Skip to main content
SpringerLink
Log in

Reduced cAMP levels and glycogen phosphorylase activation in isoproterenol perfused SHR myocardium

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

The effect of isoproterenol perfusion on cAMP levels and phosphorylase activity was investigated in the spontaneously hypertensive rat (SHR) and Kyoto Wistar normotensive control rat (WKY) heart. The basal force of contraction in physiological salt solution perfused hearts was comparable between SHR and WKY. However, the force of contraction in response to 10 nM isoproterenol perfusion was decreased approximately 20–30% in SHR heart as compared to WKY heart. Basal cAMP levels were reduced in SHR hearts as compared to WKY heart. Isoproterenol perfusion resulted in an increase in cAMP levels over the basal cAMP values which was 50% and 100% in SHR and WKY hearts, respectively. Basal phosphorylase activity was higher in SHR hearts as compared to WKY hearts. However, the percentage increase in phosphorylase activity by isoproterenol perfusion over the basal values was approximately 400% in WKY hearts and only 200% in SHR hearts. The oubain-sensitive (Na+, K+)-ATPase activity, Ca2+ binding in the absence of ATP, sialic acid content, and 5′-nucleotidase activity of purified cardiac plasma membranes was not altered in SHR as compared to WKY. These results would suggest β-adrenergic mediated adenylate cyclase stimulation is decreased in SHR myocardium while other plasma membrane properties and associated enzymes may not be altered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Amer, M. S., N. Doba, D. J. Reis: Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension. Proc. Natl. Acad. Sci. (U.S.A.)72, 2135–2139 (1975).

    Google Scholar 

  2. Averill, D. B., C. M. Ferrario, R. C. Tarazi, S. Sen, R. Bajluis: Cardiac performance in rats with renal hypertension. Circulat. Res.38, 280–288 (1976).

    PubMed  Google Scholar 

  3. Bers, D. M.: Isolation and characterization of cardiac sarcolemma. Biochim. biophys. acta555, 131–146 (1979).

    PubMed  Google Scholar 

  4. Bers, D. M., G. A. Langer. Uncoupling cation effects on cardiac contractility and sarcolemmal Ca2+ binding. Amer. J. Physiol.237, H332-H341 (1979).

    PubMed  Google Scholar 

  5. Bhalla, R. C., T. Ashley: Altered function of adenylate cyclase in the myocardium of the spontaneously hypertensive rat. Biochem. Pharmacol.27, 1967–1971 (1978).

    PubMed  Google Scholar 

  6. Bhalla, R. C., R. V. Sharma, T. Ashley: Adenylase cyclase activity in myocardium of spontaneously hypertensive rat: effect of endogenous factors and solubilization. Biochem Biophys. Res. Commun.82, 273–280 (1978).

    PubMed  Google Scholar 

  7. Bhalla, R. C., R. V. Sharma, S. Ramanathan: Ontogenetic development of isoproterenol subsensitivity of myocardial adenyslate cyclase and β-adrenergic receptors in spontaneously hypertensive rats. Biochim. biophys. acta632, 497–506 (1980).

    PubMed  Google Scholar 

  8. Blaustein, M. P.: Sodium ions, calcium ions, blood pressure regulation and hypertension: a reassesment and a hypothesis. Amer. J. Physiol.232, 165–173 (1977).

    Google Scholar 

  9. Bradford, M. M.: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem.72, 248–254 (1976).

    PubMed  Google Scholar 

  10. Caroni, P., E. Carafoli: Regulation of Ca2+-pumping ATPase of heart sarcolemma by a phosphorylation-dephosphorylation process. J. Biol. Chem.256, 9371–9373 (1981).

    PubMed  Google Scholar 

  11. Edwards, M. J., M. H. Maguire: Purification and properties of rat heart 5′-nucleotidase. Mol. Pharmacol6, 641–648 (1970).

    PubMed  Google Scholar 

  12. Fiske, C. H., Y. SubbaRow: The colorimetric determination of phosphorus. J. Biol. Chem.66, 375–400 (1925).

    Google Scholar 

  13. Frank, J. S., G. A. Langer, L. M. Nudd, K. Seraydarian: The myocardial cell surface, its histochemistry, and the effect of sialic acid calcium removal on its structure and cellular ionic exchange. Circulat. Res.41, 702–714 (1977).

