Aging Clinical and Experimental Research

, Volume 7, Issue 4, pp 210–217 | Cite as

Effect of age on cardiac norepinephrine release in the female rat

  • David L. Snyder
  • M. D. Johnson
  • B. A. Eskin
  • W. Wang
  • J. Roberts
Original Article


We previously demonstrated an age-related decline in K+- induced norepinephrine (NE) release from cardiac synaptosomes prepared from 6- and 24- month- old male F344 rats. The purpose of the present study was to determine if the age- related decrease in NE release seen in male F344 rats is also present in female F344 rats. K+- induced NE release was assessed in cardiac synaptosomes prepared from 6-, 12-, 18-, and 24- month- old male and female F344 rats. NE release was significantly greater in young male rats, compared to old male rats. However, no age- related decrease in NE release was observed in the female rats. In contrast to previous observations in male rats, raising extracellular [Mg2+], an inorganic Ca2+ channel blocker, reduced NE release to the same extent in all female ages. Omega- conotoxin, an organic Ca2+ channel blocker, also decreased NE release to the same extent in all female ages. These studies suggest that in contrast to aging male rats, cardiac adrenergic nerve terminals of aging female rats maintain their capacity to release NE. (Aging Clin. Exp. Res. 7: 210–217, 1995)


Heart norepinephrine synaptosomes 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aloyo V.J., McIlvain H.B., Bhavsar V.H., Roberts J.: Characterization of norepinephrine accumulation by a crude synaptosomal-mitochondrial fraction isolated from rat heart. Life Sci. 48: 1317–1324, 1991.PubMedCrossRefGoogle Scholar
  2. 2.
    Snyder D.L., Aloyo V.J., McIlvain B., Johnson M.D., Roberts J.: Effect of potassium- and tyramine-induced release of norepinephrine from cardiac synaptosomes in male F344 rats. J. Gerontol. 47: B190–B197, 1992.PubMedCrossRefGoogle Scholar
  3. 3.
    Whittaker V.P.: The synaptosome. In: Lajtha A. (Ed.), Handbook of Neurochemistry. Plenum Press New York, 1984, Vol. 7, pp. 1–39.Google Scholar
  4. 4.
    de Belleroche J.S., Bradford H.F.: The stimulus-induced release of acetylcholine from synaptosome beds and its calcium dependence. J. Neurochem. 19: 1817–1819, 1972.PubMedCrossRefGoogle Scholar
  5. 5.
    Verhage M., Besselsen E., Loper da Silva F.H., Ghijsen W.E.J.M.: Ca2+-dependent regulation of presynaptic stimulussecretion coupling. J. Neurochem. 53: 1188–1194, 1989.PubMedCrossRefGoogle Scholar
  6. 6.
    McCleskey E.W., Fox A.P., Feldman D.H., Cruz L.J., Olivera B.M., Tsien R.W., Toshikami D.: ω-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle. Proc. Natl. Acad. Sci. USA 84: 4327–4331, 1987.PubMedCrossRefGoogle Scholar
  7. 7.
    Witcher D.R., De Waard M., Sakamoto J., Franzini-Armstrong C., Pragnell M., Kahl S.D., Campbell K.P.: Subunit identification and reconstitution of the N-type Ca2+ channel complex purified from brain. Science 261: 486–489, 1993.PubMedCrossRefGoogle Scholar
  8. 8.
    Roberts J., Snyder D.L., Aloyo V.J., Johnson M.D.: Decrease in norepinephrine (NE) release with age from cardiac adrenergic nerve terminals: role of calcium. Gerontohgist 32: (Special Issue II): 154, 1992 (abstract).Google Scholar
  9. 9.
    Daly R.N., Goldberg P.B., Roberts J.: Effects of age on neurotransmission at the cardiac sympathetic neuroeffector junction. J. Pharmacol. Exp. Ther. 245: 798–803, 1988.PubMedGoogle Scholar
  10. 10.
    Roberts J., Mortimer M.L., Ryan P.J., Johnson M.D., Turner N.: Role of calcium in adrenergic neurochemical transmission in the aging heart. J. Pharmacol. Exp. Ther. 253: 957–964, 1990.PubMedGoogle Scholar
  11. 11.
    Tumer N., Ryan P.J., Roberts J.: Action of potassium on neurochemical transmission at the cardiac adrenergic neuroeffector junction with aging. Mech. Ageing Dev. 52: 87–91, 1990.PubMedCrossRefGoogle Scholar
  12. 12.
    Tumer N., Mortimer M.L., Roberts J.: Gender differences in the effect of age on adrenergic neurotransmission in the heart. Exp. Gerontol. 27: 301–307, 1992.PubMedCrossRefGoogle Scholar
  13. 13.
    Bradford M.M.: A rapid and sensitive method for the quantitation of microform quantities of protein utilizing a principle of protein-dye binding. Anal. Biochem. 72: 248–254, 1976.PubMedCrossRefGoogle Scholar
  14. 14.
    Winer B.J.: Statistical Principals in Experimental Design. McGraw-Hill, New York, 1971.Google Scholar
  15. 15.
    Tallarida R.J., Murry R.B.: Manual of Pharmacologie Calculations with Computer Programs. Springer-Verlag, New York, 1986.CrossRefGoogle Scholar
