Pflügers Archiv

, Volume 413, Issue 5, pp 451–455 | Cite as

Sodium salicylate: alternate mechanism of central antipyretic action in the rat

  • Susan J. Alexander
  • Keith E. Cooper
  • Warren L. Veale
Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology


Infusion of sodium salicylate (50.0 or 100.0 μg/μl) into the ventral septal area (VSA) of the rat brain suppressed Prostaglandin-E1-induced hyperthermia. Infusion of artificial cerebrospinal fluid (aCSF) or 10.0 μg doses of salicylate did not. The suppression of intracerebroventricularly-induced (icv) Prostaglandin E1 (PGE1) hyperthermia was not due to a hypothermic action of salicylate since salicylate infusions given during cold exposure (10.0°C) did not lower core body temperatures. A possible interaction between salicylate and endogenous arginine vasopressin (AVP) was investigated. Infusion of both salicylate (50.0 μg/μl) and either AVP antiserum or AVP antagonist into the VSA resulted in PGE hyperthermias occurring at levels which were not different from control levels as opposed to enhanced hyperthermia (antiserum or antagonist alone) or suppressed hyperthermia (salicylate alone). These results are consistent with the notion that sodium salicylate infusions within the VSA enhance AVP action and thus bring about the attenuation of PGE-induced hyperthermia.

