Advertisement

Basic Research in Cardiology

, Volume 92, Issue 1, pp 1–7 | Cite as

Decrease in myocardial Na+-K+-ATPase activity and ouabain binding sites in hypercholesterolemic rabbits

  • W. -J. Chen
  • S. -Y. Lin-Shiau
  • H. -C. Huang
  • Y. -T. Lee
Original Contribution

Abstract

Objectives

The purpose of this study was to explore the effect of high dietary cholesterol on the lipid composition, Na+−K+-ATPase activity and ouabain receptor property of the myocardial sarcolemma.

Methods

Male New Zealand white rabbits were fed with standard chow or standard chow supplemented with 0.5% (w/w) cholesterol and 10% (w/w) coconut oil to induce hypercholesterolemia. After 8 weeks, the rabbits were sacrificed; a myocardial sarcolemma fraction was then prepared from the left ventricular myocardium and analyzed for lipid composition. Assay of Na+−K+-ATPase activity and3H-ouabain binding studies were performed in the myocardial sarcolemma from the control and cholesterol-fed rabbits.

Results

The cholesterol content, but not the phospholipid content, of the sarcolemma was significantly greater in the cholesterol-fed group, thus, resulting in an increased cholesterol/phospholipid molar ratio in the cholesterol-fed group. In addition, a decrease in Na+−K+-ATPase activity was also found in this group. The decrease in Na+−K+-ATPase activity was selective, since the Mg++-ATPase and 5′-nucleotidase activities remained unchanged. In the3H-ouabain binding study, a decrease in the number of maximum binding sites, but not the binding affinity, for3H-ouabain was foundie the cholesterol-fed group.

Conclusions

High dietary cholesterol induces higher levels of cholesterol not only in the plasma, but also in the myocardial sarcolemma. These changes result in decreased myocardial Na+−K+-ATPase activity mediated by a reduction in the maximum number of binding sites for ouabain but not a change in binding affinity.