    PubMed  Google Scholar 

  14. Fujiwara, M., M. Kuchii, S. Shibata: Differences of cardiac reactivity between spontaneously hypertensive and normotensive rats. Eur. J. Pharmacol.19, 1–11 (1972).

    PubMed  Google Scholar 

  15. Gilboe, D. P., K. L. Larson, F. Q. Nuttall: Radioactive method for the assay of glycogen phosphorylases. Anal. Biochem.47, 20–27 (1972).

    PubMed  Google Scholar 

  16. Godfraind, T., D. T. Lutete: Inhibition by Digoxin and 5C4453 of (Na+K+)-ATPase prepared from human heart, guinea pig heart and guinea pig brain. Eur. J. Pharmacol.60, 329–336 (1979).

    PubMed  Google Scholar 

  17. Gross, S. R., S. E. Meyer: Regulation of phosphorylase b to a conversion in muscle. Life Sci.14, 401–414 (1974).

    PubMed  Google Scholar 

  18. Hayes, J. S., L. L. Brunton, J. H. Brown, J. B. Reese, S. E. Mayer: Hormonally specific expression of cardiac protein kinase activity. Proc. Natl. Acad. Sci. (U.S.A.)76, 1570–1574 (1979).

    Google Scholar 

  19. Hayes, J. S., S. E. Brunton, S. E. Mayer: Selective activation of particulate cAMP-dependent protein kinase by isoproterenol and prostaglandin E1. J. Biol. Chem.255, 5113–5119 (1980).

    PubMed  Google Scholar 

  20. Hayes, J. S., S. E. Mayer: Regulation of guinea pig heart phosphorylase kinase by cAMP, protein kinase, and calcium. Amer. Physiol.240, E340-E349 (1981).

    Google Scholar 

  21. Huang, W., H. M. Rhee, T. H. Chiu, A. Askari: Re-evaluation of the relationship between the positive inotropic effect of ouabain and its inhibitory effect on (Na+ +K+)-dependent adenosine triphosphatase in rabbit and dog hearts. J. Pharmacol. Exp. Therap.211, 571–582 (1979).

    Google Scholar 

  22. Keely, S. L., J. D. Corbin: Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force. Amer. J. Physiol.233, H269-H275 (1977).

    PubMed  Google Scholar 

  23. Kirchberger, M. A., D. Wong: Calcium efflux from isolated cardiac sarcoplasmic reticulum. J. Biol. Chem.253, 6941–6945 (1978).

    PubMed  Google Scholar 

  24. Kopp, S. J., M. Bárány: Phosphorylation of the 19,00-dalton light chain of myosin in perfused rat heart under the influence of negative and positive inotropic agents. J. Biol. Chem.254, 12007–12012 (1979).

    Google Scholar 

  25. Langer, G. A.: The structure and function of the myocardial cell surface. Amer. J. Physiol.235, H461-H468 (1978).

    PubMed  Google Scholar 

  26. Langer, G. A.: The role of calcium in the control of myocardial contractility: An update. J. Mol. Cell. Cardiol.12, 231–239 (1980).

    PubMed  Google Scholar 

  27. Langer, G. A., J. S. Frank, L. M. Nudd, K. Seraydarian: Sialic acid: Effect of removal on calcium exchangeability of cultured heart cells. Science193, 1013–1015 (1976).

    PubMed  Google Scholar 

  28. Limas, C. J., J. N. Cohn: Defective calcium transport by cardiac sarcoplasmic reticulum in spontaneously hypertensive rats. Circulat. Res.40 (Suppl. I), 162–169 (1977).

    Google Scholar 

  29. McCullough, T. E., D. A. Walsh: Phosphorylation and dephosphorylation of phosphorylase kinase in the perfused rat heart. J. Biol. Chem.254, 7345–7352.

  30. Nayler, W. G., P. Greenwald: Calcium entry blockers and myocardial function. Fed. Proc.40, 2855–3661 (1981).

    PubMed  Google Scholar 

  31. Okamoto, K., K. Aoki: Development of a strain of spontaneously hypertensive rats. Jap. Circ. J.27, 282 (1963).

    PubMed  Google Scholar 

  32. Pfeffer, M. A., J. M. Pfeffer, E. D. Frolich: Hemodynamics of the spontaneously hypertensive rat: effects of isoproterenol. Proc. Soc. Exp. Biol. Med.145, 1025–1030 (1974).

