Chronic cardiac reactions. IV. Effect of drugs and altered functional loads on cardiac energetics as inferred from myofibrillar ATPase and the myosin isoenzyme population

  • Heinz Rupp
  • R. Wahl
  • R. Jacob
Conference paper


A major determinant of myocardial energetics is the ATPase activity of myofibrils. In order to account for chronic changes in myofibrillar ATPase, the state equation of the intertropomyosin-interaction model of Tawada et al. [35] was extended by introducing the rates of cross-bridge cycling of myofibrils composed of V-1 or V-3 and the concentration of the myosin isoenzymes. Cross-bridge cycling rates of 1.0 or 0.7 were derived for myofibrils composed of V-1 or V-3, respectively. Ca2+ responsiveness and positive co-operativity were not significantly affected by the myosin isoenzymes. Redistribution of the myosin isoenzyme population and thus altered myocardial energetics was observed following administration of various drugs and as a result of different functional loads. Besides thyroid hormones, catecholamines had a marked influence on myosin. Reducing the adrenergic drive by administration of atenolol, guanethidine or reserpine led to a shift in the direction of V-3. Since serum T3 levels were not significantly reduced by these interventions, the drugs act most probably at the organ level. The functional states responsible for the increase in the proportion of V-3 (pressure load, intermittent feeding, schedule-induced stress) also did not affect circulating T3 in a manner that could entirely explain the redistribution. Hypertrophy-induced dilution of sympathetic nerve fibres or reduced adrenergic responsiveness most likely play a role in the redistribution. An increase in the proportion of V-1 was observed following swimming exercise but not, however, after spontaneous or enforced running. In the swim-exercised rats, T3 was markedly reduced. Thus, the trigger reactions linked most probably to the high adrenergic drive during swimming have to overcome the lower T3 level. It is concluded that myocardial energetics can be decisively altered by a variety of drugs and functional loads, whereby the trigger reactions leading to an altered gene expression of myosin cannot be accounted for entirely by altered circulating T3 but most probably involve the adrenergic system.


Thyroid Hormone ATPase Activity Swimming Exercise Trigger Reaction Myofibrillar ATPase 
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  1. 1.
    Alpert NR, Mulieri LA (1986) Intrinsic determinants of myocardial energetics in normal and hypertrophied hearts. In: Rupp H (ed) Regulation of heart function — basic concepts and clinical applications. Thieme, Stuttgart New York, pp 292–304Google Scholar
  2. 2.
    Chizzonite RA, Zak R (1984) Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones. J Biol Chem 259: 12628–12632PubMedGoogle Scholar
  3. 3.
    Dillmann WH (1985) Methyl palmoxirate increases Cat+-myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart. Am J Physiol 248: E602 — E606PubMedGoogle Scholar
  4. 4.
    Dillmann WH, Barrieux A, Reese GS (1984) Effect of diabetes and hypothyroidism on the predominance of cardiac myosin heavy chains synthesized in vivo or in a cell-free system. J Biol Chem 259: 2035–2038PubMedGoogle Scholar
  5. 5.
    Dillmann WH, Berry S, Alexander NM (1983) A physiological dose of triiodothyronine normalizes cardiac myosin adenosine triphosphatase activity and changes myosin isoenzyme distribution in semistarved rats. Endocrinology 112: 2081–2087PubMedCrossRefGoogle Scholar
  6. 6.
    Falk JL, Tang M, Forman S (1977) Schedule-induced chronic hypertension. Psychosom Med 39: 252–263Google Scholar
  7. 7.
    Franks K, Cooke R, Stull JT (1984) Myosin phosphorylation decreases the ATPase activity of cardiac myofibrils. J Mol Cell Cardiol 16: 597–604PubMedCrossRefGoogle Scholar
  8. 8.
    Heyliger CE, Pierce GN, Singal PK, Beamish RE, Dhalla NS (1982) Cardiac alpha-and betaadrenergic receptor alterations in diabetic cardiomyopathy. Basic Res Cardiol 77: 610–618PubMedCrossRefGoogle Scholar
  9. 9.
