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Postocclusive cutaneous vasodilatation mediated by substance P

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Summary

  1. 1.

    The cutaneous vasodilation following arterial occulusion (“reactive hyperemia”) was studied in the rat hind paw. A peak increase in venous outflow of 200–250% was observed within 1 min after a 3 min occlusion period.

  2. 2.

    Chronic denervation as well as capsaicin pretreatment reduced the postocclusive cutaneous vasodilatation by more than 60% (P<0.01). This demonstrates that the reactive vasodilatation is of neurogenic origin and mediated by small diameter afferent fibres.

  3. 3.

    Reduction of the postocclusive cutaneous vasodilatation after histamine depletion by compound 48/80 indicates the involvement of histamine.

  4. 4.

    Among all neuropeptides known to occur in primary sensory neurones only substance P and vasoactive intestinal polypeptide cause vasodilatation when infused i.a. into the rat paw. In contrast to antidromic sensory nerve stimulation or i.a. substance P infusion, vasoactive intestinal polypeptide does not cause plasma extravasation. The vasodilator potency of vasoactive intestinal polypeptide is about 1/500 of substance P in the rat paw. Therefore only substance P is able to mimic the reactive vasodilatation.

  5. 5.

    It is concluded that the postocclusive cutaneous vasodilatation is caused mainly by the release of substance P from peripheral endings of small diameter nerve fibres. The “axon reflex”, also involving neurogenic vasodilatation, is assumed to be exerted by the same mechanism.

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References

  • Arvier PT, Chahl LA, Ladd RJ (1977) Modification by capsaicin and compound 48/80 of dye leakage induced by irritants in the rat. Br J Pharmacol 59:61–68

    Google Scholar 

  • Bayliss WM (1901) On the origin from the spinal cord of the vasodilator fibres of the hind limb, and on the nature of these fibres. J Physiol (Lond) 26:173–209

    Google Scholar 

  • Bill A, Stjernschantz J, Mandahl A, Brodin E, Nilsson G (1979) Substance P: release on trigeminal nerve stimulation, effects in the eye. Acta Physiol Scand 106:371–373

    Google Scholar 

  • Breslauer F (1919) Die Pathogenese der trophischen Gewebsschäden nach der Nervenverletzung. Dtsch Z Chir 150:50–81

    Google Scholar 

  • Brodin E, Gazelius B, Lundberg JM, Olgart L (1981) Substance P in trigeminal nerve endings: Occurrence and release. Acta Physiol Scand (in press)

  • Burnstock G (1977) Autonomic neuroeffector junctions-reflex vasodilatation of the skin. J Invest Dermatol 69:47–57

    Google Scholar 

  • Burnstock G (1978) An assessment of purinergic nerve involvement in vasodilatation. In: Vanhoutte PM, Leusen J (eds) Mechanisms of vasodilatation, S. Karger. Basel New York, pp. 278–284

    Google Scholar 

  • Chahl LA (1979) The effect of putative peptide neurotransmitters on cutaneous vascular permeability in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 309:159–163

    Google Scholar 

  • Chahl LA, Manley SW (1980) Inflammatory peptide in spinal cord: evidence that the mediator of antidromic vasodilatation is not substance P. Neurosci Lett 18:99–103

    Google Scholar 

  • Chan-Palay V, Palay SL (1977) Immunocytochemical identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord: light microscopic studies. Proc Natl Acad Sci USA 8:3597–3601

    Google Scholar 

  • Chapman LF, Goodell H (1964) The participation of the nervous system in the inflammatory reaction. Ann NY Acad Sci 116:990–1017

    Google Scholar 

  • Carraway R, Leeman SE (1973) The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem 248:6854–6861

    Google Scholar 

  • Celander O, Folkow B (1953a) The nature and the distribution of afferent fibres provided with the axon relfex arrangement. Acta Physiol Scand 29:359–370

    Google Scholar 

  • Celander O, Folkow B (1953b) The correlation between the stimulation frequency and the dilator response evoked by “antidromic” excitation of the thin afferent fibres in the dorsal roots. Acta Physiol Scand 29:371–376

