Agents and Actions

, Volume 22, Issue 3–4, pp 223–230 | Cite as

Effects of dietary poly-unsaturated fatty acids on tracheal histaminergic and cholinergic responsiveness in experimental models of bronchial hypersensitivity and hyperreactivity

  • C. Loesberg
  • F. M. A. Woutersen-van Nijnanten
  • F. P. Nijkamp
Histamine and Kinins


Respiratory histaminergic and cholinergic receptor function was investigated in isolated tracheal spirals of guinea pigs receiving different diets. Comparison was made between saline treated (controls) and Haemophilus influenzae treated animals in non sensitized conditions, the latter being a model for bronchial hyperreactivity, and in sensitized conditions, being a model for allergen induced bronchial hypersensitivity.

The different semi-synthetic diets (35 energy% fat)*, varying in linoleic acid content (5.85, 11.25 and 22.05 en% fat) and one diet with low linoleic acid (3.55 en%) in which linolenic acid was added additionally (5.30 en%), exerted profound effects on tracheal reactivity to histamine. In sensitized animals the maximal induced histamine contraction was significantly diminished in the dietary group receiving 5.85 en% linoleic acid as compared with the other dietary groups (35% decrease in the H. influenzaetreated, 20–30% decrease in saline treated animals). Results in non-sensitized animals were similar, though less pronounced. No effect on food intake or growth of the animals could be demonstrated during the six week experimental periods.

The carbachol induced contraction of the tracheal spirals of sensitized animals receiving low linoleic acid was also significantly decreased as compared to the other dietary groups (30% for saline treated and 20–30% for H. influenzae-treated animals). No difference in carbachol responsiveness could be detected between the different dietary groups under non-sensitized conditions. The results are discussed in view of the current concepts for bronchial hyperreactivity, especially in relation to eicosanoid involvement.


