Pflügers Archiv

, Volume 336, Issue 4, pp 311–325 | Cite as

Changes of protein synthesis in the hypertrophying rat heart

  • Heinz-Gerd Zimmer
  • Gudrun Steinkopff
  • Eckehart Gerlach


Myocardial protein synthesis was studied in rats in vivo during the first five days of the development of cardiac hypertrophy induced by aortic constriction. Using l-14C-glycine or l-14C-leucine as precursor amino acids, rates of protein synthesis were determined from the total radioactivity of proteins and the mean radioactivity of the intracellular amino acid precursor pool and the leucine pool, respectively. During the first 5 h after aortic constriction the radioactivity of proteins did not change remarkably, whereas the radioactivity of the amino acid precursor pool was significantly elevated. Myocardial protein synthesis proved therefore to be diminished in this initial phase. After 24 h protein synthesis reached the range of sham-operated controls and thereafter increased almost parallel with the elevation of the ratio heart weight/body weight. The inhibition of protein synthesis was accompanied by a moderate decrease of ATP and creatine phosphate levels. A diminution of the high energy phosphate compounds, a decreased RNA synthesis or the action of inhibitory metabolites are considered possible factors involved in the decline of protein synthesis during the early phase of cardiac hypertrophy.

Key words

Aortic Constriction Cardiac Hypertrophy Amino Acid Incorporation Protein Synthesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arvill, A.: Relationship between the effects of contraction and insulin on the metabolism of the isolated levator ani muscle of the rat. Acta endocr. (Kbh.)56, 27–41 (1967).Google Scholar
  2. 2.
    Bachrach, U., Abzug, S., Bekierkunst, A.: Cytotoxic effect of oxidized spermine on Ehrlich ascites cells. Biochim. biophys. Acta (Amst.)134, 174–181 (1967).Google Scholar
  3. 3.
    Beznak, M.: Cardiac output in rats during the development of cardiac hypertrophy. Circulat. Res.6, 207–212 (1958).Google Scholar
  4. 4.
    Büchner, F.: Herzhypertrophie und Herzinsuffizienz in der Sicht der modernen Pathologie. Dtsch. med. Wschr.96, 1–7 (1971).Google Scholar
  5. 5.
    Büchner, F., Onishi, S.: Herzhypertrophie und Herzinsuffizienz in der Sicht der Elektronenmikroskopie. München-Berlin-Wien: Urban & Schwarzenberg (1970).Google Scholar
  6. 6.
    Caldarera, C. M., Casti, A., Rossoni, C., Visioll, O.: Polyamines and noradrenaline following myocardial hypertrophy. J. molec. Cell. Cardiol.3, 121–126 (1971).Google Scholar
  7. 7.
    Cohen, J., Feldman, R. E., Whitbeck, A. A.: Effects of energy availability on protein synthesis in isolated rat atria. Amer. J. Physiol.216, 76–81 (1969).Google Scholar
  8. 8.
    Fanburg, B. L., Posner, B. I.: Ribonucleic acid synthesis in experimental cardiac hypertrophy in rats. I. Characterization and kinetics of labeling. Circulat. Res.23, 123–135 (1968).Google Scholar
  9. 9.
    Florini, J. R., Dankberg, F. L.: Changes in ribonucleic acid and protein synthesis during induced cardiac hypertrophy. Biochemistry10, 530–535 (1971).Google Scholar
  10. 10.
    Freudenberg, H., Mager, J.: Studies on the mechanism of the inhibition of protein synthesis induced by intracellular ATP depletion. Biochim. biophys. Acta (Amst.)232, 537–555 (1971).Google Scholar
  11. 11.
    Gerlach, E., Deuticke, B., Dreisbach, R. H., Rosarius, C. W.: Zum Verhalten von Nucleotiden und ihren dephosphorylierten Abbauprodukten in der Niere bei Ischämie und kurzzeitiger post-ischämischer Wiederdurchblutung. Pflügers Arch. ges. Physiol.278, 296–315 (1963).Google Scholar
  12. 12.
