Advertisement

Neurochemical Indices of Autonomic Innervation of Heart in Different Experimental Models of Heart Failure

  • Donald D. Lund
  • Phillip G. Schmid
  • Robert RoskoskiJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 161)

Abstract

Parasympathetic neural regulation of the failing heart is impaired. In order to investigate parasympathetic mechanisms in experimental heart failure, measurements were made of choline acetyl-transferase CCAT) activity and [3H]-quinuclidinyl benzilate (QNB) binding in hearts of 1) hamsters with skeletal and cardiac myopathy, 2) dogs with pulmonary artery constriction and tricuspid avulsion, and 3) guinea pigs with pulmonary artery constriction. Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities and norepinephrine levels served as indices of sympathetic innervation. In myopathic hearts, total CAT activity decreased (P<0.05) compared to age-matched controls. In canine and guinea pig right heart failure, total CAT activity was normal in contractile and specialized tissues. Alterations in [3h]-QNB binding paralleled CAT activity being decreased (P<0.05) only in myopathic hearts. In all three models, indices of sympathetic innervation were altered in ways qualitatively different from parasympathetic indices; TH and DBH activities were increased (P<0.05) in myopathic ventricles, decreased (P<0,05) in hypertrophied canine and guinea pig ventricles and non-hypertrophied canine ventricles, and normal in non-hypertrophied guinea pig ventricles. These results indicate that alterations in cardiac parasympathetic indices vary depending on the etiology of heart diseases and differ qualitatively from alterations in sympathetic indices. Selective determinants are necessary to explain the varied changes.

