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Effects of riboflavin analogues and diuretics on the spontaneously hypertensive rat heart

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Summary

The chronic treatment of spontaneously hypertensive rats (SHR) with 7,8-dimethyl-10-(3-chlorobenzyl) isoalloxazine [CBI], 7,8-diethyl-10-aminol isoalloxazine [DEAI], enduron (methyclothiazide) and amiloride were studied for their effects on blood pressure and cardiac contractile protein ATPasc activities. After 35 weeks of treatment all the above antihypertensive agents showed a decrease in blood pressure in the SHR (p<0.01). Chronic treatment with CBI, DEAI, enduron, and amiloride significantly improved the myofibrillar ATPasc activity at all pCa2+ concentrations (p<0.01). Furthermore, CBI, DEAI, enduron, and amiloride drug treatments enhanced actin-activated myosin ATPase activity (p<0.01). The Ca2+-activated myosin ATPase activity was significantly elevated after treating with CBI and DEAI (p<0.01). These results suggest that the antihypertensive agents used in this study helped in reducing the blood pressure with a subsequent increase in myocardial contractile protein ATPase activity.

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References

  1. Buttrick P, Malhotra A, Factor S, Green D, Scheurer J (1988) Effects of chronic dobutaminc administration on hearts of normal and hypertensive rats. Circ Res 63:173–181

    PubMed  Google Scholar 

  2. Capasso JM, Strobeck JE, Malhotra A, Scheur J, Sonnenblick EH (1982) Contractile behavior of rat myocardium after reversal of hypertensive hypertrophy. Am J Physiol 242:H882-H889

    PubMed  Google Scholar 

  3. Effron MB, Bhatnagar GM, Spurgeon HA, Ruano-Arroyo G, Lakatta EG (1986) Changes in myosin isoenzymes. ATPase activity, and contraction duration in rat cardiac muscle with aging can be modulated by thyroxine. Circ Res 60:238–245

    Google Scholar 

  4. Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, Anderson W, Lambert G (1988) Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11:3–20

    PubMed  Google Scholar 

  5. Falkner B, Onesti G, Angelakos ET (1981) Effect of salt loading on the cardiovascular response to stress in adolescents. Hypertension 3, Suppl II:II-195–II-199

    Google Scholar 

  6. Falkner B, Onesti G, Angelakos ET, Fernandes M, Langman C (1979) Cardiovascular response to mental stress in normal adolescents with hypertensive parents: hemodynamics and mental stress in adolescents. Hypertension 1:23–30

    PubMed  Google Scholar 

  7. Fiske CH, Subba Row Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–380

    Google Scholar 

  8. Flink IL, Rader JH, Morkin E (1979) Thyroid hormone stimulates synthesis of a cardiac myosin isozyme. J Biol Chem 254:3105–3110

    PubMed  Google Scholar 

  9. Frishman WH, Skolnick AE, Strom JA (1989) Effects of calcium entry blockade on hypertension induced left ventricular hypertrophy. Circulation 80, Suppl IV:IV-151–IV-161

    Google Scholar 

  10. Hjalmarson AC, Whitfield CF, Morgan HE (1970) Hormonal control of heart function and myosin ATPase activity. Biochem Biophys Res Commun 41:1548–1589

    Google Scholar 

  11. Hoh JFY, McGrath PA, Hale PT (1978) Electrophoretic analysis of multiple forms of rat cardiac myosin: Effects of hypophyscctomy and thyroxine replacement. J Mol Cell Cardiol 10:1053–1076

    PubMed  Google Scholar 

  12. Hoh JF, McGrath PA, Hale TP (1977) Electrophoretic analysis of multiple forms of rat cardiac myosin: Effects of hypophysectomy and thyroxine replacement. J Mole Cell Cardio 10:1053–1076

    Google Scholar 

  13. Holroyde MJ, Howe E, Solaro RJ (1970) Modification of calcium requirements for activation of cardiac myofibrillar ATPase by cyclic AMP dependent phosphorylation. Biochem Biophys Acta 1979; 586:63–69

    Google Scholar 

  14. Institute of Laboratory Animal Resources (1976) Spontaneously hypertensive (SHR) rats: Guidelines for breeding, care and use. ILAR News 19:G1. Washington, DC, National Research Council

    Google Scholar 

  15. Jacob R, Kissling G, Ebrecht EJ, Jorg E, Rupp H, Takeda N (1984) Cardiac alterations at the myofibrillar level. Is a redistribution of the myosin isoenzyme pattern decisive for cardiac failure in haemodynamic overload. Eur Heart J, Suppl F:13–26

