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. 1996 Dec;119(7):1347–1354. doi: 10.1111/j.1476-5381.1996.tb16045.x

Effects of short- and long-term sympathectomy on vasoconstrictor responses of the rat mesenteric arterial bed.

V Ralevic 1, G Burnstock 1
PMCID: PMC1915809  PMID: 8968542

Abstract

1. The effects of short- and long-term sympathectomy were evaluated on vasoconstrictor function of constantly perfused mesenteric arterial beds isolated from rats: the effects of short-term sympathectomy were assessed at 3 and 8 days after 6-hydroxydopamine (6-OHDA) treatment of adult rats; the effects of long-term sympathectomy were assessed in adult rats treated at youth with guanethidine. 2. The relative degree of residual sympathetic innervation of the mesenteric arterial preparations was assessed by responses to electrical field stimulation (EFS; 16 Hz, 1 ms, 90 V, 30 s). Control responses were 95.6 +/- 3.9 mmHg (n = 35). Responses after sympathectomy were: 3 days after 6-OHDA, 2.9 +/- 0.9 mmHg (n = 15) < 8 days after 6-OHDA, 14.1 +/- 2.1 mmHg (n = 14) < guanethidine, 21.1 +/- 4.1 mmHg (n = 16). 3. Three days after 6-OHDA treatment there was an increase in the sensitivities of response to vasopressin and endothelin, producing leftward shifts of the dose-response curves of 0.66 +/- 0.11 and 0.88 +/- 0.13 log units respectively (n = 7-11), and a small increase in sensitivity of responses to noradrenaline (NA) and ATP. The maximal response to 5-hydroxytryptamine (5-HT) was increased. In contrast, there was a decrease in maximal constriction to NA and to the alpha 1-adrenoceptor agonist methoxamine. The alpha 2-adrenoceptor agonist clonidine did not elicit vasoconstriction at basal tone. There was no difference in vasodilator responses to the beta-adrenoceptor agonist isoprenaline in preparations with tone raised with prostaglandin F2 alpha (PGF2 alpha; 0.1-0.3 microM). 4. Eight days after 6-OHDA sympathectomy there was no significant difference in sensitivities or maximal responses to ATP, vasopressin and endothelin, but a small increase in the sensitivity of responses to 5-HT. Maximal responses to NA and methoxamine were significantly lower than the controls, but sensitivities were similar. There was no significant difference in vasodilator responses to isoprenaline in PGF2 alpha-raised tone preparations. 5. After long-term guanethidine sympathectomy maximal responses to 5-HT and NA were significantly reduced. Responses to ATP, vasopressin and endothelin were unchanged. 6. In mesenteric arterial preparations from untreated rats, ouabain (0.1 mM), a blocker of the Na+/K+ pump, significantly augmented the sensitivity and maximal responses to EFS, NA, methoxamine and 5-HT. Responses to ATP, vasopressin and endothelin were unaffected. 7. It is concluded that in the rat mesenteric arterial bed, short-term sympathectomy, where only 3% of the sympathetic nerve-mediated response remained, results in non-uniform changes in sensitivity and maximal responses to different vasoconstrictors, which cannot be entirely explained by changes in the Na+/K+ pump. Most of these changes disappeared at 8 days after 6-OHDA treatment, when nerve-mediated responses had partially returned. After long-term guanethidine sympathectomy, there was little change in responses to vasoconstrictors, and nerve-mediated responses were reduced to 22%. Although the variable factors are complex, it appears that in general, changes in responses of smooth muscle to vasoconstrictor substances after sympathetic denervation only occur if there is near-complete loss of nerve-mediated responses.

