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Dexamethasone treatment improves sarcoplasmic reticulum function and contractile performance in aged myocardium

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Abstract

Corticosteroids are thought to be involved in the maintenance of normal myocardial function by mechanisms incompletely understood. This study investigated the potential therapeutic benefit of the synthetic glucocorticoid, dexamethasone, in reversing age-associated deterioration in cardiac contractile performance and Ca2+ sequestration function of the sarcoplasmic reticulum. Dexamethasone was administered to senescent (26–28-month old), male Fischer 344 rats at a rate of 4 μg/h for 5 days via subcutaneously implanted osmotic mini pumps. Control rats received vehicle solution in similar manner. Contractile performance was assessed in Langendorff-perfused, electrically paced hearts from control and dexamethasone-treated rats. The results obtained showed that dexamethasone-treatment of aged rats resulted in significant improvement in myocardial contractile performance as evidenced by (i) increase (∼30–60%) in developed peak tension at a wide range of beating frequencies (2–6 Hz), (ii) unaltered time to peak tension, and (iii) decrease (∼8–15%) in time to half-relaxation. Also, SR isolated from dexamethasone-treated rats displayed ∼2-fold higher rates of ATP-energized Ca2+ uptake compared to SR from control rats. The deficits in contractile performance of the senescent heart (prolonged contraction duration and diminished contractile force) are reversible through a glucocorticoid-mediated improvement in SR Ca2+ pump function (Mol Cell Biochem 266: 31–36, 2004)

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References

  1. Lakatta EG: Cardiac muscle changes in senescence. Annu Rev Physiol 49: 519–531, 1987

    Google Scholar 

  2. Lakatta EG: Cardiovascular regulatory mechanisms in advanced age. Annu Rev Physiol 73: 413–467, 1993

    Google Scholar 

  3. Jiang MT, Moffat MP, Narayanan N: Age-related alterations in the phosphorylation of sarcoplasmic reticulum and myofibrillar proteins and diminished contractile response to isoproteranol in intact rat ventricle. Circ Res 72: 102–111, 1993

    Google Scholar 

  4. Froelich JP, Lakatta EG, Beard E, Spurgeon HA, Weisfeldt ML, Gerstenblith G: Studies of sarcoplasmic reticulum function and contraction duration in young adult and aged rat myocardium. J Mol Cell Cardiol 10: 427–438, 1978

    Google Scholar 

  5. Gerstenblith G, Frederiksen J, Yin FC, Fortuin NJ, Lakatta EG, Weisfeldt ML: Echocardiographic assessment of a normal adult aging population. Circulation 56: 273–278, 1977

    Google Scholar 

  6. Lakatta EG, Gerstenblith G, Angell CS, Shock NW, Weisfeldt ML: Prolonged contraction duration in aged myocardium. J Clin Invest 55: 61–68, 1975

    Google Scholar 

  7. Narayanan N: Differential alterations in ATP-supported calcium transport activities of sarcoplasmic reticulum and sarcolemma of aging myocardium. Biochim Biophys Acta 678: 442–459, 1981

    Google Scholar 

  8. Narayanan N: Comparison of ATP-dependent calcium transport and calcium ATPase activities of cardiac sarcoplasmic reticulum and sarcolemma from rats of various ages. Mech Ageing Dev 38: 127–143, 1987

    Google Scholar 

  9. Tate CA, Taffet GE, Hudson EK, Blaylock SL, McBride RP, Michael LH: Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained old rats. Am J Physiol 258: H431–H435, 1990

    Google Scholar 

  10. Hoffman FG, Sobel EH: Adrenocortical insufficiency. In: H.W. Deane, BL. Rubin (eds). The Adrenocortical Hormones. Springer, Berlin, 1964, pp 27–183.

    Google Scholar 

  11. Lefer AM: Influence of glucocorticoids on the mechanical performance of isolated rat papillary muscle. Am J Physiol 214: 518–524, 1968

    Google Scholar 

  12. Penefsky ZJ, Kahn M: Inotropic effects of dexamethasone in mammalian heart muscle. Eur J Pharmacol 15: 259–266, 1971

    Google Scholar 

  13. Narayanan N: Effects of adrenalectomy and in vivo administration of dexamethasone on ATP-dependent calcium accumulation by sarcoplasmic reticulum from rat heart. J Mol Cell Cardiol 15: 7–15, 1983

    Google Scholar 

  14. Su N, Narayanan N: Enhanced chronotropic and ionotropic responses of rat myocardium to cholinergic stimulus with aging. Can J Physiol Pharmacol 70: 1618–1624, 1992