Histamine Linoleic Acid Eicosanoid Dietary Group Carbachol 
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  1. [1]
    E. W. Horton,Hypothesis on physiological roles of prostaglandins, Physiol. Rev.49, 122–161 (1969).PubMedGoogle Scholar
  2. [2]
    J. Orehek, J. S. Douglas, A. J. Lewis and A. Bouhuys,Prostaglandin regulation of airway smooth muscle tone, Nature245, 84–85 (1973).Google Scholar
  3. [3]
    M. Hitchcock,Stimulation of the antigen-induced contraction of guinea pig lung by (2-isopropyl-3-indoyl)-pyridyl keton (L8027) and indomethacin, Br. J. Pharmacol.71, 65–73 (1980).PubMedGoogle Scholar
  4. [4]
    C. Brink, P. G. Duncan, M. Midzenski and J. S. Douglas,Response and sensitivity of female guinea pig respiratory tissue to agonists during ontogenesis, J. Pharmacol. Exp. Ther.215, 426–433 (1980).PubMedGoogle Scholar
  5. [5]
    C. Brink, P. G. Duncan and J. S. Douglas,The response and sensibility to histamine of respiratory tissue from normal and ovalbuin sensitized guinea pigs: effects of cyclooxygenase and lipoxygenase inhibition. J. Pharmacol. Exp. Ther.217, 592–601 (1981).PubMedGoogle Scholar
  6. [6]
    J. F. Burka and N. A. M. Paterson,Evidence for lipoxygenase involvement in allergic tracheal contraction, Prostaglandins19, 499–515 (1980).PubMedGoogle Scholar
  7. [7]
    J. F. Burka and N. A. M. Paterson,Enhancement of antigen-induced tracheal contraction by cyclooxygenase inhibition, Adv. Prostagl. Thrombox. Res.8, 1755–1758 (1980).Google Scholar
  8. [8]
    P. Eyre and N. Chand,Histamine receptors in the lung. InPharmacology of histamine receptors, pp. 298–322 (Eds. C. R. Ganellin and E. Parsons), Wright PSG, Bristol 1972.Google Scholar
  9. [9]
    C. Loesberg, G. Folkerts, F. M. A. Woutersen-van Nijnanten and F. P. Nijkamp,Effects of dietary poly-unsaturated fatty acids on beta-adrenergic receptor reactivity in the guinea pig respiratory system, Agents Actions19, 359–360 (1986).CrossRefPubMedGoogle Scholar
  10. [10]
    S. Amir, M. Harel and A. Schachar,Thyrotropin-Releasing Hormone (TRH) improves survival in anaphylactic shock: A central effect mediated by the sympatho-adrenomedullary β-adrenoceptive system, Brain Res.298, 219–224 (1984).CrossRefPubMedGoogle Scholar
  11. [11]
    A. J. M. Schreurs and F. P. Nijkamp,Haemophilus influenzae induced loss of lung β-adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input, Eur. J. Pharmacol.77, 95–102 (1982).CrossRefPubMedGoogle Scholar
  12. [12]
    A. De Lean, P. J. Munson and R. Rodbard,Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay and pharmacological dose-response curves, Am. J. Physiol.235, E97-E102 (1978).PubMedGoogle Scholar
  13. [13]
    H. O. J. Collier and G. W. L. James,Humoral factors affecting pulmonary inflation during acute anaphylaxis in the guinea pig in vivo, Br. J. Pharmacol. Chemother.30, 283–301 (1967).Google Scholar
  14. [14]
    R. P. Orange, W. S. Austen and K. K. Austen,Immunologic release of histamine and slow reacting substance of anaphylaxis from human lung. I Modulation by agents influencing cellular levels of cyclic 3′5′ adenosine monophosphate, J. Exp. Med.134, Suppl. 136–148 (1971).Google Scholar
  15. [15]
    G. K. Adams and L. Lichtenstein,In vitro studies of antigen-induced bronchospasm: effect of anti-histamine and SRS-A antagonist on response of sensitized guinea pigs and human airways to antigen, J. Immunol.122, 555–562 (1979).PubMedGoogle Scholar
  16. [16]
    A. J. M. Schreurs, G. T. Terpstra, J. A. M. Raaijmakers and F. P. Nijkamp,The effects of Haemophilus influenzae vaccination on anaphylactic mediator release and isoprenaline-induced inhibition of mediator release, Eur. J. Pharmacol.62, 261–268 (1980).CrossRefPubMedGoogle Scholar
  17. [17]
    A. J. M. Schreurs, G. K. Terpstra, J. A. M. Raaijmakers and F. P. Nijkamp,Effects of vaccination with Haemophilus influenzae on adrenoceptor function of tracheal and parenchymal strips, J. Pharmacol. Exp. Ther.215, 691–696 (1980).PubMedGoogle Scholar
  18. [18]
    A. J. M. Schreurs and F. P. Nijkamp,Bronchial hyperreactivity histamine induced by Haemophilus influenzae vaccination, Agents Actions15, 211–215 (1984).CrossRefPubMedGoogle Scholar
  19. [19]
    W. R. Moyle, E. Y. Lee, O. P. Bahl, J. E. Garfink and D. Rodbard,New method for quantifying ligand binding based on measurement of an induced response, Am. J. Physiol.232, E274-E285 (1977).PubMedGoogle Scholar
  20. [20]
    J. M. May, P. W. Abel and K. P. Minneman,Binding of agonists and antagonists to β-adrenoceptors in rat vas deferns: relationship to functional response, Naunyn-Schmiedeberg's Arch. Pharmacol.331, 324–333 (1985).CrossRefGoogle Scholar
  21. [21]
    P. J. Piper and J. R. Vane,Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs, Nature223, 29–35 (1969).PubMedGoogle Scholar
  22. [22]
    J. F. Burka,Antigen-induced contraction of guinea pig trachea: search for mediator release with cascade superfusion bioassay, Br. J. Pharmacol.77, 3–5 (1982).PubMedGoogle Scholar
  23. [23]
    J. F. Burka and N. A. M. Paterson,The effects of SRS-A and histamine antagonists on antigen-induced contraction of guinea pig trachea, Eur. J. Pharmacol.70, 489–499 (1981).CrossRefPubMedGoogle Scholar
  24. [24]
    A. J. M. van Oosterhout and F. P. Nijkamp,Anterior hypothalamic lesions decrease anaphylactic contractions in guinea pig trachea in vitro by reducing histamine and LTC 4 reactivity, Int. J. Immunopharmacol.8, 975–983 (1986).CrossRefPubMedGoogle Scholar
  25. [25]
    A. Szentivanyi,The β-adrenergic theory of atopic abnormality in bronchial asthma, J. Allergy42, 203–232 (1968).Google Scholar
  26. [26]
    W. H. Anderson, J. J. Krzanowski, J. P. Polson and A. Szentivanyi,Increased synthesis of prostaglandin like material during histamine tachyphylaxis in canine tracheal smooth muscle, Biochem. Pharmacol.28, 2223–2226 (1979).CrossRefPubMedGoogle Scholar
  27. [27]
    W. H. Anderson, J. J. Krzanowski, J. P. Polson and A. Szentivanyi,Prostaglandins as mediators of tachyphylaxis to histamine in canine smooth muscle, Adv. Prostagl. Thrombox. Res.7, 995–1001 (1980).Google Scholar
  28. [28]
    J. J. Krzanowski, W. H. Anderson, J. B. Polson and A. Szentivanyi,Prostaglandin mediated histamine tachyphylaxis in subhuman primate tracheal smooth muscle, Arch. Int. Pharmacodyn.247, 155–162 (1980).PubMedGoogle Scholar
  29. [29]
    J. E. Fish, L. S. Jameson, A. Albright and P. S. Norman,Modulation of bronchomotor effects of chemical mediators by prostaglandin F in asthmatic subjects, Am. Rev. Resp. Dis.130, 571–574 (1984).PubMedGoogle Scholar
  30. [30]
    S. A. Shore, W. S. Powell and W. G. Martin,Endogenous prostaglandins modulate histamine-induced contraction of canine smooth muscle, J. Appl. Physiol.58, 859–868 (1985).PubMedGoogle Scholar
  31. [31]
    J. Orehek, J. S. Douglas and A. Bouhuys,Contractile responses of guinea pig trachea in vitro: modification by prostaglandin synthesis-inhibiting drugs, J. Pharmacol. Exp. Ther.194, 554–564 (1975).PubMedGoogle Scholar
  32. [32]
    R. J. Gryglewski and A. Ocetkiewics,A release of prostaglandins may be responsible for acute tolerance to norepinephrine infusion, Prostaglandins8, 31–42 (1974).CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1987

Authors and Affiliations

  • C. Loesberg
    • 1
  • F. M. A. Woutersen-van Nijnanten
    • 1
  • F. P. Nijkamp
    • 1
  1. 1.Institute of Veterinary Pharmacology, Pharmacy and Toxicology, Department of PharmacologyState University of UtrechtUtrechtThe Netherlands

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