Molecular and Cellular Biochemistry

, Volume 107, Issue 2, pp 169–183 | Cite as

Alterations in cardiac function and subcellular membrane activities after hypervitaminosis D3

  • Satoshi Takeo
  • Reiko Tanonaka
  • Kouichi Tanonaka
  • Keiko Miyake
  • Hideto Hisayama
  • Norifumi Ueda
  • Keiko Kawakami
  • Hiromi Tsumura
  • Shuichi Katsushika
  • Yuzo Taniguchi
Article

Abstract

The present study was designed to induce massive accumulation of calcium in the myocardium and to evaluate the effect of calcium overload on myocardial contractile function and biochemical activity of cardiac subcellular membranes. Rats were treated with an oral administration of 500,000 units/kg of vitamin D3 for 3 consecutive days, and their hearts were sampled on the 5th day for biochemical analysis. On the 4th and 5th days, heart rate, mean aortic pressure, left ventricular systolic pressure and left ventricular dP/dt were significantly lowered in vitamin D3-treated rats, demonstrating the existence of appreciable myocardial contractile dysfunction. Marked increases in the myocardial calcium (67-fold increase) and mitochondrial calcium contents (24-fold increase) were observed by hypervitaminosis D3. Mitochondrial oxidative phosphorylation and ATPase activity were significantly reduced by this treatment. A decline in sarcolemmal Na+, K+-ATPase activity was also observed, while relatively minor or insignificant changes in calcium uptake and ATPase activities of sarcoplasmic reticulum were detectable. Electron microscopic examination revealed calcium deposits in the mitochondria after vitamin D3 treatment. The results suggest that hypervitaminosis D3 produces massive accumulation of calcium in the myocardium, particularly in the cardiac mitochondrial membrane, which may induce an impairment in the mitochondrial function and eventually may lead to a failure in the cardiac contractile function.

Key words

calcium accumulation calcium uptake Ca2−, Mg2+-ATPase contractile function vitamin 133 myocardium mitochondria sarcolemma sarcoplasmic reticulum Na+, K+-ATPase 