    Horowitz M, Peyser YM, Muhlrad A (1986) Alterations in cardiac myosin isoenzymes distribution as an adaptation to chronic environmental heat stress in the rat. J Mol Cell Cardiol 18: 511515Google Scholar
  10. 10.
    Jacob R, Vogt M, Rupp H (1987) Physiological and pathological hypertrophy. In: Dhalla NS, Singal PK, Beamish RE (eds) Pathophysiology of heart disease. Martinus Nijhoff Publishing Boston (in press)Google Scholar
  11. 11.
    Kissling G, Rupp H, Malloy L, Jacob R (1982) Alterations in cardiac oxygen consumption under chronic pressure overload. Significance of the isoenzyme pattern of myosin. Basic Res Cardiol 77: 255–269Google Scholar
  12. 12.
    Lompré AM, Nadal-Ginard B, Mandavi V (1984) Expression of the cardiac ventricular alpha-and beta-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem 259: 6437–6443PubMedGoogle Scholar
  13. 13.
    Mandavi V, Strehler EE, Periasamy M, Wieczorek DF, Izumo S, Nadal-Ginard B (1986) Sarcomeric myosin heavy chain gene family: organization and pattern of expression. Med Sci Sports Exerc 18: 299–308CrossRefGoogle Scholar
  14. 14.
    Martin AF, Robinson DC, Dowell RT (1985) Isomyosin and thyroid hormone levels in pressure overload weanling and adult rat hearts. Am J Physiol 248: H305 — H310PubMedGoogle Scholar
  15. 15.
    Morano I, Hofmann F, Zimmer M, Rüegg JC (1985) The influence of P-light chain phosphorylation by myosin light chain kinase on the calcium sensitivity of chemically skinned heart fibres. FEBS Lett 189: 221–224PubMedCrossRefGoogle Scholar
  16. 16.
    Pagani ED, Solaro RJ (1983) Swimming exercise, thyroid state and the distribution of myosin isoenzymes in rat heart. Am J Physiol 245: 713–720Google Scholar
  17. 17.
    Pauletto P, Dalla Libera L, Vescovo G, Scannapieco G, Angelini A, Pessina AC, Dal Palu C (1985) Propranolol-induced changes in ventricular isomyosin composition in the rat. Am Heart J 109: 1269–1273PubMedCrossRefGoogle Scholar
  18. 18.
    Rupp H (1982) Polymorphic myosin as the common determinant of myofibrillar ATPase in different haemodynamic and thyroid states. Basic Res Cardiol 77: 34–46PubMedCrossRefGoogle Scholar
  19. 19.
    Rupp H (1983) The determinants of the calcium-dependent activation of myofibrils from rat heart as judged by myofibrillar adenosine triphosphatase and superprecipitation of natural actomyosin. Mol Physiol 3: 249–263Google Scholar
  20. 20.
    Rupp H (1985) Association of ventricular myosin heavy chains in functional states which lead to isoenzyme populations encompassing the whole range of possible distribution. Basic Res Cardiol 80: 608–616PubMedCrossRefGoogle Scholar
  21. 21.
    Rupp H, Bukhari AR, Jacob R (1983) Regulation of cardiac myosin isoenzymes — The interrelationship with catecholamine metabolism. J Mol Cell Cardiol [Suppl 1] 15: 317Google Scholar
  22. 22.
    Rupp H, Felbier H-R, Bukhari AR, Jacob R (1984) Modulation of myosin isoenzyme populations and activities of monoamine oxidase and phenylethanolamine-N-methyltransferase in pressure loaded and normal rat heart by swimming exercise and stress arising from electrostimulation in pairs. Can J Physiol Pharmacol 62: 1209–1218PubMedCrossRefGoogle Scholar
  23. 23.
    Rupp H, Jacob R (1982) Response of blood pressure and cardiac myosin polymorphism to swimming training in the spontaneously hypertensive rat. Can J Physiol Pharmacol 60: 10981103Google Scholar
  24. 24.