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Selected References

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  1. Abel P. W., Urquilla P. R., Goto K., Westfall D. P., Robinson R. L., Fleming W. W. Chronic reserpine treatment alters sensitivity and membrane potential of the rabbit saphenous artery. J Pharmacol Exp Ther. 1981 May;217(2):430–439. [PubMed] [Google Scholar]
  2. Aberdeen J., Corr L., Milner P., Lincoln J., Burnstock G. Marked increases in calcitonin gene-related peptide-containing nerves in the developing rat following long-term sympathectomy with guanethidine. Neuroscience. 1990;35(1):175–184. doi: 10.1016/0306-4522(90)90132-n. [DOI] [PubMed] [Google Scholar]
  3. Angus J. A., Cocks T. M. Endothelium-derived relaxing factor. Pharmacol Ther. 1989;41(1-2):303–352. doi: 10.1016/0163-7258(89)90112-5. [DOI] [PubMed] [Google Scholar]
  4. Aprigliano O., Hermsmeyer K. Trophic influence of the sympathetic nervous system on the rat portal vein. Circ Res. 1977 Aug;41(2):198–206. doi: 10.1161/01.res.41.2.198. [DOI] [PubMed] [Google Scholar]
  5. Bevan R. D. Effect of sympathetic denervation on smooth muscle cell proliferation in the growing rabbit ear artery. Circ Res. 1975 Jul;37(1):14–19. doi: 10.1161/01.res.37.1.14. [DOI] [PubMed] [Google Scholar]
  6. Bevan R. D. Influence of adrenergic innervation on vascular growth and mature characteristics. Am Rev Respir Dis. 1989 Nov;140(5):1478–1482. doi: 10.1164/ajrccm/140.5.1478. [DOI] [PubMed] [Google Scholar]
  7. Bevan R. D., Tsuru H. Functional and structural changes in the rabbit ear artery after sympathetic denervation. Circ Res. 1981 Aug;49(2):478–485. doi: 10.1161/01.res.49.2.478. [DOI] [PubMed] [Google Scholar]
  8. Carrier O., Jr, Hester R. K. The relationship between calcium and increased sensitivity of rabbit aortae four hours after reserpine. Br J Pharmacol. 1976 Apr;56(4):449–455. doi: 10.1111/j.1476-5381.1976.tb07457.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Colucci W. S., Gimbrone M. A., Jr, Alexander R. W. Regulation of the postsynaptic alpha-adrenergic receptor in rat mesenteric artery. Effects of chemical sympathectomy and epinephrine treatment. Circ Res. 1981 Jan;48(1):104–111. doi: 10.1161/01.res.48.1.104. [DOI] [PubMed] [Google Scholar]
  10. Fleming W. W. Membrane potential and vascular smooth muscle sensitivity. A minireview. Blood Vessels. 1987;24(3):108–112. doi: 10.1159/000158680. [DOI] [PubMed] [Google Scholar]
  11. Goto K., Westfall D. P., Fleming W. W. Denervation-induced changes in electrophysiologic parameters of the smooth muscle of the guinea-pig and rat was deferens. J Pharmacol Exp Ther. 1978 Feb;204(2):325–333. [PubMed] [Google Scholar]
  12. Graves J., Poston L. Beta-adrenoceptor agonist mediated relaxation of rat isolated resistance arteries: a role for the endothelium and nitric oxide. Br J Pharmacol. 1993 Mar;108(3):631–637. doi: 10.1111/j.1476-5381.1993.tb12853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heath J. W., Burnstock G. Selectivity of neuronal degeneration produced by chronic guanethidine treatment. J Neurocytol. 1977 Aug;6(4):397–405. doi: 10.1007/BF01178225. [DOI] [PubMed] [Google Scholar]
  14. Johnson E. M., Jr, O'Brien F., Werbitt R. Modification and characterization of the permanent sympathectomy produced by the administration of guanethidine to newborn rats. Eur J Pharmacol. 1976 May;37(1):45–54. doi: 10.1016/0014-2999(76)90006-6. [DOI] [PubMed] [Google Scholar]