Key words

Sodium salicylate Arginine vasopressin Fever Prostaglandin E Central nervous system ventral septal area Hyperthermia 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Albers HE, Pollock J, Simmons WH, Ferris CF (1986) A V1-like receptor mediates vasopressin-induced flank marking behavior in hamster hypothalamus. J Neurosci 6:2085–2089Google Scholar
  2. 2.
    Alexander SJ, Cooper KE, Veale WL (1987) Blockade of prosta-glandin E1 hyperthermia by sodium salicylate given into the ventral septal area of the rat brain. J Physiol 384:223–231Google Scholar
  3. 3.
    Buijs RM (1978) Intra- and extrahypothalamic vasopressin and oxytocin pathway in the rat. Cell Tissue Res 192:423–436Google Scholar
  4. 4.
    Buijs RM, Heerikhuize JJ (1982) Vasopressin and oxytocin release in the brain — a synaptic event. Brain Res 252:71–76Google Scholar
  5. 5.
    Clark WG (1980) Antipyretic: mechanisms of action. In: Lipton JM (ed) Fever. Raven Press, New York, pp 131–140Google Scholar
  6. 6.
    Clark WG, Cumby HR (1975) The antipyretic effect of indomethacin. J Physiol 248:625–638Google Scholar
  7. 7.
    Cooper KE, Kasting NW, Lederis K, Veale WL (1979) Evidence supporting a role for endogenous vasopressin in natural suppression of fever in the sheep. J Physiol 295:33–45Google Scholar
  8. 8.
    Cooper KE, Naylor AM, Veale WL (1987) Evidence supporting a role for endogenous vasopressin in fever suppression in the rat. J Physiol 387:163–172Google Scholar
  9. 9.
    Cranston WI, Rawlins MD (1972) Effects of intracerebral microinjection of sodium salicylate on temperature regulation in the rabbit. J Physiol 222:257–266Google Scholar
  10. 10.
    De Vries GJ, Buijs RM, Van Leeuwen FW, Caffe AR, Swaab DF (1985) The vasopressinergic innervation of the brain in normal and castrated rats. J Comp Neurol 233:236–254Google Scholar
  11. 11.
    Disturnal JE, Veale WL, Pittman QJ (1986) The ventral septal area: electrophysiological evidence for a possible role in antipyresis. Neuroscience 19:795–802Google Scholar
  12. 12.
    Grundmann MJ (1969) Studies on the action of antipyretic substances. PhD Thesis, University of Oxford, OxfordGoogle Scholar
  13. 13.
    Hori T, Nakashima T, Kiyohara T, Shibata M (1984) Effects of leukocytic pyrogen and sodium salicylate on hypothalamic neurons in vitro. Neurosci Lett 49:313–318Google Scholar
  14. 14.
    Kasting NW (1980) An antipyretic system in the brain and the role of vasopressin. PhD Thesis, University of Calgary, CalgaryGoogle Scholar
  15. 15.
    Kruszynski M, Lammek B, Manning M, Seto J, Haldar J, Sawyer WH (1980) [1-(β-mercapto-β,β-cyclopentamethylene-propionic acid)-2-(O-methyl)tyrosine] arginine vasopressin and [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid] arginine vasopressin, two highly potent antagonists of the vasopressor response to arginine vasopressin. J Med Chem 23:364–368Google Scholar
  16. 16.
    Malkinson TJ, Bridges TE, Veale WL, Lederis K, Ko D (1987) Enhancement of endotoxin fever with push-pull perfusion of the septum with vasopressin antiserum. Proceedings of Satellite Symposium “Thermal Physiology” 8:A6Google Scholar
  17. 17.
    Merker G, Blahser S, Ziesberger E (1980) Reactivity pattern of vasopressin-containing neurons and its relation to the antipyretic reaction in the pregnant guinea pig. Cell Tissue Res 212: 47–61Google Scholar
  18. 18.
    Milton AS, Wendlandt S (1971) Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol 218:325–336Google Scholar
  19. 19.
    Mo N, Ammari R, Dun NJ (1985) Prostaglandin inhibits Ca2+-dependent potentials in mammalian sympathetic neurons. Brain Research 334:325–329Google Scholar
  20. 20.
    Moore G, Lutterodt A, Burford G, Lederis K (1977) A highly specific antiserum for arginine vasopressin. Endocrinology 101:1421–1435Google Scholar
  21. 21.
    Nakashima T, Hori T, Kiyohara T, Shibata M (1985) Effect of endotoxin and sodium salicylate on preoptic thermosensitive neurons in tissue slices. Brain Res Bull 15:459–463Google Scholar
  22. 22.
    Naylor AM, Ruwe WD, Burnard DM, McNeeley PD, Turner SL, Pittman QJ, Veale WL (1985) Vasopressin-induced motor disturbances: Localization of a sensitive forebrain site in the rat. Brain Res 361:242–246Google Scholar
  23. 23.
    Naylor AM, Ruwe WD, Veale WL (1986) Thermoregulatory actions of centrally administered vasopressin in the rat. Neuropharmacology 25:787–794Google Scholar
  24. 24.
    Ojeda SR, Negro-Vilar A (1984) Release of PGE2 from the hypothalamus depends on extracellular Ca2+ availability: relation to LHRH release. Endocrinology 39:442–447Google Scholar
  25. 25.
    Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, New York, LondonGoogle Scholar
  26. 26.
    Polk DL, Lipton JM (1975) Effects of sodium salicylate, aminopyrine and chlorpromazine on behavioral temperature regulation. Pharmacol Biochem Behav 3:167–172Google Scholar
  27. 27.
    Poulin P, Lederis K, Pittman QJ (1988) Subcellular localization and characterization of vasopressin binding sites in the ventral septal area, lateral septum, and hippocampus of the rat brain. J Neurochem 50:889–898Google Scholar
  28. 28.
    Ruwe WD, Naylor AM, Veale WL (1985) Perfusion of vasopressin within the rat brain suppresses prostaglandin E-hyperthermia. Brain Res 338:219–224Google Scholar
  29. 29.
    Satinoff E (1972) Salicylate: action on normal body temperature in rats. Science 176:532–533Google Scholar
  30. 30.
    Schoener EP, Wang SC (1974) Sodium acetylsalicylate effectiveness against fever induced by leukocytic pyrogen and prostaglandin E1 in cat. Experientia 30:383–384Google Scholar
  31. 31.
    Segar WE, Holliday MA (1958) Physiologic abnormalities of salicylate intoxication. N Engl J Med 259:1191–1193Google Scholar
  32. 32.
    Thiessen JJ (1982) Pharmacokinetics of salicylates. In: Barnett HJM, Hirsh J, Fraser-Mustard J (eds) Acetylsalicylate acid: new uses for an old drug. Raven Press, New York, pp 49–62Google Scholar
  33. 33.
    Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 231:232–235Google Scholar
  34. 34.
    Veale WL, Cooper KE, Ruwe WD (1984) Vasopressin: Its role in antipyresis and febrile convulsion. Brain Res Bull 12(2): 161–165Google Scholar
  35. 35.
    Woolf CJ, Willies GH, Laburn H, Rosendorff C (1975) Pyrogen and prostaglandin fever in rabbit. I. Effects of salicylate and role of cyclic AMP. Neuropharmacology 14:397–403Google Scholar
  36. 36.
    Zeisberger E (1985) Role of vasopressin in fever regulation and suppression. TIPS 6:428–430Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Susan J. Alexander
    • 1
  • Keith E. Cooper
    • 1
  • Warren L. Veale
    • 1
  1. 1.Department of Medical Physiology, Faculty of MedicineThe University of CalgaryCalgaryCanada

Personalised recommendations