  16. Jacob R (1986) Cardiac responses to experimental chronic pressure overload. Handbook of hypertension, Vol 7:59–70

    Google Scholar 

  17. Jacob R, Ebrecht G, Holubarsch CH, Rupp H, Kissling G (1983) Mcchanics and energetics in cardiac hypertrophy as related to isoenzyme pattern of myosin Perspective in Cardiovascular Res 7:553–569

    Google Scholar 

  18. Jacob R (1986) Cardiac responses to experimental chronic pressure overload. Handbook of hypertension, Vol 7; Pathophysiology of hypertension-cardiovascular aspects: 59–63

    Google Scholar 

  19. Jouannot P, Hatt PY (1975) Rat myocardial mechanics during pressure-induced hypertrophy development and reversal. Am J Physiol 299:355–364

    Google Scholar 

  20. Kissling G, Gassenmaier T, Wendt-Gallitelli MF, Jacob R (1977) Pressure-volume relations, elastic modules, and contractile behaviour of the hypertrophied left ventricle of rats with Goldblatt II hypertension. Pflügers Arch 369:213–221

    Google Scholar 

  21. Kohlmann O Jr, Breshahan M, Gavras H (1984) Central and peripheral indices of sympathetic activity after blood pressure lowering with cnalapril (MK-421) or hydralazine in normotensive rats. Hypertension 6, Suppl I:I-1–I-6

    Google Scholar 

  22. Koike H, Ito K, Miyamoto M, Nishino H (1980) Effects of long-term blockade of angiotensin converting enzyme with captopril (SQ 14,225) on hemodynamics and circulating blood volume in SHR. Hypertension 2:299–303

    PubMed  Google Scholar 

  23. Laragh JH (1973) Vasoconstriction-volume analysis for understanding and treating hypertension. The use of renin and aldosterone profiles. Am J Med 55:261–274

    PubMed  Google Scholar 

  24. Lengsfeld M, Morano I, Ganten U, Ganten D, Caspar Ruegg J (1988) Gonadectomy and hormonal replacement changes systolic blood pressure and ventricular myosin isoenzyme pattern of spontancously hypertensive rats. Circ Res 63:1090–1094

    PubMed  Google Scholar 

  25. Ljung B, Ablad B, Drews L, Fellinins E, Kjellstedt A, Wallborg M (1976) Antihypertensive effect of metoprolol in spontaneously hypertensive rats. Clin Sci Mol Med 52:443–450

    Google Scholar 

  26. Lowry OH, Rosebrough NJ, Farr AL, Randalls RJ (1951) Protein measurement with the folin phenol reagent. Biol Chem 193:265–275

    PubMed  Google Scholar 

  27. Motz W, Strauer BE (1983) Nifedipine in the long-term management of hypertensive heart disease. Hypertension 5:1139–1144

    Google Scholar 

  28. Pagani ED, Solaro RJ (1983) Swimming exercise, thyroid state, and distribution of myosin isoenzymes in rat heart. Am J Physiol 245:H713-H720

    PubMed  Google Scholar 

  29. Pfeffer JM, Pfeffer MA, Fletcher P, Fishbein M, Braunwald E (1982) Favorable effects of therapy on cardiac performance in spontancously hypertensive rats. Am J Physiol 242:H776-H784

    PubMed  Google Scholar 

  30. Pfeffer JA, Pfeffer MA, Frohlich ED (1971) Validity of an indirect tail cuff method for determining systolic arterial pressure in unancsthetized normotensive and spontancously hypertensive rats. J Lab Clin Med 78:957–962

    PubMed  Google Scholar 

  31. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E (1982) Regression of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA 79:3310–3314

    PubMed  Google Scholar 

  32. Rovetto MJ, Murphy RA, Lefer AM (1970) Cardiac impairment in adrenal insufficiency in the cat: reduced adenosinetriphosphatase activity of myocardial contractile proteins. Circ Res 26:419–428

    PubMed  Google Scholar 

  33. Rupp H, Kissling G, Jacob R (1983) Hormonal and haemodynamic determinants of polymorphic myosin. Perspectives in cardiovascular Res 7:373–383

    Google Scholar 

  34. Rupp H (1982) Polymorphic myosin as the common determinant of myofibrillar ATPase in different hacmodynamic and thyroid state. Basic Res Cardiol 77:34–46

    PubMed  Google Scholar 

  35. Rupp H (1981) The adaptive changes in isoenzyme pattern of myosin from hypertrophied rat myocardium as a result pf pressure overload and physical training. Basic Res Cardiol 76:79–88

    PubMed  Google Scholar 

  36. Sartore S, Pierobon-Bormioli S, Schiaffino S (1978) Immunohistochemical evidence for myosin polymorphism in the chicken heart. Nature 274:82–83

