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. 1988 Dec;95(4):1101–1108. doi: 10.1111/j.1476-5381.1988.tb11744.x

Noradrenaline release evoked by a physiological irregular sympathetic discharge pattern is modulated by prejunctional alpha- and beta-adrenoceptors in vivo.

T Kahan 1, J Pernow 1, J Schwieler 1, B G Wallin 1, J M Lundberg 1, P Hjemdahl 1
PMCID: PMC1854281  PMID: 2851357

Abstract

1. Sympathetic nerve stimulation-evoked overflow of endogenous noradrenaline (NA) and vasoconstriction were studied in canine blood-perfused gracilis muscle in situ. Nerves were stimulated at an average frequency of 2 Hz (240 pulses, 120 s) with impulses derived from a recording of the normal irregular sympathetic discharge to human skeletal muscle, with regular bursts of impulses, or with the conventional continuous stimulus mode. 2. Variations in impulse activity were closely paralleled by changes in vascular tone. However, all stimulation patterns evoked the same integrated NA overflow and the same degree of vasoconstriction. 3. Blockade of beta-adrenoceptors by propranolol (0.5 mg kg-1 i.v.) significantly reduced NA overflow and vasoconstriction evoked both by continuous and irregular nerve stimulation, by approximately 15-20%. 4. The enhancement of NA overflow following alpha-adrenoceptor blockade by phenoxybenzamine (0.5 mg kg-1 local i.a.) was significantly greater when evoked by continuous than by irregular nerve discharge (24 vs 14 fold). Effects were similar with irregular and regular burst activity. Half of this enhancement has been shown to be due to blockade of neuronal uptake of NA by phenoxybenzamine. Vasoconstrictor responses to all stimulation patterns were similarly reduced, but not abolished, by phenoxybenzamine. 5. The normal irregular sympathetic discharge seems to evoke a similar integrated NA release and equally pronounced vasoconstriction as stimulation with regular bursts or at constant frequency. We provide additional evidence for a physiological prejunctional alpha-adrenoceptor-mediated inhibition of NA release. This mechanism may be influenced by the discharge pattern. Also prejunctional beta-adrenoceptors seem to modulate NA release under physiological conditions. However, the alpha-adrenoceptor-mediated mechanism is quantitatively more important.