    Gerlach, E., Janke, J.: Papierchromatographische Bestimmung von Kreatinphosphat und Orthophosphat in Gewebsextrakten. Biochem. Z.330, 565–575 (1958).Google Scholar
  13. 13.
    Gerlach, E., Marko, P., Zimmer, H.-G., Pechan, I., Trendelenburg, Chr.: Different response of adenine nucleotide synthesis de novo in kidney and brain during aerobic recovery from anoxia and ischemia. Experientia (Basel)27, 876–878 (1971).Google Scholar
  14. 14.
    Gerlach, E., Zimmer, H.-G.: Protein- und Nucleotid-Synthese im hypertrophierenden Herzmuskel. Verh. dtsch. Ges. Kreisl.-Forsch.38 (in press.)Google Scholar
  15. 15.
    Goldberg, A. L., Goodman, H. M.: Amino acid transport during work-induced growth of skeletal muscle. Amer. J. Physiol.216, 1111–1115 (1969).Google Scholar
  16. 16.
    Gubjarnason, S., Telerman, M., Bing, R. J.: Protein metabolism in cardiac hypertrophy and heart failure. Amer. J. Physiol.206, 294–298 (1964).Google Scholar
  17. 17.
    Hider, R. C., Fern, E. B., London, D. R.: Relationship between intracellular amino acids and protein synthesis in the extensor digitorum longus muscle of rats. Biochem. J.114, 171–178 (1969).Google Scholar
  18. 18.
    Jefferson, L. S., Wolpert, E. B., Giger, K. E., Morgan, H. E.: Regulation of protein synthesis in heart muscle. III. Effect of anoxia on protein synthesis. J. biol. Chem.246, 2171–2178 (1971).Google Scholar
  19. 19.
    Karpatkin, S., Samuels, A.: Effect of insulin and muscle contraction on protein synthesis in frog sartorius. Arch. Biochem.121, 695–702 (1967).Google Scholar
  20. 20.
    Koide, T., Rabinowitz, M.: Biochemical correlates of cardiac hypertrophy. II. Increased rate of RNA synthesis in experimental cardiac hypertrophy in the rat. Circulat. Res.24, 9–18 (1969).Google Scholar
  21. 21.
    Lesch, M., Gorlin, R., Sonnenblick, E. H.: Myocardial amino acid transport in the isolated rabbit right ventricular papillary muscle. Circulat. Res.27, 445–460 (1970).Google Scholar
  22. 22.
    Malamud, D., Baserga, R.: Pool size and specific activity of UTP in isoproterenol-stimulated salivary glands. Biochim. biophys. Acta (Amst.)195, 258–261 (1969).Google Scholar
  23. 23.
    Mallov, S., Alousi, A. A.: Effect of altered cardiac metabolism and work on lipoprotein lipase activity of heart. Amer. J. Physiol.212, 1158–1164 (1967).Google Scholar
  24. 24.
    Marko, P., Zimmer, H.-G., Gourley, D. R. H., Gerlach, E.: Different behaviour of3H-glycine and14C-glycine in studies of mammalian tissue metabolism. Experientia (Basel)26, 951–952 (1970).Google Scholar
  25. 25.
    Meerson, F. Z.: Compensatory hyperfunction of the heart and cardiac insufficiency. Circulat Res.10, 250–258 (1962).Google Scholar
  26. 26.
    Meerson, F. Z.: The myocardium in hyperfunction, hypertrophy and heart failure, Circulat. Res.15, (Suppl. II), 1–163 (1969).Google Scholar
  27. 27.
    Minelli, R., Kako, K. J., Macdonald, M. M.: The relationship between amino acid incorporation and cardiac work level in the rat heart-lung preparation. Naunyn-Schmiedebergs Arch. Pharmak.264, 119–128 (1969).Google Scholar
  28. 28.
    Margon, H. E., Earl, D. C. N., Broadus, A., Wolpert, E. B., Giger, K. E., Jefferson, L. S.: Regulation of protein synthesis in heart muscle. I. Effect of amino acid levels on protein synthesis. J. biol. Chem.246, 2152–2162 (1971).Google Scholar
  29. 29.
    Moroz, L. A.: Protein synthetic activity of heart microsomes and ribosomes during left ventricular hypertrophy in rabbits. Circulat. Res.21, 449–459 (1967).Google Scholar
  30. 30.