    Google Scholar 

  • Cooper IS (1950) A neurologic evaluation of the cutaneous histamine reaction. J Clin Invest 29:465–469

    Google Scholar 

  • Cuello AC, DelFiacco M, Paxinos G (1978) The central and peripheral ends of the substance P-containing sensory neurones in the rat trigeminal system. Brain Res 152:499–509

    Google Scholar 

  • Duling BR (1978) Oxygen, carbon dioxide, and hydrogen ion as local factors causing vasodilatation. In: Vankoutte PM, Leusen J (eds) Mechanisms of vasodilatation, S Karger, Basel New York, pp 193–199

    Google Scholar 

  • Frumin MJ, Ngai SH, Wang SC (1953) Evaluation of vasodilator mechanisms in the canine hind leg; question of dorsal root participation. Am J Physiol 173:428–436

    Google Scholar 

  • Gamse R, Holzer P, Lembeck F (1980a) Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin. Br J Pharmacol 68:207–213

    Google Scholar 

  • Gamse R, Leeman SE, Holzer P, Lembeck F (1980b) Effect of capsaicin on the content of somatostatin, substance P and neurotensin in the central and peripheral nervous system of the rat. In: Brzin M, Sket D, Bachelard H (eds) Synaptic constitutents in health and disease, Mladinska knjiga-Pergamon Press, Yugoslavia, Ljubljana, p 275

    Google Scholar 

  • Gazelius B, Olgart L (1980) Vasodilatation in the dental pulp produced by electrical stimulation of the inferior alveolar nerve in the cat. Acta Physiol Scand 108:181–186

    Google Scholar 

  • Hökfelt T, Elde R, Johansson O, Luft R, Nilsson G, Arimura A (1976) Immunohistochemical evidence for separate populations of somatostatin-containing and substance P-containing primary afferent neurons in the rat. Neuroscience 1:131–136

    Google Scholar 

  • Hökfelt T, Kellerth IO, Nilsson G, Pernow B (1975) Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res 100:235–252

    Google Scholar 

  • Holzer P, Jurna J, Gamse R, Lembeck F (1979) Nociceptive threshold after neonatal capsaicin treatment. Eur J Pharmacol 58:511–514

    Google Scholar 

  • Jancsó G, Király E, Jancsó-Gábor A (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature 270:741–743

    Google Scholar 

  • Jancsó G, Király E, Jancsó-Gábor A (1980) Chemosensitive pain fibres and inflammation. Int J Tiss Reac II, 57–66

    Google Scholar 

  • Jancsó N, Jancsó-Gábor A, Szolcsányi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother 31:138–151

    Google Scholar 

  • Johnson AR, Erdös EG (1973) Release of histamine from mast cells by vasoactive peptides. Proc Soc Exp Biol Med 142:1253–1256

    Google Scholar 

  • Juan H, Lembeck F (1974) Action of peptides and other algesic agents on paravascular pain receptors of the isolated perfused rabbit ear. Naunyn-Schmiedeberg's Arch Pharmacol 283:151–164

    Google Scholar 

  • Juan H, Sametz W (1980) Histamine-induced release of arachidonic and of prostaglandins in the peripheral vascular bed: Mode of action. Naunyn-Schmiedeberg's Arch Pharmacol 314:183–190

    Google Scholar 

  • Kiernan JA (1972) The involvement of mast cells in vasodilatation due to axon reflexes in injured skin. Quart J Exp Physiol 57:311–317

    Google Scholar 

  • Kiernan JA (1976) Evidence for the involvement of vasoactive constituents of mast cells in axon reflex vasodilatation in the skin of the rat. Derm Res 255:1–8

    Google Scholar 

  • Lembeck F, Holzer P (1979) Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn-Schmiedeberg's Arch Pharmacol 310:175–183

    Google Scholar 

  • Lembeck F, Starke K (1963) Substance P content and effect of capillary permeability of extract of various parts of human brain. Nature 199:1295–1296