    PubMed  Google Scholar 

  37. Scheuer J, Bhan AK (1979) Cardiac contractile proteins: Adenosine triphosphatase activity and physiological function. Circ Res 45:1–12

    PubMed  Google Scholar 

  38. Sen S (1987) Factors regulating myocardial hypertrophy in hypertension. Circulation 75:I-81–I-84

    Google Scholar 

  39. Sen S, Tarazi RC, Bumpus FM (1980) Effect of converting enzyme inhibitor (SQ 14,225) on myocardial hypertrophy in spontaneously hypertensive rats. Hypertension 2:169–176

    PubMed  Google Scholar 

  40. Sen S, Young D (1985) The role of sodium on modulation of myosin isoenzymes in renal hypertensive rats. Fed Proc 44:1653

    Google Scholar 

  41. Sheer D, Morkin E (1984) Myosin isoenzyme expression in rat ventricle: Effects of thyroid hormone analogs. Catecholamines, glucocorticoids and high carbohydrate diet. J Pharmacolol Expt Therapeutics 229:872–879

    Google Scholar 

  42. Shiverick KT, Thomas LL, Alpert NR (1975) Purification of cardiac myosin: Application to hypertrophied myocardium. Biochim Biophys Acta 393:124–133

    PubMed  Google Scholar 

  43. Solaro RJ, Pang DC, Briggs FN (1971) The purification of cardiac myofibrils with Triton X-100. Biochim Biophys Acta 245:259–262

    PubMed  Google Scholar 

  44. Sole MJ, Lo C-M, Laird CW, Sonnenblick WH, Wurtman RJ (1975) Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster. Circ Res 27:855–862

    Google Scholar 

  45. Spudich JA, Watt S (1971) The regulation of rabbit skeletal muscle contraction. J Biol Chem 246:4866–4871

    PubMed  Google Scholar 

  46. Swynghedauw B, Leger JJ, Schwartz K (1976) The myosin isoenzyme hypothesis in chronic heart overloading. J Mol Cell Cardiol 8:915–924

    PubMed  Google Scholar 

  47. Tarazi RC, Dustan HP, Frohlich ED (1970) Long-term thiazide therapy in essential hypertension. Circulation 41:709–717

    PubMed  Google Scholar 

  48. Trachewsky D (1981) Antihypertensive effect of riboflavin analogs in rats with mineralocorticoid induced hypertension. Hypertension 3:75–80

    PubMed  Google Scholar 

  49. Trachewsky D (1978) Aldosterone stimulation of riboflavin incorporation into rat renal flavin coenzymes and the effect of inhibition by riboflavin analogues on sodium reabsorption. J Clin Invest 62:1325–1333

    PubMed  Google Scholar 

  50. Trachewsky D, Kem DC (1985) Antihypertensive effect of riboflavin analogues in spontaneous hypertensive rats. J Lab Clin Med 106:223–228

    PubMed  Google Scholar 

  51. Udenfriend S, Spector S (1972) Spontaneously hypertensive rat. Science 176:1155–1156

    Google Scholar 

  52. Volicer L, Scheer E, Hilse H, Visweswaram D (1968) The turnover of norepinephrine in the heart during experimental hypertension in rats. Life Sci. 7:525–532

    PubMed  Google Scholar 

  53. Yazaki Y, Raben MS (1975) Effect of the thyroid state on the enzymatic characteristics of cardiac myosin. Circ Res 36:208–215

    Google Scholar 

  54. Wolfgang M, Straur BE (1985) Regression of cardiac hypertrophy after therapy in animal hypertension. J Cardiovasc Pharmacol 7, Suppl 2:556–561

    PubMed  Google Scholar 

  55. Maughan D, Low E, Litten R, Brayden J, Alpert N (1979) Calcium-activated muscle from hypertrophied rabbit heart. Circ Res 44:279–287

    PubMed  Google Scholar 

  56. Fuchs F (1974) Striated muscle. Annual Review of Physiology 36:461–501

    Google Scholar 

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Author notes

  1. Y. S. Reddy

    Present address: Department of Physiology and Biophysics, University of Oklahoma Health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, Oklahoma, USA

Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Oklahoma Health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, Oklahoma, USA

    M. Bhaskar, D. Trachewsky & R. D. Stith

  2. Department of Medicine, University of Oklahoma Health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, Oklahoma, USA

    M. Bhaskar, D. Trachewsky, R. D. Stith & Y. S. Reddy

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Bhaskar, M., Trachewsky, D., Stith, R.D. et al. Effects of riboflavin analogues and diuretics on the spontaneously hypertensive rat heart. Basic Res Cardiol 85, 444–452 (1990). https://doi.org/10.1007/BF01931490

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  • DOI: https://doi.org/10.1007/BF01931490

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