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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1973 May;48(1):59–72. doi: 10.1111/j.1476-5381.1973.tb08222.x

Rapid recovery of vascular adrenergic nerves in the rat after chemical sympathectomy with 6-hydroxydopamine

L Finch, G Haeusler, H Kuhn, H Thoenen
PMCID: PMC1776112  PMID: 4724194

Abstract

1. Twenty-four hours after the last of 4 intravenous doses of 6-hydroxydopamine (2×50 mg/kg on day 1 and 2×100 mg/kg on day 7) a complete impairment of adrenergic nerve function was observed in various organs of the rat.

2. A complete recovery of adrenergic nerve function in vascular smooth muscle was observed 7 days after the last dose of 6-hydroxydopamine whilst in non-vascular smooth muscle recovery took between 14 and 21 days.

3. On day 8, noradrenaline depletion produced by 6-hydroxydopamine was not as great in vascular tissues, such as the mesentery and renal artery, as in other tissues, such as the heart and salivary glands. Noradrenaline concentrations recovered much more rapidly in vascular than in other tissues.

4. Electron microscope studies of small mesenteric arteries showed a complete destruction of adrenergic nerve terminals 24 h after 6-hydroxydopamine (2×100 mg/kg). However, there was a reappearance of growing terminals within 7 days and after 28 days the regrowth of adrenergic nerve terminals seemed complete.

5. From the morphological and functional data it is concluded that 6-hydroxydopamine does produce complete destruction of vascular adrenergic nerve terminals. However, these terminals regenerate more rapidly than those in other tissues. This could explain the failure of intravenously administered 6-hydroxydopamine to prevent the development of experimental hypertension in the rat.

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Selected References

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  1. Ayitey-Smith E., Varma D. R. An assessment of the role of the sympathetic nervous system in experimental hypertension using normal and immunosympathectomized rats. Br J Pharmacol. 1970 Oct;40(2):175–185. doi: 10.1111/j.1476-5381.1970.tb09911.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berkowitz B. A., Spector S., Tarver J. H. Resistance of noradrenaline in blood vessels to depletion by 6-hydroxydopamine or immunosympathectomy. Br J Pharmacol. 1972 Jan;44(1):10–16. doi: 10.1111/j.1476-5381.1972.tb07233.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark D. W. Effects of immunosympathectomy on development of high blood pressure in genetically hypertensive rats. Circ Res. 1971 Mar;28(3):330–336. doi: 10.1161/01.res.28.3.330. [DOI] [PubMed] [Google Scholar]
  4. Clark D. W., Laverty R., Phelan E. L. Long-lasting peripheral and central effects of 6-hydroxydopamine in rats. Br J Pharmacol. 1972 Feb;44(2):233–243. doi: 10.1111/j.1476-5381.1972.tb07259.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clarke D. E., Smookler H. H., Barry H., 3rd Sympathetic nerve function and DOCA-NaCl induced hypertension. Life Sci I. 1970 Oct 1;9(19):1097–1108. doi: 10.1016/0024-3205(70)90141-4. [DOI] [PubMed] [Google Scholar]
  6. Drew G. M., Leach G. D. Corticosteroids and their effects on cardiovascular sensitivity in the pithed adrenalectomized rat. Arch Int Pharmacodyn Ther. 1971 Jun;191(2):255–260. [PubMed] [Google Scholar]
  7. Finch L., Leach G. D. A comparison of the effects of 6-hydroxydopamine immunosympathectomy and reserpine on the cardiovascular reactivity in the rat. J Pharm Pharmacol. 1970 May;22(5):354–360. doi: 10.1111/j.2042-7158.1970.tb08537.x. [DOI] [PubMed] [Google Scholar]
  8. Finch L., Leach G. D. Effects of 6-hydroxydopamine on the perfused rat mesentery preparation. J Pharm Pharmacol. 1970 Jul;22(7):543–544. doi: 10.1111/j.2042-7158.1970.tb10565.x. [DOI] [PubMed] [Google Scholar]
  9. Finch L., Leach G. D. The contribution of the sympathetic nervous system to the development and maintenance of experimental hypertension in the rat. Br J Pharmacol. 1970 Jun;39(2):317–324. doi: 10.1111/j.1476-5381.1970.tb12895.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Finch L., Leach G. D. The role of the sympathetic nervous system in the cardiovascular responses to angiotensin in the pithed rat. Br J Pharmacol. 1969 Jul;36(3):481–488. doi: 10.1111/j.1476-5381.1969.tb08004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gillespie J. S., Muir T. C. A method of stimulating the complete sympathetic outflow from the spinal cord to blood vessels in the pithed rat. Br J Pharmacol Chemother. 1967 May;30(1):78–87. doi: 10.1111/j.1476-5381.1967.tb02114.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haeusler G., Haefely W., Thoenen H. Chemical sympathectomy of the cat with 6-hydroxydopamine. J Pharmacol Exp Ther. 1969 Nov;170(1):50–61. [PubMed] [Google Scholar]
  13. LAVERTY R., SHARMAN D. F., VOGT M. ACTION OF 2, 4, 5-TRIHYDROXYPHENYLETHYLAMINE ON THE STORAGE AND RELEASE OF NORADRENALINE. Br J Pharmacol Chemother. 1965 Apr;24:549–560. doi: 10.1111/j.1476-5381.1965.tb01745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. OKAMOTO K., AOKI K. Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 1963 Mar;27:282–293. doi: 10.1253/jcj.27.282. [DOI] [PubMed] [Google Scholar]
  15. PORTER C. C., TOTARO J. A., STONE C. A. Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J Pharmacol Exp Ther. 1963 Jun;140:308–316. [PubMed] [Google Scholar]
  16. Thoenen H., Tranzer J. P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-Hydroxydopamine. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;261(3):271–288. doi: 10.1007/BF00536990. [DOI] [PubMed] [Google Scholar]
  17. Tranzer J. P., Thoenen H. An electron microscopic study of selective, acute degeneration of sympathetic nerve terminals after administration of 6-hydroxydopamine. Experientia. 1968 Feb 15;24(2):155–156. doi: 10.1007/BF02146956. [DOI] [PubMed] [Google Scholar]
  18. Tranzer J. P., Thoenen H. Electronmicroscopic localization of 5-hydroxydopamine (3,4,5-trihydroxy-phenyl-ethylamine), a new 'false' sympathetic transmitter. Experientia. 1967 Sep 15;23(9):743–745. doi: 10.1007/BF02154151. [DOI] [PubMed] [Google Scholar]
  19. Yamori Y., Yamabe H., De Jong W., Lovenberg W., Sjoerdsma A. Effect of tissue norepinephrine depletion by 6-hydroxydopamine on blood pressure in spontaneously hypertensive rats. Eur J Pharmacol. 1972 Jan;17(1):135–140. doi: 10.1016/0014-2999(72)90279-8. [DOI] [PubMed] [Google Scholar]
  20. de Champlain J. Degeneration and regrowth of adrenergic nerve fibers in the rat peripheral tissues after 6-hydroxydopamine. Can J Physiol Pharmacol. 1971 Apr;49(4):345–355. doi: 10.1139/y71-038. [DOI] [PubMed] [Google Scholar]
  21. von EULER U., LISHAJKO F. Improved technique for the fluorimetric estimation of catecholamines. Acta Physiol Scand. 1961 Apr;51:348–355. doi: 10.1111/j.1748-1716.1961.tb02128.x. [DOI] [PubMed] [Google Scholar]

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