  15. Lacroix J. S., Lundberg J. M. Adrenergic and neuropeptide Y supersensitivity in denervated nasal mucosa vasculature of the pig. Eur J Pharmacol. 1989 Oct 4;169(1):125–136. doi: 10.1016/0014-2999(89)90824-8. [DOI] [PubMed] [Google Scholar]
  16. Lee R. M., Borkowski K. R., Leenen F. H., Tsoporis J., Coughlin M. Combined effect of neonatal sympathectomy and adrenal demedullation on blood pressure and vascular changes in spontaneously hypertensive rats. Circ Res. 1991 Sep;69(3):714–721. doi: 10.1161/01.res.69.3.714. [DOI] [PubMed] [Google Scholar]
  17. Lee R. M., Triggle C. R., Cheung D. W., Coughlin M. D. Structural and functional consequence of neonatal sympathectomy on the blood vessels of spontaneously hypertensive rats. Hypertension. 1987 Sep;10(3):328–338. doi: 10.1161/01.hyp.10.3.328. [DOI] [PubMed] [Google Scholar]
  18. MCGREGOR D. D. THE EFFECT OF SYMPATHETIC NERVE STIMULATION OF VASOCONSTRICTOR RESPONSES IN PERFUSED MESENTERIC BLOOD VESSELS OF THE RAT. J Physiol. 1965 Mar;177:21–30. doi: 10.1113/jphysiol.1965.sp007572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nyborg N. C., Korsgaard N., Mulvany M. J. Neonatal sympathectomy of normotensive Wistar-Kyoto and spontaneously hypertensive rats with 6-hydroxydopamine: effects on resistance vessel structure and sensitivity to calcium. J Hypertens. 1986 Aug;4(4):455–461. doi: 10.1097/00004872-198608000-00010. [DOI] [PubMed] [Google Scholar]
  20. Pipili E. A study on the postjunctional excitatory alpha-adrenoreceptor subtypes in the mesenteric arterial bed of the rat. J Auton Pharmacol. 1986 Jun;6(2):125–132. doi: 10.1111/j.1474-8673.1986.tb00639.x. [DOI] [PubMed] [Google Scholar]
  21. Ralevic V., Rubino A., Burnstock G. Prejunctional modulation of sensory-motor nerve-mediated vasodilatation of the rat mesenteric arterial bed by opioid peptides. J Pharmacol Exp Ther. 1994 Feb;268(2):772–778. [PubMed] [Google Scholar]
  22. Sarmento A., Soares-da-Silva P., Teixeira A. A., Azevedo I. Effects of denervation induced by 6-hydroxydopamine on cell nucleus activity of arterial and cardiac cells of the dog. J Auton Pharmacol. 1987 Jun;7(2):119–126. doi: 10.1111/j.1474-8673.1987.tb00141.x. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Trendelenburg U., Maxwell R. A., Pluchino S. Methoxamine as a tool to assess the importance of intraneuronal uptake of l-norepinephrine in the cat's nictitating membrane. J Pharmacol Exp Ther. 1970 Mar;172(1):91–99. [PubMed] [Google Scholar]
  25. Trendelenburg U. Mechanisms of supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol Rev. 1966 Mar;18(1):629–640. [PubMed] [Google Scholar]
  26. Watanabe Y., Lai R. T., Maeda H., Yoshida H. Reserpine and sympathetic denervation cause an increase of postsynaptic alpha 2-adrenoceptors. Eur J Pharmacol. 1982 May 7;80(1):105–108. doi: 10.1016/0014-2999(82)90183-2. [DOI] [PubMed] [Google Scholar]
  27. Westfall D. P., Fedan J. S. The effect of pretreatment with 6-hydroxydopamine on the norepinephrine concentration and sensitivity of the rat vas deferens. Eur J Pharmacol. 1975 Sep-Oct;33(2):413–417. doi: 10.1016/0014-2999(75)90189-2. [DOI] [PubMed] [Google Scholar]

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