    Nair, K. G., Cutiletta, A. F., Zak, R., Koide, T., Rabinowitz, M.: Biochemical correlates of cardiac hypertrophy. I. Experimental model; changes in heart weight, RNA content, and nuclear RNA polymerase activity. Circulat. Res.23, 451–462 (1968).Google Scholar
  31. 31.
    Pain, V. M., Manchester, K. L.: The influence of electrical stimulation in vitro on protein synthesis and other metabolic parameters of rat extensor digitorum longus muscle. Biochem. J.118, 209–220 (1970).Google Scholar
  32. 32.
    Posner, B. I., Fanburg, B. L.: Ribonucleic acid synthesis in experimental cardiac hypertrophy in rats. II. Aspects of regulation. Circulat. Res.23, 137–145 (1968).Google Scholar
  33. 33.
    Schreiber, S. S., Evans, C., Oratz, M., Rothschild, M. A.: Effect of hyperbaric oxygen on protein synthesis in the mammalian heart. Amer. J. Physiol.212, 35–38 (1967).Google Scholar
  34. 34.
    Schreiber, S. S., Oratz, M., Evans, C. D., Gueyikian, I., Rothschild, M. A.: Myosin, myoglobin, and collagen synthesis in acute cardiac overload. Amer. J. Physiol.219, 481–486 (1970).Google Scholar
  35. 35.
    Schreiber, S. S., Oratz, M., Rothschild, M. A.: Protein synthesis in the overloaded mammalian heart. Amer. J. Physiol.211, 314–318 (1966).Google Scholar
  36. 36.
    Schreiber, S. S., Oratz, M., Rothschild, M. A.: Effect of acute overload on protein synthesis in cardiac muscle microsomes. Amer. J. Physiol.213, 1552–1555 (1967).Google Scholar
  37. 37.
    Springfellow, C., Brachfeld, N.: A study of transfer RNA, total RNA and protein interrelationships in control and stressed isolated perfused rat hearts. J. molec. Cell. Cardiol.1, 221–233 (1970).Google Scholar
  38. 38.
    Steele, W. J., Okamura, N., Busch, H.: Prevention of loss of RNA, DNA and protein into lipid solvent. Biochim. biophys. Acta (Amst.)87, 490–492 (1964).Google Scholar
  39. 39.
    Vetter, J., Brade, W.: Steigerung der ribosomalen Proteinsynthese in Rattennieren nach hohen Folsäuregaben. Naunyn-Schmiedebergs Arch. Pharmak.269, 462 (1971).Google Scholar
  40. 40.
    Wannemacher, R. W., McCoy, J. R.: Regulation of protein synthesis in the ventricular myocardium of hypertrophic hearts. Amer. J. Physiol.216, 781–787 (1969).Google Scholar
  41. 41.
    Zamecnik, P. C.: An historical account of protein synthesis, with current overtones—a personalized view. Cold Spring Harb. Symp. quant. Biol.24, 1–16 (1969).Google Scholar
  42. 42.
    Zimmer, H.-G., Marko, P., Kammermeier, H., Schwarzmeier, J., Krautzberger, W., Gourley, D. R. H., Gerlach, E.: Synthesis of nucleotides and proteins in the heart during pressure load and hypertrophy. Pflügers Arch.312, R 12 (1969).Google Scholar
  43. 43.
    Zimmer, H.-G., Rainer, H., Gerlach, E.: Time course of changes of protein synthesis in the hypertrophying rat heart. Proc. Intern. Un. Physiol. Sci9, 619 (1971).Google Scholar
  44. 44.
    Zimmer, H.-G., Schwarzmeier, J., Marko, P., Gerlach, E.: The effect of acute exercise on protein synthesis in heart and skeletal muscle of rats. Pflügers Arch.319, R 11 (1970).Google Scholar
  45. 45.
    Zimmer, H.-G., Trendelenburg, Chr., Gerlach, E.: Acceleration of adenine nucleotide synthesis de novo during development of cardiac hypertrophy. J. molec. Cell. Cardiol.4, 279 (1972).Google Scholar
  46. 46.
    Zühlke, V., du Mesnil de Rochemont, W., Gudbjarnason, S., Bing, R. J.: Inhibition of protein synthesis in cardiac hypertrophy and its relation to myocardial failure. Circulat. Res.28, 558–572 (1966).Google Scholar

Copyright information

© Springer-Verlag 1972

Authors and Affiliations

  • Heinz-Gerd Zimmer
    • 1
  • Gudrun Steinkopff
    • 1
  • Eckehart Gerlach
    • 1
  1. 1.Abteilung Physiologie, Medizinische FakultätTechnische Hochschule AachenAachenGermany

Personalised recommendations