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References

  1. 1.
    Bonucci E, Sadun R: Experimental calcification of the myocardium. Am J Pathol 71: 167–192, 1973Google Scholar
  2. 2.
    Hass GM, Trueheart RE, Taylor CB, Stumpe M: An experimental histologic study of hypervitaminosis D. Am J Pathol 34: 395–431, 1958Google Scholar
  3. 3.
    Kent SP, Vawter GF, Dowben RM, Benson RE: Hypervitaminosis D in monkeys: a clinical and pathologic study. Am J Pathol 34: 37–59,1958Google Scholar
  4. 4.
    McClure J, Piterse AS, Pounder DJ, Smith PS: Myocardial fiber calcification. J Clin Pathol 134: 13–25, 1981Google Scholar
  5. 5.
    Selye H, Yeghiayan E, Mandeville R: Protection by catatoxic steroids aganist dihydrotachysterol intoxication. Atherosclerosis 11: 321–331, 1970Google Scholar
  6. 6.
    Takeo S, Anan M, Fujioka K, Kajihara T, Hiraga K, Miyake K, Tanoanka K, Minematsu R, Mori H, Taniguchi K: Functional changes of aorta with massive accumulation of calcium. Atherosclerosis 77: 175–181, 1989Google Scholar
  7. 7.
    Lowry OH, Rosebrough NJ, Farr AL, Randal RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275,1951PubMedGoogle Scholar
  8. 8.
    Takeo S, Sakanashi M: Possible mechanisms for reoxygenation-induced recovery of myocardial high-energy phosphates after hypoxia. J Mol Cell Cardiol 15: 577–594, 1983Google Scholar
  9. 9.
    Sordahl LA, Johnson LA, Balilock ZR, Schwartz A: The mitochondrion. In: A Schwartz (ed) Methods in Pharmacology vol 1, Appelton-Century-Crofts, New York, 1974, p.247–286Google Scholar
  10. 10.
    Takeo S, Taam GML, Beamish RE, Dhalla NS: Effect of adrenochrome on calcium accumulation by heart mitochondria. Biochem Pharmacol 30: 157–163, 1980Google Scholar
  11. 11.
    Takeo S, Taam GML, Beamish RE, Dhalla NS: Effects of adrenochrome on calcium accumulating and adenosine triphosphatase activities of the rat heart microsomes. J Pharmacol Exp Ther 242: 688–693, 1980Google Scholar
  12. 12.
    Takeo S, Adachi M, Sakanashi M: A possible action of nicardipine on the cardiac sarcolemmal Na+-Ca2+ exchange. Biochem Pharmacol 34: 2303–2308, 1985Google Scholar
  13. 13.
    Wharton DC, Tzagoloff A: Cytochrome c oxidase from beef heart mitochondria. In: RW Estabrook and ME Pullman (eds) Methods in Enzymology vol 10, Academic Press, New York, 1967, p. 245–250Google Scholar
  14. 14.
    Phillips AH, Langdon RG: Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J Biol Chem 237: 2652–2660,1962Google Scholar
  15. 15.
    Martin AF, Panagi AF, Solaro RJ: Thyroxine-induced redistribution of isoenzymes of rabbit ventricular myosin. Circ Res 50: 117–124, 1982Google Scholar
  16. 16.
    Karnovsky MJ: A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol 27: 137A, 1965Google Scholar
  17. 17.
    Millonig G: Advantages of a phosphate buffer for OsO4 solution in fixation. J Appl Physiol 32: 1637, 1961Google Scholar
  18. 18.
    Luft JH: Improvement in epoxy resin embedding methods. J Biochem Cytol 9: 409–414, 1961Google Scholar
  19. 19.
    Whatson ML: Staining of tissue section for electron microscopy with heavy metals. J Biophy Biochem Cytol 4: 475–485,1958Google Scholar
  20. 20.
    Reynolds ES: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212,1963CrossRefPubMedGoogle Scholar
  21. 21.
    Fleckenstein A: Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the production or prevention of myocardial lesions. In: P Harris and LH Opie (eds) Calcium and the Heart, Academic Press, London, 1971, p. 135–188Google Scholar
  22. 22.
    Katz AM: Structure and function of cardiac muscle. In: AM Katz (ed) Physiology of the Heart, Raven Press, New York, 1977, p. 1–24Google Scholar
  23. 23.
    Carafoli E: Intracellular calcium homeostasis. Ann Rev Biochem 56: 396–434, 1987Google Scholar
  24. 24.
    Thiers RE, Reynolds ES, Vallee BL: The effect of carbon tetrachloride poisoning on subcellular metal distribution in rat liver. J Biol Chem 235: 2130–2133, 1960Google Scholar
  25. 25.
    Carafoli E, Tiozzo R, Pasquali-Ronchetti I, Laschi R: A study of Ca2+ metabolism in kidney mitochondria during acute uranium intoxication. Lab Invest 25: 516–527, 1971Google Scholar
  26. 26.
    Suko J, Vogel JHK, Chidsey CA: Reduced calcium uptake and ATPase of the sarcoplasmic reticular fraction prepared from chronically failing calf hearts. Ore Res 27: 235–247, 1970Google Scholar
  27. 27.
    Sulakhe PV, Dhalla NS: Excitation-contraction coupling in heart. VII. Calcium accumulation in subcellular particles in congestive heart failure. J Clin Invest 50: 1019–1027, 1971Google Scholar
  28. 28.
    Yazaki Y, Fujii J: Depressed Na, K-ATPase activity in the failing rabbit heart. Jpn Heart J 13: 73–83, 1972Google Scholar
  29. 29.
    Tomlinson CW, Lee SL, Dhalla NS: Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit. Circ Res 39: 82–92, 1976Google Scholar
  30. 30.
    Beller GA, Conroy J, Smith T: Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding. J Clin Invest 57: 341–350, 1976Google Scholar
  31. 31.
    Dhalla NS, Singh JN, Bajusz E, Jasmin G: Comparison of heart sarcolemmal enzyme activities in normal and cardiomyopathic (UM-X7.1) hamsters. Clin Sci Mol Med 51: 233–242,1976Google Scholar
  32. 32.
    Fedelesova M, Sulakhe PV, Yates JC, Dhalla NS: Biochemical basis of heart function IV. Energy metabolism and calcium transport in hearts of vitamin E deficient rats. Can J Physiol Pharmacol 49: 909–918, 1971Google Scholar
  33. 33.
    Lamers JM, Stinis JT, Ruigrok TJ: Biochemical properties of membrane isolated from calcium-depleted rabbit hearts. Circ Res 54: 217–226, 1984Google Scholar
  34. 34.
    Alto LH, Dhalla NS: Role of changes in microsomal calcium uptake in the effects of reperfusion of Ca2+ -deprived hearts. Circ Res 48: 17–24, 1981Google Scholar
  35. 35.
    Kai-Yamamoto M, Kanaide H, Meno H, Yamamoto H, Nakamura M: Changes in subcellular calcium transport in rat hearts during the calcium paradox. Br J Exp Pathol 66: 623–631,1985Google Scholar
  36. 36.
    Alto LH, Dhalla NS: Myocardial cation contents during induction of calcium paradox. Am J Physiol 237: H713-H719, 1979Google Scholar
  37. 37.
    Nayler WG, Elz JS, Perry SE, Daly MJ: The biochemistry of uncontrolled calcium entry. Eur Heart J 4(Suppl. H): 29–41,1983Google Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Satoshi Takeo
    • 1
  • Reiko Tanonaka
    • 1
  • Kouichi Tanonaka
    • 1
  • Keiko Miyake
    • 1
  • Hideto Hisayama
    • 2
  • Norifumi Ueda
    • 2
  • Keiko Kawakami
    • 2
  • Hiromi Tsumura
    • 1
  • Shuichi Katsushika
    • 3
  • Yuzo Taniguchi
    • 4
  1. 1.Department of PharmacologyTokyo College of PharmacyHorinouchi, Hachioji, TokyoJapan
  2. 2.Department of Pharmacology, Faculty of Pharmaceutical SciencesFukuyama UniversityJapan
  3. 3.Department of Internal Medicine, National Defense Medical CollegeJapan
  4. 4.Institute of Environmental Health and BiologyJapan

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