Advertisement

Molecular and Cellular Biochemistry

, Volume 147, Issue 1–2, pp 105–114 | Cite as

Response of the rat heart to catecholamines and thyroid hormones

  • Heinz-Gerd Zimmer
  • Michael Irlbeck
  • Claudia Kolbeck-Rühmkorff
Part II: Myocytic Adaptation and Myocardial Injury

Abstract

Catecholamines and thyroid hormones have a similar influence on heart function and metabolism, but this may occur in a differential manner and to a different extent In this study, the effects of norepinephrine (NE) and of triiodothyronine (T3) were studied in regard to the function of the left (LV) and right ventricle (RV) and to the oxidative pentose phosphate pathway (PPP). NE was applied in rats as continuous i. v. infusion (0.2 mg/kg/h) for three days. T3 was given as daily s.c. injections (0.2 mg/kg) for the same period of time. LV, and RV function was measured in the closed-chest trapanal-anesthetized animals using special Millar ultraminature catheter pressure transducers. NE induced an increase in heart rate, in mean arterial pressure, and in total peripheral resistance (TPR). The cardiac RNA/DNA and the left ventricular weight/body weight ratios were increased by about 40%. These effects were prevented by simultaneous α-and β-receptor blockade with prazosin and metoprolol, respectively, but not by verapamil which abolished the hemodynamic effects. RVSP was significantly elevated by NE in a dose-dependent manner. The functional effects of T3 on the LV were not as pronounced as those induced by NE. Heart rate and LV dp/dtmax were increased by T3 and this increase was prevented by concomitant β-receptor blockade with, metoprolol. In contrast to NE, T3 induced an increase in cardiac output and a concominant decrease in TPR. The RNA/DNA ratio was elevated and cardiac hypertrophy had developed after treatment for three days with T3. These changes were not affected by β-receptor blockade with metoprolol. RVSP was increased by T3 to a lesser extent than with NE. In metabolic terms in turned out that only NE, but not T3 had a stimulating effect on the cardiac PPP. NE increased the mRNA and activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of this pathway. However, there was no effect of T3 on G-6-PD activity nor on 6-phosphogluconate dehydrogenase activity, one of the following enzymes in the pathway within the first 5 days of T3 treatment. These results demonstrate that the functional effects of T3 were not as pronounced as or even different from those of NE, and that T3 lacked a stimulating effect on the cardiac PPP.