    Rupp H, Jacob R (1983) The interrelationship between normalization of pressure load of heart and hypertrophy and myosin isoenzyme population in the SHR. J Mol Cell Cardiol [Suppl 2] 15: 63CrossRefGoogle Scholar
  25. 25.
    Rupp H, Jacob R (1986) Correlation between total catecholamine content and redistribution of myosin isoenzymes in pressure loaded ventricular myocardium of the spontaneously hypertensive rat. Basic Res Cardiol [Suppl 1] 81: 147–155Google Scholar
  26. 26.
    Rupp H, Jacob R (1986) Myocardial transitions between fast-and slow-type muscle as monitored by the population of myosin isoenzymes. In: Rupp H (ed) Regulation of heart function — basic concepts and clinical applications. Thieme, Stuttgart New York, pp 271–291Google Scholar
  27. 27.
    Rupp H, Popova N, Jacob R (1983) In: Jacob R, Gülch R, Kissling G (eds) Cardiac adaptation to hemodynamic overload, training and stress. Steinkopff Verlag, Darmstadt, pp 46–52Google Scholar
  28. 28.
    Rupp H, Wahl R, Jacob R (1987) Remodelling of the myocyte at a molecular level — Relationship between myosin isoenzyme population and sarcoplasmic reticulum. In: Dhalla NS, Pierce GN, Beamish RE (eds) Heart function and metabolism. Martinus Nijhoff Publishing, Boston (in press)Google Scholar
  29. 29.
    Samuel J-L, Rappaport L, Mercadier J-J, Lompré A-M, Sartore S, Triban C, Schiaffino S, Schwartz K (1983) Distribution of myosin isozymes within single cardiac cells. An immunohistochemical study. Circ Res 52: 200–209Google Scholar
  30. 30.
    Samuel J-L, Rappaport L, Syrovy I, Wisnewsky C, Marotte F, Whalen RG, Schwartz K (1986) Differential effect of thyroxine on atrial and ventricular isomyosins in rats. Am J Physiol 250: H333 — H341PubMedGoogle Scholar
  31. 31.
    Schaible TF, Malhotra A, Ciambrone GJ, Scheuer J (1986) Chronic swimming reverses cardiac dysfunction and myosin abnormalities in hypertensive rats. J Appl Physiol 60: 1435–1441PubMedGoogle Scholar
  32. 32.
    Sheer D, Morkin E (1984) Myosin isoenzyme expression in rat ventricle: effects of thyroid hormone analogs, catecholamines, glucocorticoids and high carbohydrate diet. J Pharmacol Exp Ther 229: 872–879PubMedGoogle Scholar
  33. 33.
    Sreter FA, Faris R, Balogh I, Somogyi E, Sotonyi P (1982) Changes in myosin isozyme distribution induced by low doses of isoproterenol. Arch Int Pharmacodyn Ther 260: 159–164PubMedGoogle Scholar
  34. 34.
    Sweeney HL, Stull JT (1986) Phosphorylation of myosin in permeabilized mammalian cardiac and skeletal muscle cells. Am J Physiol 250: C657 — C660PubMedGoogle Scholar
  35. 35.
    Tawada Y, Ohara H, Ooi T, Tawada K (1975) Non-polymerizable tropomyosin and control of the superprecipitation of actomyosin. J Biochem 78: 65–72PubMedGoogle Scholar
  36. 36.
    Wiegand V, Henniges H, Oberschmidt R, Kreuzer H (1985) Influence of the thyroid state on myocardial myosin in the adult pig heart. Basic Res Cardiol 80: 12–17PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Heinz Rupp
    • 1
    • 3
  • R. Wahl
    • 2
  • R. Jacob
    • 3
  1. 1.Physiologisches Institut IITübingenGermany
  2. 2.Medizinische Klinik (IV)Universität TübingenGermany
  3. 3.Physiologisches Institut (II)Universität TübingenGermany

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