Key words

Hypercholesterolemia membrane lipid Na+−K+-ATPase ouabain receptor 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Abeywardena MY, McMurchie EJ, Russell GR, Sayer WH, Charnock JS (1984) Response of rat heart membrane and associated ion-transporting ATPase to dietary lipid. Biochim Biophys Acta 776: 48–59Google Scholar
  2. 2.
    Akera T, Brody TM (1978) The role of Na+−K+ ATPase in the inotropic action of digitalis. Pharmacol Rev 29: 187–220Google Scholar
  3. 3.
    Alam SQ, Ren YF, Alam BS (1989) Effect of dietary trans fatty acids on some membrane-associated enzymes and receptors in rat heart. Lipids 24: 39–44Google Scholar
  4. 4.
    Chen CC, Lin-Shiau SY (1985) Mode of inhibitory action of melittin on Na+−K+-ATPase activity of the rat synaptic membrane. Biochem Pharmacol 34: 2335–41Google Scholar
  5. 5.
    Chen CC, Lin-Shiau SY (1986) Decreased Na+−K+ ATPase activity and3[H]-ouabain binding sites in various tissue of spontaneously hypertensive rats. Eur J Pharmacol 122: 311–9Google Scholar
  6. 6.
    Chen CC, Lin-Shiau SY (1988) ATPase activities in the kidney and heart of alloxan-induced diabetic mice. Asia Pacific J Pharmacol 3: 51–55Google Scholar
  7. 7.
    Chen CC, Lin-Shiau SY (1989) Myocardial Na+−K+ ATPase activity and3[H]-ouabain binding sites in hypertensive rats. Eur J Pharmacol 169: 67–74Google Scholar
  8. 8.
    Corvera E, Mouritsen OG, Singer MA, Zuckermann MJ (1992) The permeability and the effect of acyl-chain length for phospholipid bilavers containing cholesterol: theory and experiment. Biochim Biophys Acta 1107: 261–70Google Scholar
  9. 9.
    Field FJ, Albright E, Mathur SN (1986) Effects of dietary cholesterol on biliary cholesterol content and bile flow. Gastroenterology 91: 297–304Google Scholar
  10. 10.
    Gokkusu C, Oz H (1990) Influence of thymic fraction 5 on erythrocyte (Na+−K+)-ATPase activity in hypercholes-terolemic rabbit. Internatl J Vit Nutr Res 60: 398–401Google Scholar
  11. 11.
    Hansen O, Clausen T (1988) Quantitative determination of Na+−K+-ATPase and other sarcolemmal components in muscle cells. Am J Physiol 254: C1-C7Google Scholar
  12. 12.
    Ho KJ, Pang LC, Taylor CB (1974) Modes of cholesterol accumulation in various tissue of rabbits with prolonged exposure to various serum cholesterol levels. Atherosclerosis 19: 561–6Google Scholar
  13. 13.
    Jones LR, Besch HR Jr (1984) Isclation of canine cardiac sarcolemmal vesicles. Method Pharmacol 5: 1–12Google Scholar
  14. 14.
    Kimelberg HK, Papahadjopoulos D (1974) Effects of phospholipid acyl chain fluidity, phase transitions, and cholesterol on (Na+−K+)-stimulated adenosine triphosphatase. J Biol Chem 249: 1071–80Google Scholar
  15. 15.
    Kjeldsen K, Everts ME, Clausen T (1986) Effects of semi-starvation and potassium deficiency on the concentration of [3H]ouabain-binding sites and sodium and potassium contents in rat skeletal muscle. Br J Nutrit 56: 519–32Google Scholar
  16. 16.
    Kutryk MJB, Pierce GN (1988) Stimulation of sodium-calcium exchange by cholesterol incorporation into isolated cardiac sarcolemmal vesicles. J Biol Chem 263: 13167–72Google Scholar
  17. 17.
    Lars Bastiaanse EM, Atsma DE, Kuijpers MMC, Van der Laarse A (1994) The effect of sarcolemmal content on intracellular calcium ion concentration in cultured cardiomyocytes. Arch Biochem Biophys 313: 58–63Google Scholar
  18. 18.
    Lin-Shiau SY, Chen CC (1982) Effects of β-bungarotoxin and phospholipase A2 fromNaja naja atra snake venom on ATPase activities of synaptic membrane from rat cerebral cortex. Toxicon 20: 409–17Google Scholar
  19. 19.
    Liu K, Pierce GN (1993) The effects of low density lipoprotein on calcium transients in isolated rabbit cardiomyocytes. J Biol Chem 268: 3767–75Google Scholar
  20. 20.
    Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin-phenol reagent. J Biol Chem 193: 265–275Google Scholar
  21. 21.
    Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D (1986) Serum cholesterol, blood pressure and mortality: Implications from a cohort of 361,662 men. Lancet 2: 933–36Google Scholar
  22. 22.
    Mason RP, Moisey DM, Shajenko L (1992) Cholesterol alters the binding of Ca2+ channel blockers to the membrane lipid bilayer. Mol Pharmacol 41: 315–21Google Scholar
  23. 23.
    McMurchie EJ, Patten GS (1988) Dietary cholesterol influences cardiac β-adrenergic receptor adenylate cyclase activity in the marmoset monkey by changes in membrane cholesterol status. Biochim Biophys Acta 942: 324–32Google Scholar