  16. 16.
    Reimann W., Kollhofer U.: Voltage-sensitive Ca2+ channels in rat brain neocortical noradrenergic nerve terminals. Pharmacology 36: 249–257, 1988.PubMedCrossRefGoogle Scholar
  17. 17.
    Hirning L.D., Fox A.P., McCleskey E.W., Olivera B.M., Thayer S.A., Miller R.J., Tsien R.W.: Dominant role of N-type Ca2+ channels in evoked release of norepinephrine form sympathetic neurons. Science 239: 57–61, 1988.PubMedCrossRefGoogle Scholar
  18. 18.
    Tsien R.W., Lipscombe D., Madison D.V., Bley K.R., Fox A.P.: Multiple types of neuronal calcium channels and their selective modulation. TINS 11: 431–438, 1988.PubMedGoogle Scholar
  19. 19.
    Hofmann F., Habermann E.: Role of ω-conotoxin-sensitive calcium channels in inositolphosphate production and noradrenaline release due to potassium depolarization or stimulation with carbachol. Nauyn-Schmiedeberg’s Arch. Pharmacol. 341: 200–205, 1990.Google Scholar
  20. 20.
    Suszkiw J.B., Murawsky M.M., Former R.C.: Heterogeneity of presynaptic calcium channels revealed by species differences in the sensitivity of synaptosomal 45Ca entry to ω-conotoxin. Biochem. Biophys. Res. Commun. 145: 1283–1286, 1987.PubMedCrossRefGoogle Scholar
  21. 21.
    Gary W.R., Olivera B.M., Cruz L.J.: Peptide toxins from venomous conus snails. Ann. Rev. Biochem. 57: 665–700, 1988.CrossRefGoogle Scholar
  22. 22.
    Glossman H., Striessnig J.: Molecular properties of calcium channels. Rev. Physiol. Biochem. Pharmacol. 114: 1–105, 1990.CrossRefGoogle Scholar
  23. 23.
    Sihra T.S., Nichols R.A.: Mechanisms in the regulation of neurotransmitter release from brain nerve terminals: current hypotheses. Neurochem. Res. 18: 47–58, 1993.PubMedCrossRefGoogle Scholar
  24. 24.
    World Health Organization: World Health Statistics Annual: Vital Statistics and Causes of Death. World Health Organization, Geneva, 1986.Google Scholar
  25. 25.
    Eaker E.D., Packard B., Thom T.J.: Epidemiology and risk factors for coronary heart disease in women. Cardiovasc. Clin. 19: 129–145, 1989.PubMedGoogle Scholar
  26. 26.
    Kannel W.B., Hgortland M.C., McNamara P.M.: Menopause and risk of cardiovascular disease: the Framingham study. Ann. Intern. Med. 85: 447–452, 1976.PubMedCrossRefGoogle Scholar
  27. 27.
    Stampfer M.J., Coldiz G.A., Willett W.C., Manson J.E., Rosner B., Speizer F.E., Hennekens C.H.: Postmenopausal estrogen therapy and cardiovascular disease. N. Engl. J. Med. 325: 756–762, 1991.PubMedCrossRefGoogle Scholar
  28. 28.
    Nabulsi A.A., Folsom A.R., White A., Patsch W., Heiss G., Wu K.K., Szklo M.: Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. N. Engl. J. Med. 328: 1069–1074, 1993.PubMedCrossRefGoogle Scholar
  29. 29.
    Eysmann S.B., Douglas P.S.: Reperfusion and revascularization strategies for coronary artery disease in women. JAMA 268: 1903–1907, 1992.PubMedCrossRefGoogle Scholar
  30. 30.
    Barrett-Connor E., Bush T.L.: Estrogen and coronary heart disease in women. JAMA 265: 1861–1867, 1991.PubMedCrossRefGoogle Scholar
  31. 31.
    Claustre J., Peyrin L., Fitoussi R., Mornex R.: Sex differences in the adrenergic response to hypoglycemic stress in humans. Psychopharm. 67: 147–153, 1980.CrossRefGoogle Scholar
  32. 32.
    Storm D., Metzger B., Thrien B.: Effects of age on autonomic cardiovascular responsiveness in healthy men and women. Nursing Res. 38: 326–330, 1989.CrossRefGoogle Scholar
  33. 33.
    Fan T.M., Banerjee S.P.: Age-related reduction of beta-adrenoceptor sensitivity in rat heart occurs by multiple mechanisms. Gerontology 31: 373–380, 1985.PubMedCrossRefGoogle Scholar
  34. 34.
    Dakai M., Danziger R.S., Staddon J.M., Lakatta E.G., Hansford R.G.: Decrease with senescence in the norepinephrine-induced phosphorylation of myofilament proteins in isolated rat cardiac myocytes. J. Mol. Cell. Cardiol. 21: 1327–1336, 1989.CrossRefGoogle Scholar
  35. 35.
    O’Connor S.W., Scarpace P.J., Abrass I.B.: Age-associated decrease of adenylate cyclase activity in rat myocardium. Mech. Ageing Dev. 16: 91–95, 1981.PubMedCrossRefGoogle Scholar
  36. 36.
    Scarpace P.J., Abrass I.B.: Beta-adrenergic agonist-mediated desensitization in senescent rats. Mech. Ageing Dev. 35: 255–264, 1989.CrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 1995

Authors and Affiliations

  • David L. Snyder
    • 1
  • M. D. Johnson
    • 1
  • B. A. Eskin
    • 1
  • W. Wang
    • 1
  • J. Roberts
    • 1
  1. 1.Department of PharmacologyMedical College of PennsylvaniaPhiladelphiaUSA

Personalised recommendations