    Google Scholar 

  15. Jones DL, Narayanan N: Defibrillation depresses heart sarcoplasmic reticulum calcium pump: A mechanism of post-shock dysfunction. Am J Physiol 274: H98–H105, 1998

    Google Scholar 

  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with phenol reagent. J Biol Chem 193: 265–275, 1951

    Google Scholar 

  17. Fabiato A: A computer program for calculating total from specified free or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands. Methods Enzymol 157: 378–417, 1988

    Google Scholar 

  18. Capasso JM, Malhotra A, Remily RM, Scheuer J, Sonnenblick EH: Effects of aging on mechanical and electrical performance of rat myocardium. Am J Physiol 245: H72–H81, 1983

    Google Scholar 

  19. Guarnieri T, Filburn CR, Zitnik G, Roth GS, Lakatta EG: Contractile and biochemical correlates of β-adrenergic stimulation of the aged heart. Am J Physiol 239: H501–H508, 1980

    Google Scholar 

  20. Lakatta EG, Gerstenblith G, Angell CS, Shock NW, Weisfeldt ML: Diminished inotropic responses of aged myocardium to catecholamines. Circ Res 36: 262–269, 1975

    Google Scholar 

  21. Bassani JWM, Yuan W, Bers DM: Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes. Am J Physiol 268: C1313–C1319, 1995

    Google Scholar 

  22. Fabiato A: Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned cardiac pukinje cell. J Gen Physiol 85: 241–320, 1985

    Google Scholar 

  23. Janczewski AM, Spurgeon HA, Stern MD, Lakatta EG:Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells. Am J Physiol 268:H916–H920, 1995

    Google Scholar 

  24. Stern MD: Theory of excitation-contraction coupling in cardiac muscle. Biophys J 63: 497–517, 1992

    Google Scholar 

  25. Wier WG, Egan TM, Lopez-Lopez JR, Balke CW: Local control of excitation-contraction coupling in rat heart cells. J Physiol Lond 474: 463–471, 1994

    Google Scholar 

  26. Farrar RP, Starnes JW, Cartee GD, Oh PY, Sweeney HL: Effects of exercise on cardiac myosin isozyme composition during the aging process. J Appl Physiol 64: 880–883, 1988

    Google Scholar 

  27. Syrovy I: Changes in rat ventricular myosin in old age. Experientia Basel 40: 99–100, 1984

    Google Scholar 

  28. Levitan ES, Hershman KM, Sherman TG, Takimoto K: Dexamethasone and stress upregulate Kv1.5 K+ channel gene expression in rat ventricular myocytes. Neuropharmacology 35: 1001–1006, 1996

    Google Scholar 

  29. Taffet GE, Tate CA: Ca2+-ATPase content is lower in cardiac sarcoplasmic reticulum isolated from old rats. Am J Physiol 264: H1609–H1614, 1993

    Google Scholar 

  30. Schmidt U, del Monte F, Miyamoto MI, Matsui T, Gwathmey JK, Rosenzweig A, Hajjar RJ: Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca2+-ATPase. Circulation 101: 790–796, 2000

    Google Scholar 

  31. Frolkis VV, Bogatskaya LN, Shevchuk VG: Aging of the cardiocytes. In: V.V. Frolkis (ed.). Physiology of Cell Aging. S. Karger, Basel, 1984, pp 89–110

  32. Narayanan N, Khandelwal RL: Microsomal phosphorylase in rat heart: Depletion following adrenalectomy and restoration by in vivo adminis-tration of dexamethsaone. Endocrinology 117: 1544–1549, 1985

    Google Scholar 

  33. Xu KY, Zweier JL, Becker LC: Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport. Circ Res 77: 88–97, 1995

    Google Scholar 

  34. Sapolsky RM: The adrenal cortical axis. In: E.L. Schneider, J.W. Rowe (eds.). Handbook of the Biology of Aging, 3rd edn. Academic Press, San Diego, 1990, pp. 330–346

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, The University of Western Ontario, London, Ontario, Canada.

    Njanoor Narayanan, Chengxin Yang & Ande Xu

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  1. Njanoor Narayanan
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  2. Chengxin Yang
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  3. Ande Xu
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Narayanan, N., Yang, C. & Xu, A. Dexamethasone treatment improves sarcoplasmic reticulum function and contractile performance in aged myocardium. Mol Cell Biochem 266, 31–36 (2004). https://doi.org/10.1023/B:MCBI.0000049130.58074.73

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