  24. 24.
    Norgaard A, Baandrup U, Larsen JS, Kjeldsen K (1987) Heart Na, K-ATPase activity in cardiomyopathic hamsters as estimated from K-dependent 3-O-MFPase activity in crude homogenate. J Mol Cell Cardiol 19: 589–94Google Scholar
  25. 25.
    Norgaard A, Bagger JP, Bjerregaard P, Baandrup U, Kzeldsen K, Thomsen PEB (1988) Relation of left ventricular function and Na−K pump concentration in suspected idiopathic dilated cardiomyopathy. Am J Cardiol 61: 1312–15Google Scholar
  26. 26.
    Norgaard A, Kjeldsen K, Hansen O (1985) K+-dependent 3-O-methyl-fluorescein phosphatase activity in crude homogenate of rodent heart ventricle: effect of K+ depletion and changes in thyroid status. Eur J Pharmacol 113: 373–82Google Scholar
  27. 27.
    Okumura T, Kadono T, Iso'o A (1975) Sintered thin-layer chromatography with flame ionization detector scanning. J Chromatogr 108: 329–36Google Scholar
  28. 28.
    Ortega A, Mas-Oliva J (1984) Cholesterol effect on enzyme activity of the sarcolemmal (Ca2++Mg2+)-ATPase from cardiac muscle. Biochim Biophys Acta 773: 231–36Google Scholar
  29. 29.
    Panagia V, Singh JN, Anand-Srivastava MB, Pierce GN, Jasmin F, Dhalla NS (1984) Sarcolemmal alterations during the development of genetically determined cardiomyopathy. Cardiovasc Res 18: 567–72Google Scholar
  30. 30.
    Peterson DW, Napolitano CA, Griffith DW (1980) Spontaneous mechanical alternans in papillary muscle from atherosclerotic rabbits. Am J Physiol 239: H674–80Google Scholar
  31. 31.
    Plourde G, Lavoie JP, Rousseau-Migneron S, Nadeau A (1991) Validation of the polyethylene glycol precipitation technique for the characterization of rat ventricular β-adrenoreceptors. Anal Biochem 192: 426–28Google Scholar
  32. 32.
    Rosenthal HE (1967) A graphic method for the determination and presentation of binding parameters in a complex system. Anal Biochem 20: 525–32Google Scholar
  33. 33.
    Scatchard G (1949) The attraction of protein for small molecule and ions. Ann NY Acad Sci 51: 660–72Google Scholar
  34. 34.
    Schwartz A, Lindenmayer GE, Allen JC (1975) The sodium-potassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects. Pharmacol Rev 27: 3–134Google Scholar
  35. 35.
    Simons LA (1986) Interactions of lipids and lipoproteins with coronary artery disease mortality in 19 countries. Am J Cardiol 57: 5G-10GGoogle Scholar
  36. 36.
    Stason WB (1990) Cost and benefits of risk factor reduction for coronary heart disease: Insights from screening and treatment of serum cholesterol. Am Heart J 119: 718–24Google Scholar
  37. 37.
    Tibbits GF, Sasaki M, Ikeda M, Shimada K, Tsuruhara T, Nagatomo T (1981) Characterization of rat myocardial sarcolemma. J Moll Cell Cardiol 13: 1051–61Google Scholar
  38. 38.
    Tsuji K, Tsutsumi S, Ogawa K, Miyazaki Y, Satake T (1987) Cardiac alpha1 and beta adrenoreceptors in rabbits: effects of dietary sodium and cholesterol. Cardiovasc Res 21: 39–44Google Scholar
  39. 39.
    Uysal M (1986) Erythrocyte lipid peroxidation and (Na+−K+)-ATPase activity in cholesterol fed rabbits. Int J Vitam Nutr Res 56: 307–10Google Scholar
  40. 40.
    Van der Laarse A (1987) Cholesterol and myocardial membrane function. Basic Res Cardiol 82 suppl 1: 137–45Google Scholar
  41. 41.
    Vandamme D, Blaton V, Peeters H (1978) Screening of plasma lipids by thin-layer chromatography with flame ionization detection on chromarods. J Chromatogr 145: 151–54Google Scholar
  42. 42.
    Wu CC, Su MJ, Chi JF, Chen WJ, Hsu HC, Lee YT (1995) The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte. J Mol Cell Cardiol 27: 1263–69Google Scholar
  43. 43.
    Yeagle PL (1983) Cholesterol modatation of (Na+−K+) ATPase ATP hydrolyzing activity in the human erythrocyter. Biochim Biophys Acta 727: 39–44Google Scholar
  44. 44.
    Yeagle PL (1985) Cholesterol and the cell membrane. Biochim Biophys Acta 822: 267–87Google Scholar
  45. 45.
    Yeagle PL (1989) Lipid regulation of cell membrane structure and function. FASEB J 3: 1833–42Google Scholar

Copyright information

© Steinkopff Verlag 1997

Authors and Affiliations

  • W. -J. Chen
    • 1
  • S. -Y. Lin-Shiau
    • 2
  • H. -C. Huang
    • 2
  • Y. -T. Lee
    • 1
  1. 1.Department of Internal Medicine College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Department of Pharmacology College of MedicineNational Taiwan UniversityTaipeiTaiwan

Personalised recommendations