    Google Scholar 

  • Lembeck F, Gamse R, Juan H (1977) Substance P and sensory nerve endings. In: von Euler US, Pernow B (eds) Substance P, Raven Press, New York, pp 169–181

    Google Scholar 

  • Lewis T, Marvin HM (1927) Observations relating to vasodilatation arising from antidromic impulses, to Herpes Zoster and trophic effects. Heart 14:27–46

    Google Scholar 

  • Lundberg JM, Hökfelt T, Nilsson G, Terenius L, Rehfeld J, Elde R, Said S (1978) Peptide neurons in the vagus, splanchnic and sciatic nerves. Acta Physiol Scand 104:499–501

    Google Scholar 

  • Olgart L, Hökfelt T, Nilsson G, Pernow B (1977a) Localisation of substance P-like immunoreactivity in nerves in the tooth pulp. Pain 4:153–159

    Google Scholar 

  • Olgart L, Gazelius B, Brodin E, Nilsson G (1977b) Release of substance P-like immunoreactivity from the dental pulp. Acta Physiol Scand 101:510–512

    Google Scholar 

  • Patterson GC (1956) Role of extra vascular pressure in the causation of reactive hyperemia in the human forearm. Clin Sci 15:17–25

    Google Scholar 

  • Raulino-Filho M, Garcia Leme J (1977) Participation of sensory nervous structures in the development of inflammatory reactions. Br J Exp Pathol 58:124–129

    Google Scholar 

  • Reed WB, Pidgeon J, Becker SW (1961) Studies on the triple response of Lewis in patients with spinal cord injury. J Invest Dermatol 37:135–143

    Google Scholar 

  • Rehfeld JF, Goltermann N, Larsson LI, Emson PM, Lee CM (1979) Gastrin and cholecystokinin in central and peripheral neurons. Fed Proc 38:2325–2329

    Google Scholar 

  • Rosell S, Olgart L, Gazelius B, Panopoulos P, Folkers K, Hörig J (1981) Inhibition of antidromic and substance P-induced vasodilatation by a substance P antagonist. Acta Physiol Scand (in press)

  • Scadding JW (1980) The permanent anatomical effects of neonatal capsaicin on somatosensory nerves. J Anat 131:473–484

    Google Scholar 

  • Seybold V, Elde R (1980) Immunohistochemical studies of peptidergic neurons in the dorsal horn of the spinal cord. J Histochem Cytochem 28:367–370

    Google Scholar 

  • Sonnenschein RR, Bernstein M (1957) Relation to the central nervous system of neural pathways mediating histamine flare and nicotine sweating. J Appl Physiol 11:481–485

    Google Scholar 

  • Stach W (1961) Morphologische Beziehungen zwischen Mastzellen und vegetativer Endformation. Zeitschr Mikr Anat Forschung 67:257–280

    Google Scholar 

  • Starke K (1964) Substanz P-Gehalt und permeabilitätserhöhende Wirkung in verschiedenen Gehirngebieten. Naunyn-Schmiedeberg's Arch Exp Path u Pharmak 247:149–163

    Google Scholar 

  • Vanhoutte PM, Leusen I (1978) Mechanism of vasodilatation Karger, Basel New York

    Google Scholar 

  • Willems JL, Bogaert MG (1978) Neurogenic vasodilatation. Gen Pharmacol 9:223–227

    Google Scholar 

Download references

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Authors and Affiliations

  1. Pain Research Commission of the Austrian Academy of Sciences and Institute of Experimental and Clinical Pharmacology of the University of Graz, Universitätsplatz 4, A-8010, Graz, Austria

    Fred Lembeck & Josef Donnerer

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  1. Fred Lembeck
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  2. Josef Donnerer
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Lembeck, F., Donnerer, J. Postocclusive cutaneous vasodilatation mediated by substance P. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 165–171 (1981). https://doi.org/10.1007/BF00505312

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  • DOI: https://doi.org/10.1007/BF00505312

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