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Selected References

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  1. Andersson P. O., Bloom S. R., Edwards A. V. Parotid responses to stimulation of the parasympathetic innervation in bursts in weaned lambs. J Physiol. 1982 Sep;330:163–174. doi: 10.1113/jphysiol.1982.sp014335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersson P. O., Bloom S. R., Järhult J. Colonic motor and vascular responses to pelvic nerve stimulation and their relation to local peptide release in the cat. J Physiol. 1983 Jan;334:293–307. doi: 10.1113/jphysiol.1983.sp014495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andersson P. O. Comparative vascular effects of stimulation continuously and in bursts of the sympathetic nerves to cat skeletal muscle. Acta Physiol Scand. 1983 Aug;118(4):343–348. doi: 10.1111/j.1748-1716.1983.tb07281.x. [DOI] [PubMed] [Google Scholar]
  4. Burnstock G., Kennedy C. A dual function for adenosine 5'-triphosphate in the regulation of vascular tone. Excitatory cotransmitter with noradrenaline from perivascular nerves and locally released inhibitory intravascular agent. Circ Res. 1986 Mar;58(3):319–330. doi: 10.1161/01.res.58.3.319. [DOI] [PubMed] [Google Scholar]
  5. Cousineau D., Goresky C. A., Bach G. G., Rose C. P. Effect of beta-adrenergic blockade on in vivo norepinephrine release in canine heart. Am J Physiol. 1984 Feb;246(2 Pt 2):H283–H292. doi: 10.1152/ajpheart.1984.246.2.H283. [DOI] [PubMed] [Google Scholar]
  6. Dahlöf C., Kahan T., Ablad B. Prejunctional beta 2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ. Acta Physiol Scand. 1987 Apr;129(4):499–503. doi: 10.1111/j.1748-1716.1987.tb08089.x. [DOI] [PubMed] [Google Scholar]
  7. Dahlöf C. Studies on beta-adrenoceptor mediated facilitation of sympathetic neurotransmission. Acta Physiol Scand Suppl. 1981;500:1–147. [PubMed] [Google Scholar]
  8. FOLKOW B. Impulse frequency in sympathetic vasomotor fibres correlated to the release and elimination of the transmitter. Acta Physiol Scand. 1952;25(1):49–76. doi: 10.1111/j.1748-1716.1952.tb00858.x. [DOI] [PubMed] [Google Scholar]
  9. Hjemdahl P. Catecholamine measurements in plasma by high-performance liquid chromatography with electrochemical detection. Methods Enzymol. 1987;142:521–534. doi: 10.1016/s0076-6879(87)42065-x. [DOI] [PubMed] [Google Scholar]
  10. Hjemdahl P., Daleskog M., Kahan T. Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979 Jul 9;25(2):131–138. doi: 10.1016/0024-3205(79)90384-9. [DOI] [PubMed] [Google Scholar]
  11. Kahan T., Dahlöf C., Hjemdahl P. Facilitation of nerve stimulation evoked noradrenaline overflow by isoprenaline but not by circulating adrenaline in the dog in vivo. Life Sci. 1987 May 4;40(18):1811–1818. doi: 10.1016/0024-3205(87)90092-0. [DOI] [PubMed] [Google Scholar]
  12. Kahan T., Dahlöf C., Hjemdahl P. Influence of acetylcholine, peptides, and other vasodilators on endogenous noradrenaline overflow and vasoconstriction in canine blood perfused gracilis muscle. Acta Physiol Scand. 1985 Jul;124(3):457–465. doi: 10.1111/j.1748-1716.1985.tb07682.x. [DOI] [PubMed] [Google Scholar]
  13. Kahan T., Dahlöf C., Hjemdahl P. Prejunctional alpha-adrenoceptor-mediated inhibition of norepinephrine release in blood-perfused skeletal muscle in situ. J Cardiovasc Pharmacol. 1987 May;9(5):555–562. doi: 10.1097/00005344-198705000-00009. [DOI] [PubMed] [Google Scholar]
  14. Kahan T., Hjemdahl P., Dahlöf C. Relationship between the overflow of endogenous and radiolabelled noradrenaline from canine blood perfused gracilis muscle. Acta Physiol Scand. 1984 Dec;122(4):571–582. doi: 10.1111/j.1748-1716.1984.tb07546.x. [DOI] [PubMed] [Google Scholar]
  15. Kahan T., Hjemdahl P. Pre- and postjunctional alpha-adrenoceptor-mediated effects of prazosin, methoxamine and 6-fluoronoradrenaline in blood-perfused canine skeletal muscle in situ. Eur J Pharmacol. 1987 Jan 6;133(1):9–20. doi: 10.1016/0014-2999(87)90200-7. [DOI] [PubMed] [Google Scholar]
  16. Kahan T., Hjemdahl P. Prejunctional beta 2-adrenoceptor-mediated enhancement of noradrenaline release in skeletal muscle vasculature in situ. J Cardiovasc Pharmacol. 1987 Oct;10(4):433–438. doi: 10.1097/00005344-198710000-00008. [DOI] [PubMed] [Google Scholar]
  17. Kahan T. Prejunctional adrenergic receptors and sympathetic neurotransmission: studies in canine skeletal muscle vasculature in situ. Acta Physiol Scand Suppl. 1987;560:1–38. [PubMed] [Google Scholar]
  18. Langer S. Z. Presynaptic regulation of the release of catecholamines. Pharmacol Rev. 1980 Dec;32(4):337–362. [PubMed] [Google Scholar]
  19. Lundberg J. M., Tatemoto K. Pancreatic polypeptide family (APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to alpha-adrenoceptor blockade. Acta Physiol Scand. 1982 Dec;116(4):393–402. doi: 10.1111/j.1748-1716.1982.tb07157.x. [DOI] [PubMed] [Google Scholar]
  20. Nilsson H., Ljung B., Sjöblom N., Wallin B. G. The influence of the sympathetic impulse pattern on contractile responses of rat mesenteric arteries and veins. Acta Physiol Scand. 1985 Mar;123(3):303–309. doi: 10.1111/j.1748-1716.1985.tb07592.x. [DOI] [PubMed] [Google Scholar]
  21. Pernow J., Kahan T., Hjemdahl P., Lundberg J. M. Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle. Acta Physiol Scand. 1988 Jan;132(1):43–50. doi: 10.1111/j.1748-1716.1988.tb08296.x. [DOI] [PubMed] [Google Scholar]
  22. Pernow J., Kahan T., Lundberg J. M. Neuropeptide Y and reserpine-resistant vasoconstriction evoked by sympathetic nerve stimulation in the dog skeletal muscle. Br J Pharmacol. 1988 Jul;94(3):952–960. doi: 10.1111/j.1476-5381.1988.tb11609.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schmidt H. H., Schurr C., Hedler L., Majewski H. Local modulation of noradrenaline release in vivo: presynaptic beta 2-adrenoceptors and endogenous adrenaline. J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):641–649. doi: 10.1097/00005344-198407000-00014. [DOI] [PubMed] [Google Scholar]
  24. Starke K. Presynaptic alpha-autoreceptors. Rev Physiol Biochem Pharmacol. 1987;107:73–146. [PubMed] [Google Scholar]
  25. Stj-5aarne L., Brundin J. Dual adreoceptor-mediated control of noradrenaline secretion from human vasoconstrictor nerves: facilitation by BETA-receptors and inhibitor by alpha-receptors. Acta Physiol Scand. 1975 May;94(1):139–141. doi: 10.1111/j.1748-1716.1975.tb05872.x. [DOI] [PubMed] [Google Scholar]
  26. Sundlöf G., Wallin B. G. The variability of muscle nerve sympathetic activity in resting recumbent man. J Physiol. 1977 Nov;272(2):383–397. doi: 10.1113/jphysiol.1977.sp012050. [DOI] [PMC free article] [PubMed] [Google Scholar]

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