Key words

pentose phosphate pathways heart function heart metabolism catecholamine effects thyroid hormone effects 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sutherland EW, Robison GA, Butcher RW: Some aspects of the biological role of adenosine 3′,5′-monophosphate (cyclic AMP). Circulation 37: 279–306, 1968Google Scholar
  2. 2.
    Tada M, Katz AM: Phosphorylation of the sarcoplasmatic reticulum and sarcolemma. Ann Rev Physiol 44: 401–423, 1982Google Scholar
  3. 3.
    Rupp H, Berger H-J, Pfeifer A, Werdan K: Effect of positive inotropic agents on myosin isozyme population and mechanical activity of cultured rat heart myocytes. Circ Res 68: 1164–1173, 1991PubMedGoogle Scholar
  4. 4.
    Zierhut W, Zimmer H-G: Significance of myocardial α- and β-adrenoceptors in catecholamine-induced cardiac hypertrophy. Circ Res 65: 1417–1425, 1989PubMedGoogle Scholar
  5. 5.
    Berridge MJ, Irvine RF: Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321, 1984PubMedGoogle Scholar
  6. 6.
    Nishizuka Y: The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334: 661–665, 1988PubMedGoogle Scholar
  7. 7.
    Schmitz W, Scholz H, Scholz J, Steinfath M: Increase in IP3 precedes α-adrenoceptor-induced increase in force of contraction in cardiac muscle. Eur J Pharmacol 140: 109–111, 1987PubMedGoogle Scholar
  8. 8.
    Kohl C, Schmitz W, Scholz H, Scholz J, Toth M, Döring V, Kalmar P: Evidence for α1-asrenoceptor-mediated increase of inositol trisphosphate in the human heart. J Cardiovasc Pharmacol 13: 324–327, 1989PubMedGoogle Scholar
  9. 9.
    Kolbeck-Rühmkorff C, Horban A, Zimmer H-G: Effect of pressure and volume overload on proto-oncogene expression in the isolated working rat heart. Cardiovasc Res 27: 1998–2004, 1993PubMedGoogle Scholar
  10. 10.
    Long CS, Ordahl CP, Simpson PC. α1-Adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. J Clin Invest 83: 1078–1082, 1989PubMedGoogle Scholar
  11. 11.
    Lee HR, Henderson SA, Reynolds R, Dunnmon P, Yuan D, Chien KR: α1-Adrenergic stimulation of cardiac gene transcription in neonatal rat myocardial cells. Effects on myosin light chain-2-gene expression. J Biol Chem 263: 7352–7358, 1988PubMedGoogle Scholar
  12. 12.
    Zimmer H-G, Lankat-Buttgereit B, Kolbeck-Rühmkorff C, Nagano T, Zierhut W: Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart. Circ Res 71: 451–459, 1992PubMedGoogle Scholar
  13. 13.
    Oppenheimer JH: Thyroid hormone action at the cellular level. Science 203: 971–979, 1979PubMedGoogle Scholar
  14. 14.
    Weinberger C, Thompson CC, Ong ES, Lebo R, Gruol DJ, Evans RM: The c-erb-A gene encodes a thyroid hormone receptor. Nature 324: 641–646, 1986PubMedGoogle Scholar
  15. 15.
    Martial JA, Baxter JD, Goodman HM, Seeburg PH: Regulation of growth hormone messenger RNA by thyroid and glucocorticoid hormones. Proc Natl Acad Sci USA 74: 1816–1820, 1977PubMedGoogle Scholar
  16. 16.
    Williams LT, Lefkowitz, RJ, Watanabe AM, Hathaway DR, Besch HR: Thyroid hormone regulation of β-adrenergic receptor number. J Biol Chem 252: 2787–2789, 1977PubMedGoogle Scholar
  17. 17.
    Ismail-Beigi F, Bissell DM, Edelman IS: Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture. Direct action of thyroid hormonein vitro. J Gen Physiol 73: 369–383, 1979PubMedGoogle Scholar
  18. 18.
    Bartolome J, Huguenard J, Slotkin TA: Role of ornithine decarboxylase in cardiac growth and hypertrophy. Science 210: 793–794, 1980PubMedGoogle Scholar
  19. 19.
    Pegg AE, Hibasami H: Polyamine metabolism during cardiac hypertrophy. Am J Physiol 239: E372-E378, 1980PubMedGoogle Scholar
  20. 20.
    Schimmelpfennig K, Sauerberg M, Neubert D: Stimulation of mitochondrial RNA synthesis by thyroid hormone. FEBS Letters 10: 269–272, 1970PubMedGoogle Scholar
  21. 21.
    Nelson BD, Joste V, Wielburski A, Rosenqvist U The effects of triiodothyronine on the synthesis of mitochondrial proteins in isolated rat hepatocytes. Biochim Biophys Acta 608: 422–426, 1980PubMedGoogle Scholar
  22. 22.
    Seymour A-ML, Eldar H, Radda GK: Hyperthyroidism results in increased glycolytic capacity in the rat heart. A31P-NMR study. Biochim Biophys Acta 1055: 107–116, 1990PubMedGoogle Scholar
  23. 23.
    Tanaka T, Morita H, Koide H, Kawamura K, Takatsu T: Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat. Basic Res Cardiol 80: 165–174, 1985Google Scholar
  24. 24.
    Hoh JFY, McGrath PA, Hale PT: Electrophoretic analysis of multiple forms of rat cardiac myosin: effects of hypophysectomy and thyroid replacement. J Mol Cell Cardiol 10: 1053–1076, 1977Google Scholar
  25. 25.
    Hoh JFY, Egerton LJ: Action of triiodothyronine on the synthesis of rat ventricular myosin isoenzymes. FEBS Letters 101: 143–148, 1979PubMedGoogle Scholar
  26. 26.
    Chizzonite RA, Zak R: Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones. J Biol Chem 259: 12628–12632, 1984PubMedGoogle Scholar
