exhibits positive feedback properties at the frequency of mayer waves. J Physiol (Lond) 513: 251-261, 1998

    Google Scholar 

  48. Devereux RB: Therapeutic options in minimizing left ventricular hypertrophy. Am Heart J 139: S9-S14, 2000

    Google Scholar 

  49. Chien KR, Knowlton KU, Zhu H, Chien S: Regulation of cardiac gene expression during myocardial growth and hypertrophy: Molecular studies of an adaptive physiologic response. FASEB J 5: 3037-3046, 1991

    Google Scholar 

  50. Rupp H, Jacob R: Response of blood pressure and cardiac myosin polymorphism to swimming training in the spontaneously hypertensive rat. Can J Physiol Pharmacol 60: 1098-1103, 1982

    Google Scholar 

  51. Newton GE, Parker JD: Acute effects of beta 1-selective and nonselective beta-adrenergic receptor blockade on cardiac sympathetic activity in congestive heart failure. Circulation 94: 353-358, 1996

    Google Scholar 

  52. Lucas PC, Granner DK: Hormone response domains in gene transcription. Annu Rev Biochem 61: 1131-1173, 1992

    Google Scholar 

  53. Papavassiliou AG: Molecular medicine. Transcription factors. N Engl J Med 332: 45-47, 1995

    Google Scholar 

  54. Leenen FH, Holliwell DL: Antihypertensive effect of felodipine associated with persistent sympathetic activation and minimal regression of left ventricular hypertrophy. Am J Cardiol 69: 639-645, 1992

    Google Scholar 

  55. Friberg P, Folkow B, Nordlander M: Cardiac dimensions in spontaneously hypertensive rats following different modes of blood pressure reduction by antihypertensive treatment. J Hypertens 4: 85-92, 1986

    Google Scholar 

  56. Feron O, Salomone S, Godfraind T: Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin-1 gene expression in stroke-prone hypertensive rats. Br J Pharmacol 118: 659-664, 1996

    Google Scholar 

  57. Boluyt MO, O'Neill L, Meredith AL, Bing OH, Brooks WW, Conrad CH, Crow MT, Lakatta EG: Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. Circ Res 75: 23-32, 1994

    Google Scholar 

  58. Komuro I, Kurabayashi M, Takaku F, Yazaki Y: Expression of cellular oncogenes in the myocardium during the developmental stage and pressure-overloaded hypertrophy of the rat heart. Circ Res 62: 1075-1079, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Tokyo College of Pharmacy, Tokyo, Japan

    Satoshi Takeo

  2. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Canada

    Adel B. Elmoselhi, Raj Goel, Emmanuelle Sentex, Jingwei Wang & Naranjan S. Dhalla

  3. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Adel B. Elmoselhi, Raj Goel, Emmanuelle Sentex & Jingwei Wang

  4. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla

Authors
  1. Satoshi Takeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adel B. Elmoselhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raj Goel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emmanuelle Sentex
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jingwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naranjan S. Dhalla
    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

Takeo, S., Elmoselhi, A.B., Goel, R. et al. Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil. Mol Cell Biochem 213, 111–118 (2000). https://doi.org/10.1023/A:1007120332587

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007120332587

Search

Navigation