Skip to main content
Log in

Selective noradrenergic denervation of the heart following intravenous injections of vinblastine or vincristine

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    The progressive effects of a single injection (3 mg/kg i.v.) of either vinblastine or vincristine on the innervation of the rat atria have been examined.

  2. 2.

    Functional studies were performed by stimulating electrically the noradrenergic or cholinergic nerve fibres within isolated left atria from treated and control rats. In addition, the effects of the drugs on the ultrastructure of both types of nerve fibre were examined. The noradrenergic innervation was further examined by fluorescence histochemistry and measurement of the noradrenaline content of the atria.

  3. 3.

    On the basis of these studies it appeared that both drugs caused degeneration of noradrenergic nerves; cholinergic nerves seemed to be unaffected. Marked effects were seen 48 h after vinblastine treatment or 30 h after vincristine treatment.

  4. 4.

    Evidence is presented and discussed as to whether or not this action of the vinca alkaloids can be ascribed to their well-established effects on microtubules and intra-axonal transport processes.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Banks, P., Mayor, D., Mitchell, M., Tomlinson, D.: Studies on the translocation of noradrenaline-containing vesicles in postganglionic sympathetic neurones in vitro. Inhibition of movement by colchicine and vinblastine and evidence for the involvement of axonal microtubules. J. Physiol. (Lond.) 216, 625–639 (1971)

    Google Scholar 

  • Bennett, T., Cobb, J. L. S., Malmfors, T.: Fluorescence histochemical and ultrastructural observations on the effects of intravenous injections of vinblastine on noradrenergic nerves. Z. Zellforsch. 141, 517–527 (1973)

    Google Scholar 

  • Bennett, T., Gardiner, S. M.: The effects of intravenous injections of vinblastine or vincristine on the responses of the rat heart to nerve stimulation and to drugs. Brit. J. Pharmacol. Chemother. 53, 444P (1975)

  • Blinks, J. R.: Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle. J. Pharmacol. exp. Ther. 151, 221–235 (1966)

    Google Scholar 

  • Bolton, T. B.: Intramural nerves in the ventricular myocardium of the domestic fowl and other animals. Brit. J. Pharmacol. Chemother. 31, 253–268 (1967)

    Google Scholar 

  • Ceccarelli, B., Pensa, P.: Morphological aspects of synaptic vesicles after different aldehyde fixations. Proc. 4th Eur. Regional Conf. on EM, 2, 545–546 (1968)

    Google Scholar 

  • Cheney, D. L., Hanin, I., Massarelli, R., Trabucchi, M., Costa, E.: Vinblastine and vincristine: a study of their action on tissue concentrations of epinephrine, norepinephrine and acetylcholine. Neuropharmacology 12, 233–238 (1973)

    Google Scholar 

  • Häggendal, J.: An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissue. Acta physiol. scand. 59, 242–254 (1963)

    Google Scholar 

  • Hanbauer, I., Jacobowitz, D. M., Kopin, I. J.: Effect of vinblastine on noradrenergic axons. Brit. J. Pharmacol. 50, 219–225 (1974)

    Google Scholar 

  • Hanbauer, I., Kopin, I. J., Maengwyn-Davies, G. D., Thoa, N. B., Weise, V. K.: Effects of vinblastine on catecholamine-biosynthetic enzymes in heart, sympathetic ganglion and adrenal glands of rats. Brit. J. Pharmacol. 48, 106–112 (1973)

    Google Scholar 

  • Iversen, L. L.: The uptake and storage of noradrenaline in sympathetic nerves. Cambridge: University Press 1967

    Google Scholar 

  • Kapeller, K., Mayor, D.: An electron microscopic study of the early changes distal to a constriction in sympathetic nerves. Proc. roy. Soc. B 172, 53–63 (1969)

    Google Scholar 

  • Keen, P., Livingston, A.: Decline of tissue noradrenaline under the influence of a mitotic inhibitor. Nature New Biol. 227, 967–968 (1970)

    Google Scholar 

  • Keen, P., Livingston, A.: Intraneuronal transport of noradrenaline in the rat. Mem. Soc. Endocrinol. 19, 671–679 (1971)

    Google Scholar 

  • Reynolds, E. S.: The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J. Cell Biol. 17, 208–212 (1963)

    Google Scholar 

  • Tomlinson, D. R.: Two populations of granular vesicles in constricted postganglionic sympathetic nerves. J. Physiol. (Lond.) 245, 727–735 (1975)

    Google Scholar 

  • Tranzer, J. P., Thoenen, H.: Ultramorphologische Veränderungen der sympathetischen Nervenendigungen der Katze nach Vorbehandlung mit 5-und 6-Hydroxy-dopamin. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 257, 343–356 (1967)

    Google Scholar 

  • Valori, C., Brunori, C. A., Renzini, V., Corea, L.: Improved procedure for formation of epinephrine and norepinephrine fluophors by the trihydroxyindole reaction. Analyt. Biochem. 33, 158–167 (1970)

    Google Scholar 

  • Woods, R. I.: Acrylic aldehyde in sodium dichromate as a fixative for identifying catecholamine storage sites with the electron microscope. J. Physiol. (Lond.) 203, 35 P (1970)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bennett, T., Gardiner, S.M. & Tomlinson, D.R. Selective noradrenergic denervation of the heart following intravenous injections of vinblastine or vincristine. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 175–182 (1976). https://doi.org/10.1007/BF00499224

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00499224

Key words

Navigation