  27. 27.
    Gustafson TA, Markham BE, Morkin E: Effects of thyroid hormone on α-actin and myosin heavy chain gene expression in cardiac and skeletal muscle of the rat: measurement of mRNA content using synthetic oligonucleotide probes. Circ Res 59: 194–201, 1986PubMedGoogle Scholar
  28. 28.
    Zimmer H-G: Measurement of left ventricular hemodynamic parameters in closed-chest rats under control and various pathophysiological conditions. Basic Res Cardiol 78: 77–84, 1983PubMedGoogle Scholar
  29. 29.
    Zimmer H-G, Zierhut W, Seesko RC, Varekamp AE: Right heart catheterization in rats with pulmonary hypertension and right ventricular hypertrophy. Basic Res Cardiol 83: 48–57, 1988PubMedGoogle Scholar
  30. 30.
    Zimmer H-G: The oxidative pentose phosphate pathway in the heart: Regulation, physiological significance, and clinical implications. Basic Res Cardiol 87: 303–316, 1992Google Scholar
  31. 31.
    Zimmer H-G, Ibel H: Effects of ribose on cardiac metabolism and function in isoproterenol-treated rats. Am J Physiol 245: H880-H886, 1983PubMedGoogle Scholar
  32. 32.
    Zimmer H-G, Ibel H, Steinkopff G, Korb G: Reduction of the isoproterenol-induced alterations in cardiac adenine nucleotides and morphology by ribose. Science 207: 319–321, 1980PubMedGoogle Scholar
  33. 33.
    Zimmer H-G, Ibel H: Ribose accelerates the repletion of the ATP pool during recovery from reversible ischemia of the rat myocardium. J Mol Cell Cardiol 16: 863–866, 1984PubMedGoogle Scholar
  34. 34.
    Zimmer H-G: Normalization of depressed heart function in rats by ribose. Science 220: 81–82, 1983PubMedGoogle Scholar
  35. 35.
    Zimmer H-G, Martius PA, Marschner G Myocardial infarction in rats: effects of metabolic and pharmacologic interventions. Basic Res Cardiol 84: 332–343, 1989PubMedGoogle Scholar
  36. 36.
    Zimmer H-G, Ibel H, Suchner U: β-Adrenergic agonists stimulate the oxidative pentose phosphate pathway in the rat heart. Circ Res 67: 1525–1534, 1990PubMedGoogle Scholar
  37. 37.
    Glock GE, McLean P: Further studies on the properties and assay of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. Biochem J 55: 400–408, 1953PubMedGoogle Scholar
  38. 38.
    Glock GE, McLean P: Levels of enzymes of the direct oxidative pathway of carbohydrate metabolism in mammalian tissues and tumours. Biochem J 56: 171–175, 1954PubMedGoogle Scholar
  39. 39.
    Robinson HW, Hodgen CG: The biuret reaction in the determination of serum proteins. J Biol Chem 135: 727–731, 1940Google Scholar
  40. 40.
    Birnboim HC: Rapid extraction of high molecular weight RNA from cultured cells and granulocytes for Northern analysis. Nucleic Acids Res 16: 1487–1497, 1988PubMedGoogle Scholar
  41. 41.
    Maniatis T, Fritsch EF, Sambrook J: Molecular Cloning. Cold Spring Harbor, NY. Cold Spring Harbor Laboratory, 1982Google Scholar
  42. 42.
    Wallenstein S, Zucker CL, Fleiss JL: Some statistical methods useful in circulation research. Circ Res 47: 1–9, 1980PubMedGoogle Scholar
  43. 43.
    Zierhut W, Zimmer H-G: Differential effects of triiodothyronine on rat left and right ventricular function and the influence of metoprolol. J Mol Cell Cardiol 21: 617–624, 1989PubMedGoogle Scholar
  44. 44.
    Rona G, Chappell CI, Kahn DS: The significance of factors modifying the development of isoproterenol-induced myocardial necrosis. Am Heart J 66: 389–395, 1963PubMedGoogle Scholar
  45. 45.
    Gerdes AM, Moore JA, Bishop SP: Failure of propranolol to prevent chronic hyperthyroid induces hypertrophy and multifocal cellular necrosis in the rat. Can J Cardiol 1: 340–345, 1985PubMedGoogle Scholar
  46. 46.
    Van Liere EJ, Sizemore DA, Hunnel J.: Size of cardiac ventricles in experimental hyperthyroidism in the rat. Proc Soc Exp Biol Med 132: 663–665, 1969PubMedGoogle Scholar
  47. 47.
    Gerdes AM, Moore JA, Hines JM: Regional changes in myocyte size and number in propranolol-treated hyperthyroid rats. Lab Invest 57: 708–713, 1987PubMedGoogle Scholar
  48. 48.
    Zimmer H-G, Ibel H, Gerlach E: Significance of the hexose monophosphate shunt in experimentally induced cardiac hypertrophy. Basic Res Cardiol 75: 207–213, 1980PubMedGoogle Scholar
  49. 49.
    Zimmer H-G, Peffer H: Metabolic aspects of the development of experimental cardiac hypertrophy. Basic Res Cardiol 81 (Suppl 1): 127–137, 1986PubMedGoogle Scholar
  50. 50.
    Heckmann M, Zimmer H-G: Effects of triiodothyronine in spontaneously hypertensive rats. Studies on cardiac metabolism, function and heart weight. Basic Res Cardiol 87: 333–343, 1992PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Heinz-Gerd Zimmer
    • 1
  • Michael Irlbeck
    • 1
  • Claudia Kolbeck-Rühmkorff
    • 1
  1. 1.Department of PhysiologyUniversity of MunichGermany

Personalised recommendations