Skip to main content
SpringerLink
Log in

Losartan inhibits myosin isoform shift after myocardial infarction in rats

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

Abstract

Hypertrophy and heart failure following a myocardial infarction in rodents are accompanied by a switch of myosin isoforms from V1 to V3. The angiotensin II receptor blocker, Losartan, has been demonstrated to improve cardiac function and long-term survival after myocardial infarction. In this study we have investigated whether chronic Losartan treatment affects myosin isoform composition in the hearts of rats following a myocardial infarction. Rats were subjected to coronary artery ligation and received either Losartan (1 g/L) in the drinking water or water only. Four months after myocardial infarction, rats were classified as having either congestive heart failure (cMI) or uncomplicated myocardial infarction (uMI) based on their lung weight to body weight ratio (LW/BW). Compared with sham operated rats, uMI rats showed a 68.5% increase in the relative contribution of V3 and a 33.7% decrease in the relative contribution of V1 (p < 0.05). Untreated cMI showed 39.7% more V3 and 38.2% less V1 when compared with untreated uMI (p < 0.05). Losartan treatment after myocardial infarction reduced the incidence of cMI from 30.4 to 4.5% and scar size from 1.52 ± 0.07 to 0.94 ± 0.11 cm2 respectively. The percentage of V1 in Losartan treated uMI (LuMI) was 25.2% higher than the percentage of V1 in untreated uMI (p < 0.05), whereas the percentage of V3 in LuMI was 24.2% lower than that in untreated uMI (p < 0.05). A positive correlation of V3 myosin and scar area was observed. Our study suggests that expression of V3 myosin in the left ventricle is associated with scar size and the progress of hemodynamic changes after myocardial infarction. Losartan treatment reduces scar size and wall stress of the heart after the infarct, and therefore inhibits the signals shifting myosin isoform expression from V1 to V3 after a myocardial infarction.

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. Hoh JF, McGrath PA, Hale PT: Electrophoretic analysis of multiple forms of rat cardiac myosin: Effects of hypophysectomy and thyroxine replacement. J Mol Cell Cardiol 10: 1053-1076, 1978

    Google Scholar 

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

    Google Scholar 

  3. Lompre AM, Nadal-Ginard B, Mahdavi V: Expression of the cardiac ventricular alpha-and beta-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem 259: 6437-6446, 1984

    Google Scholar 

  4. Martin AF, Robinson DC, Dowell RT: Isomyosin and thyroid hormone levels in pressure-overloaded weanling and adult rat hearts. Am J Physiol 248: H305-H310, 1985

    Google Scholar 

  5. Haddad F, Bodell PW, Baldwin KM: Pressure-induced regulation of myosin expression in rodent heart. J Appl Physiol 78: 1489-1495, 1995

    Google Scholar 

  6. Yue P, Long CS, Austin R, Chang KC, Simpson PC, Massie BM: Post-infarction heart failure in the rat is associated with distinct alterations in cardiac myocyte molecular phenotype. J Mol Cell Cardiol 30: 1615-1630, 1998

    Google Scholar 

  7. Dorn GW, Robbins J, Ball N, Walsh RA: Myosin heavy chain regulation and myocyte contractile depression after LV hypertrophy in aortic-banded mice. Am J Physiol 267: H400-H405, 1994

    Google Scholar 

  8. Reddy DS, Singh M, Ghosh S, Ganguly NK: Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction. Mol Cell Biochem 155: 1-11, 1996

    Google Scholar 

  9. Baker KM, Booz GW, Dostal DE: Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol 54: 227-241, 1992

    Google Scholar 

  10. Sadoshima J, Jahn L, Takahashi T, Kulik TJ, Izumo S: Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J Biol Chem 267: 10551-10560, 1992

    Google Scholar 

  11. Sadoshima J, Izumo S: 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, 1993

    Google Scholar 

  12. Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, Takaku F, Yazaki Y: Stretching cardiac myocytes stimulates proto-oncogene expression. J Biol Chem 265: 3595-3598, 1990

    Google Scholar 

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

    Google Scholar 

  14. Yamagishi H, Kim S, Nishikimi T, Takeuchi K, Takeda T: Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats. J Mol Cell Cardiol 25: 1369-1380, 1993