    PubMed  Google Scholar 

  33. Philipson, K. D., D. M. Bers, A. Y. Nishimoto, G. A. Langer: Binding of Ca2+ and Na2+ to sarcolemmal membranes: relation to control of myocardial contractility. Amer. J. Physiol.238, H373-H378 (1980).

    PubMed  Google Scholar 

  34. Philipson, K. D., G. A. Langer: Sarcolemmal-bound calcium and contractility in the mammalian myocardium. J. Mol. Cell. Cardiol.11, 857–875 (1979).

    PubMed  Google Scholar 

  35. Pollack, G. H.: Cardiac pacemaking: An obligatory role of catecholamines? Science196, 731–738 (1977).

    PubMed  Google Scholar 

  36. Saragoca, M., R. C. Tarazi: Impaired cardiac contractile response to isoproterenol in the spontaneously hypertensive rat. Hypertension3, 380–385 (1981).

    PubMed  Google Scholar 

  37. Schwartz, A.: Cell membrane (Na+, K+)-ATPase and sarcoplasmic reticulum, possible regulations of intracellular ion activity. Fed. Proc.35, 1279–1282 (1976).

    PubMed  Google Scholar 

  38. Sharma, R. V., D. B. Kemp, R. C. Gupta, R. C. Bhalla: Properties of adenylate cyclase in the cardiovascular tissues of renal hypertensive rats. J. Cardiovasc. Pharmacol.4, 622–628 (1982).

    PubMed  Google Scholar 

  39. Shenolikar, S., P. T. W. Cohen, P. Cohen, A. C. Nairn, S. V. Perry: The role of calmodulin in the structure and regulation of phosphorylase kinase from rabbit skeletal muscle. Eur. J. Biochem.100, 329–337 (1979).

    PubMed  Google Scholar 

  40. Stull, J. T., S. E. Meyer: Biochemical mechanisms of adrenergic and cholinergic regulation of myocardial contractility. In: Handbook of Physiology: The Cardiovascular System, edited by R. M. Berne, N. Sperelakis, S. R. Geiger. Baltimore, Williams and Williams, pp. 741–774 (1979).

    Google Scholar 

  41. Tada, M., M. A. Kirchberger, D. I. Repke, A. M. Katz: The stimulation of calcium transport in cardiac sarcoplasmic reticulum by 3′:5′-monophosphate-dependent protein kinase. J. Biol. Chem.249, 6174–6180 (1974).

    PubMed  Google Scholar 

  42. Triner, L., Y. Vulliemoz, M. Verosky, W. M. Manger: Cyclic adenosine monophosphate and vascular reactivity in spontaneously hypertensive rats. Biochem. Pharmacol.24, 743–745 (1975).

    PubMed  Google Scholar 

  43. Warren, L.: The thiobarbituric acid assay of sialic acids. J. Biol. Chem.234, 1971–1975 (1959).

    PubMed  Google Scholar 

  44. Werth, D. K., D. R. Hathaway, A. M. Watanabe: Regulation of phosphorylase kinase in rat ventricular myocardium. Role of calmodulin. Circulat. Res.51, 448–456.

  45. Woodcock, E. A., J. W. Funder, C. L. Johnston: Decreased cardiac β-adrenergic receptors in deoxycorticosterone-salt and renal hypertensiver rats. Circulat. Res.45, 560–565 (1979).

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. R. V. Sharma

    Present address: Department of Anatomy, The University of Iowa, College of Medicine, 52242, Iowa City, Iowa, (USA)

Authors and Affiliations

  1. Department of Anatomy, The University of Iowa, College of Medicine, 52242, Iowa City, Iowa, (USA)

    R. C. Gupta, M. Ramanadham, R. C. Venema & R. C. Bhalla

  2. The Cardiovascular Center, The University of Iowa, College of Medicine, 52242, Iowa City, Iowa, (USA)

    R. V. Sharma, R. C. Gupta, M. Ramanadham, R. C. Venema & R. C. Bhalla

Authors
  1. R. V. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. C. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Ramanadham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. C. Venema
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. C. Bhalla
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by NIH Grants HL19027 and HL14388 and grant-inaid from the Iowa Heart Association.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, R.V., Gupta, R.C., Ramanadham, M. et al. Reduced cAMP levels and glycogen phosphorylase activation in isoproterenol perfused SHR myocardium. Basic Res Cardiol 78, 695–705 (1983). https://doi.org/10.1007/BF01907217

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907217

Key words

Search

Navigation