Keywords

Tyrosine Hydroxylase Sympathetic Innervation Syrian Golden Hamster Circulation Research Cholinergic Muscarinic Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Afifi, A.A., and Azen, S.P. Statistical Analysis: A Computer Oriented Approach. Academic Press, New York, p 75 (1972).Google Scholar
  2. 2.
    Anderson, R.H. The disposition, morphology and innervation of cardiac specialized tissue in the guinea pig. Journal of Anatomy 111, 453 (1972).PubMedGoogle Scholar
  3. 3.
    Angelakos, E.T., King, M.P., and Carballo, L. Cardiac adrenergic innervation in hamsters with hereditary myocardiopathy: chemical and histochemical studies, In Recent Advances in Studies on Cardiac Structure and Metabolism, vol. 2, edited by E. Bajusz, and G. Rona. Baltimore, University Park Press, pp 529–532 (1973).Google Scholar
  4. 4.
    Bajusz, E., Homburger, F., Baker, J.R., and Opie, L.H. The heart muscle in muscular dystrophy with special reference to involvement of the cardiovascular system in the hereditary myopathy of the hamster. Annals of the New York Academy of Science 138, 213–231 (1966).CrossRefGoogle Scholar
  5. 5.
    Bajusz, E., Homburger, F., Baker, J.R., and Bogdonoff, P. Dissociation of factors influencing myocardial degeneration and generalized circulatory failure. Annals of New York Academy of Science 156, 396–420 (1969).CrossRefGoogle Scholar
  6. 6.
    Barger, A.C., Roc, B.B., and Richardson, G.S. Relations of valvular lesions and of exercise to auricular pressure, work tolerance, and to development of chronic congestive failure in dogs. American Journal of Physiology 169, 384–399 (1952).PubMedGoogle Scholar
  7. 7.
    Borchard, F. The adrenergic nerves of the normal and hyper-trophied heart. In Normal and Pathological Anatomy, Vol. 33, edited by W. Bargmann and W. Doerr, P.S.G. Publishing Company, Inc., Massachusetts, pp 1–68.Google Scholar
  8. 8.
    Chidsey, CA., Kaiser, G.A., Sonnenblick, E.H., Spann, J.F. Jr., and Braunwald, E. Cardiac norepinephrine stores in experimental heart failure in dogs. Journal of Clinical Investigation 43, 2389–2393 (1964).CrossRefGoogle Scholar
  9. 9.
    Covell, J.W., Chidsey, C.A., and Braunwald, E. Reduction of cardiac response to postganglionic sympathetic nerve stimulation in experimental heart failure. Circulation Research 19, 51–56 (1966).Google Scholar
  10. 10.
    Coyle, J.T. Tyrosine hydroxylase in rat brain. Cofactor requirments, regional and subcellular distribution. Biochemical Pharmacology 21, 1935–1944 (1972).PubMedCrossRefGoogle Scholar
  11. 11.
    Coyle, J.T., and Axelrod, J. Dopamine-β-hydroxylase in the rat brain. Developmental characteristics. Journal of Neurochemistry 19, 449–459 (1972).PubMedCrossRefGoogle Scholar
  12. 12.
    Crockatt, L.H., Lund, D.D., Schmid, P.G., and Roskoski, R. Jr. Hypoxia-induced changes in parasympathetic neurochemical markers in guinea pig heart. Journal of Applied Physiology: Respiration Environmental Exercise Physiology 50, 1017–1021 (1981).Google Scholar
  13. 13.
    Eckberg, D.L., Drabinsky, M., and Braunwald, E. Defective cardiac parasympathetic control in patients with heart disease. New England Journal of Medicine 285, 877–883 (1971).PubMedCrossRefGoogle Scholar
  14. 14.
    Galper, J.G., Klein, W., and Catterall, W.A. Muscarinic acetylcholine receptor in developing chick heart. Journal of Biological Chemistry 252, 8692–8699 (1977).PubMedGoogle Scholar
  15. 15.
    Higgins, C.B., Vatner, S.F.., Eckberg, D.L., and Braunwald, E. Alterations in the baroreceptor reflex in conscious dogs with heart failure. Journal of Clinical Investigation 51, 715–724 (1972).PubMedCrossRefGoogle Scholar
  16. 16.
    Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. Protein measurement with folin phenol reagent. Journal of Biological Chemistry 193, 265–275 (1951).PubMedGoogle Scholar
  17. 17.
    Lund, D.D., Schmid, P.G., Kelley, S.E., Corry, R.J., and Roskoski, R. Jr. Choline acetyltransferase activity in rat heart after transplantation. American Journal of Physiology 235, H367-H371 (1978).PubMedGoogle Scholar
  18. 18.
    Lund, D.D., Schmid, P.G., Johannsen, U.J., and Roskoski, R. Jr. Biochemical indices of cholinergic and adrenergic autonomic innervation in dog heart: Disparate alterations in chronic right heart failure. Journal of Molecular and Cellular Cardiology (In press).Google Scholar
  19. 19.
    Pool, P.E., Covell, J.W., Levitt, M., Gibb, J., and Braunwald, E. Reduction of cardiac tyrosine hydroxylase activity in experimental congestive heart failure. Circulation Research 20, 349–353 (1967).PubMedGoogle Scholar
  20. 20.
    Roskoski, R. Jr., Mayer, H.E., and Schmid, P.G, Choline acetyltransferase activity in guinea pig in vitro. Journal of Neurochemistry 23, 1197–1200, 1974.PubMedCrossRefGoogle Scholar
  21. 21.
    Roskoski, R. Jr., Schmid, P.G., Mayer, H.E., and Abboud, F.M. In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts. Circulation Research 36, 547–552 (1975).PubMedGoogle Scholar
  22. 22.
    Schmid, P.G., Mayer, H.E., Mark, A.L., Heistad, D.D., and Abboud, F.M. Differences in the regulation of vascular resistance in guinea pigs with right and left heart failure. Circulation Research 41, 85–93 (1977).PubMedGoogle Scholar
  23. 23.
    Schmid, P.G., Greif, B.J., Lund, D.D., and Roskoski, R. Jr. Regional choline acetyltransferase activity in guinea pig heart. Circulation Research 42, 657–660 (1978).PubMedGoogle Scholar
  24. 24.
    Schmid, P.G., Lund, D.D., and Roskoski, R. Jr. Efferent autonomic dysfunction in heart failure. In Disturbances in Neurogenic Control of Circulation. Edited by F.M. Abboud, H.A. Fozzard, J.P. Gilmore, and D.J. Reis, Bethesda: American Physiological Society, pp 33–49 (1981).Google Scholar
  25. 25.
    Schmid, P.G., Lund, D.D., Davis, J.A., Whiteis, C.A., Bhatnagar, R.K., and Roskoski, R. Jr. Selective sympathetic neural changes in hypertrophied right ventricle. American Journal of Physiology (In press).Google Scholar
  26. 26.
    Schmidt, R.H., and Bhatnagar, R.K. Regional development of norepinephrine, dopamine-β-hydroxylase, and tyrosine hydroxylase in the rat brain subsequent to neonatal treatment with subcutaneous 6-hydroxydopamine. Brain Research 166, 293–308 (1979).PubMedCrossRefGoogle Scholar
  27. 27.
    Sole, M.J., Lo, C., Liard, C.W., Sonnenblick, E.H., and Wurtman, R.J. Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster. Circulation Research 37, 855–862 (1975).PubMedGoogle Scholar
  28. 28.
    Sole, M.J., Wurtman, R.J., Lo, C.M., Ramble, A.B., and Sonnenblick, E.H. Tyrosine hydroxylase activity in the heart of the cardiomyopathic Syrian hamster. Journal of Molecular and Cellular Cardiology 9, 225–233, (1977).PubMedCrossRefGoogle Scholar
  29. 29.
    Sole, M.J., and Hussain, M.N. A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster. Circulation Research 41, 814–817 (1977).PubMedGoogle Scholar
  30. 30.
    Spann, J.F. Jr., Chidsey, C.A., Pool, P.E., and Braunwald, E. Mechanisms of norepinephrine depletion in experimental heart failure produced by aortic constriction in the guinea pig. Circulation Research 17, 312–321 (1965).PubMedGoogle Scholar
  31. 31.
    Strobeck, J.E., Factor, S.M., Ghan, A., Sole, M., Liew, C.C., Fein, F., and Sonnenblick, E.H. Hereditary and acquired cardiomyopathies in experimental animals: Mechanical, biochemical, and structural features. Annals of New York Academy of Science 317, 59–88 (1979).Google Scholar
  32. 32.
    White, C.W., Marcus, M.L., and Abboud, F.M. Distribution of coronary artery flow to the canine right atrium and sinoatrial node. Circulation Research 40, 342–347 (1977).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Donald D. Lund
    • 1
  • Phillip G. Schmid
    • 1
  • Robert RoskoskiJr.
    • 1
  1. 1.VA Medical Center, The Cardiovascular Center, and Departments of Internal Medicine and BiochemistryThe University of IowaIowa CityUSA

Personalised recommendations