    Google Scholar 

  15. Richer C, Fornes P, Cazaubon C, Domergue V, Nisato D, Giudicelli JF: Effects of long-term angiotensin II AT1 receptor blockade on survival, hemodynamics and cardiac remodeling in chronic heart failure in rats (see comments). Cardiovasc Res 41: 100-108, 1999

    Google Scholar 

  16. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, Deedwania PC, Ney DE, Snavely DB, Chang PI: Randomised trial of Losartan vs. captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE) (see comments). Lancet 349: 747-752, 1997

    Google Scholar 

  17. Xia QG, Chung O, Spitznagel H, Sandmann S, Illner S, Rossius B, Jahnichen G, Reinecke A, Gohlke P, Unger T: Effects of a novel angiotensin AT(1) receptor antagonist, HR720, on rats with myocardial infarction. Eur J Pharmacol 385: 171-179, 1999

    Google Scholar 

  18. Davidoff AW: Congestive heart failure in the rats. Thesis, University of Calgary, 1998, pp 40-48

  19. Johns TNP, Olson BJ: Experimental myocardial infarction. I. A method of coronary occlusion in small animals. Ann Surg 140: 675-682, 1954

    Google Scholar 

  20. Hoh JY, McGrath PA, White RI: Electrophoretic analysis of multiple forms of myosin in fast-twitch and slow-twitch muscles of the chick. Biochem J 157: 87-95, 1976

    Google Scholar 

  21. Schwartz K, Lecarpentier Y, Martin JL, Lompre AM, Mercadier JJ, Swynghedauw B: Myosin isoenzymic distribution correlates with speed of myocardial contraction. J Mol Cell Cardiol 13: 1071-1075, 1981

    Google Scholar 

  22. Alpert NR, Mulieri LA: Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary artery constriction in the rabbit. A characterization of heat liberation in normal and hypertrophied right ventricular papillary muscles. Circ Res 50: 491-500, 1982

    Google Scholar 

  23. Kissling G, Rupp H, Malloy L, Jacob R: Alterations in cardiac oxygen consumption under chronic pressure overload. Significance of the isoenzyme pattern of myosin. Basic Res Cardiol 77: 255-269, 1982

    Google Scholar 

  24. Xiang JZ, Linz W, Becker H, Ganten D, Lang RE, Scholkens B, Unger T: Effects of converting enzyme inhibitors: Ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart. Eur J Pharmacol 113: 215-223, 1985

    Google Scholar 

  25. Katz AM: Potential deleterious effects of inotropic agents in the therapy of chronic heart failure. Circulation 73: III184-III190, 1986

    Google Scholar 

  26. Sadoshima J, Xu Y, Slayter HS, Izumo S: Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75: 977-984, 1993

    Google Scholar 

  27. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, Malhotra A, Kajstura J, Anversa P: Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest 101: 1326-1342, 1998

    Google Scholar 

  28. Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT: Cardiac myocyte necrosis induced by angiotensin II. Circ Res 69: 1185-1195, 1991

    Google Scholar 

  29. Childs TJ, Adams MA, Mak AS: Regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril and the expression of contractile proteins. Hypertension 16: 662-668, 1990

    Google Scholar 

  30. Kojima M, Shiojima I, Yamazaki T, Komuro I, Zou Z, Wang Y, Mizuno T, Ueki K, Tobe K, Kadowaki T: Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation 89: 2204-2211, 1994

    Google Scholar 

  31. Michel JB, Lattion AL, Salzmann JL, Cerol ML, Philippe M, Camilleri JP, Corvol P: Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction. Circ Res 62: 641-650, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine and Physiology and Biophysics, Faculty of Medicine, University Calgary, Calgary, Alberta, Canada

    Mei Luo Zhang, Samer Elkassem, Allen W. Davidoff, Kaoru Saito & Henk E.D.J. ter Keurs

Authors
  1. Mei Luo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samer Elkassem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Allen W. Davidoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaoru Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henk E.D.J. ter Keurs
    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

Zhang, M.L., Elkassem, S., Davidoff, A.W. et al. Losartan inhibits myosin isoform shift after myocardial infarction in rats. Mol Cell Biochem 251, 111–117 (2003). https://doi.org/10.1023/A:1025494218689

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025494218689

Search

Navigation