Skip to main content
Log in

Exaggerated hypotension byN-formylmethionylleucylphenylalanine in indomethacin pretreated rats. Role of toxic oxygen

  • Immunosuppression and Inflammation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

In pentobarbital anaesthetized rats the intravenous administration of the oligopeptideN-formyl-Met-Leu-Phe (FMLP) is shown to produce a short-lasting hypotension. When the animals have been pretreated with indomethacin, FMLP induces a marked and sustained blood pressure fall. This exaggerated hypotensive response to FMLP is absent in rats which have received a low dose of endotoxin at the day before, and is greatly reduced in animals treated with ascorbic acid or dimethylsulfoxide. In addition, the duration of hypotension is shortened in rats which have been partially depleted of leukocytes by daily methotrexate dosages, or which simultaneously receive drug treatments known to enhance vessel wall cyclic AMP levels like isoprenaline, glucagon or theophylline. The results suggest that after the FMLP administration toxic oxygen species generated by leukocytes contribute to the development of the cardiovascular dysfunction. Endothelial cAMP is suggested to control the sensitivity of the cardiovascular system to these reactive species.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. H.J. Showell, R.J. Freer, S.H. Zigmond, E. Schiffmann, S. Aswanikumar, B. Corcoran andE.L. Becker,The structure activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils, J. exp. Med.143, 1154–1169 (1976).

    PubMed  Google Scholar 

  2. J. Palmblad, H. Gyllenhammar, J. Å. Lindgren andC.L. Malmsten,Effects of leukotrienes and f-Met-Leu-Phe on oxidative metabolism of neutrophils and eosinophils, J. Immunol.132, 3041–3045 (1984).

    PubMed  Google Scholar 

  3. R.M. Palmer andJ.A. Salmon,Release of leukotriene B 4 from human neutrophils and its relationship to degranulation induced by N-formyl-methionyl-leucylphenylalanine, serum treated zymosan and the ionophore A 23187, Immunology50, 65–77 (1983).

    PubMed  Google Scholar 

  4. R.B. Gilbertsen, G.W. Carter andD.J. Quinn,Effects of F-Met-Leu-Phe and zymosan-activated serum on rat neutrophils in vivo, J. Reticuloendoth. Soc.,27, 485–494 (1980).

    Google Scholar 

  5. R. Hamel, A.W. Ford-Hutchinson, A. Lord andM. Cirino,Bronchoconstriction induced by N-formylmethionyl-leucyl-phenylalanine in the guinea pig; involvement of arachidonic acid metabolites. Prostaglandins28, 43–56 (1984).

    PubMed  Google Scholar 

  6. J.C. Fantone, R.E. Duque andS.H. Phan,Prostaglandin modulation of N-formyl-methionylleucylphenylalanine-induced transmembrane potential changes in rat neutrophils, Biochim. Biophys. Acta804, 265–274 (1984).

    PubMed  Google Scholar 

  7. E.A. Ham, D.D. Soderman, M.E. Zanetti, H.W. Dougherty, E. McCauley andF.A. Kuehl,Inhibition by prostaglandins of leukotriene B 4 release from activated neutrophils, Proc. Natl. Acad. Sci.80, 4349–4353 (1983).

    PubMed  Google Scholar 

  8. M.J. Parnham, C. Bittner andJ. Winkelmann,Macrophages from different sources, their production of chemiluminescence under various stimuli and the effects of PGE 2 and drugs, Agents and Actions11, 617–619 (1981).

    PubMed  Google Scholar 

  9. A. Marone, A. Kagey-Sobotka andL.M. Lichtenstein,Effect of arachidonic acid and its metabolites on antigen-induced histamine release from human basophils in vitro, J. Immunol.123, 1669–1677 (1979).

    PubMed  Google Scholar 

  10. K.U. Malik andJ.C. McGiff,Modulation by prostaglandin E 1 of adrenergic transmission in isolated perfused rabbit and rat kidney, Circ. Res.36, 599–609 (1975).

    PubMed  Google Scholar 

  11. D.F. Horrobin, M.S. Manku, R.A. Karmali, B.A. Nassar andP.A. Davies,Aspirin, indomethacin, catecholamine and prostaglandin interactions on rat arterioles and rabbit hearts, Nature250, 425–426 (1974).

    PubMed  Google Scholar 

  12. A.I. Cederbaum andG. Cohen, Microsomal oxidant radical production and ethanol oxidation. InMethods in enzymology, oxygen radicals in biological systems, vol. 105, pp. 516–522 (Ed.L. Parker). Academic Press, 1984.

  13. L. Frank, J. Summerville andD. Massaro,Protection from oxygen toxicity with endotoxin; role of the endogenous antioxidant enzymes of the lung, J. Clin. Invest.65, 1104–1110 (1980).

    PubMed  Google Scholar 

  14. J.T. Berg andR.M. Smith,Endotoxin protection of rats from O 2 toxicity: chemiluminescence of lung neutrophils, Res. Commum. Chem. Path. Pharmacol.44, 461–476 (1984).

    Google Scholar 

  15. S.G. Jenkinson, R.J. Long andR.A. Lawrence,Endotoxin protects selenium-deficient rats from hyperoxia, J. Lab. Clin. Med.103, 143–151 (1984).

    PubMed  Google Scholar 

  16. S.J. Weiss, J. Young, A.F. LoBuglio, A. Slivka andN.F. Nimeh,Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells, J. Clin. Invest.68, 714–721 (1981).

    PubMed  Google Scholar 

  17. F.S. Lamb andR.C. Webb,Vascular effects of free radicals generated by electrical stimulation, Am. J. Physiol.247, H709-H714 (1984).

    PubMed  Google Scholar 

  18. M.A. Trush, M.E. Wilson andK.V. Dyke, The generation of chemiluminescence by phagocytic cells. InMethods in enzymology, bioluminescence and chemiluminescence, vol. 57, pp. 462–494 (Ed.M.A. DeLuca). Academic Press, 1978.

  19. E.C. LeRoy, A. Ager andJ.L. Gordon,Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I 2 production, adenine nucleotide release, and responses to vasoactive agents, J. Clin. Invest.74, 1003–1010 (1984).

    PubMed  Google Scholar 

  20. N.K. Hopkins andR.R. Gorman,Regulation of endothelial cell cyclic nucleotide metabolism by prostacyclin, J. Clin. Invest.67, 540–546 (1981).

    PubMed  Google Scholar 

  21. A. F. A. Brotherton andJ. C. Hook,Role of Ca ++ and cyclic AMP in the regulation of the production of prostacyclin by the vascular endothelium, Proc. Natl. Acad. Sci.79, 495–499 (1982).

    PubMed  Google Scholar 

  22. K. Brune, M. Glatt, H. Kalin andB.A. Peskar,Pharmacological control of prostaglandin and thromboxane release from macrophages, Nature274, 261–263 (1978).

    PubMed  Google Scholar 

  23. A.C. Issekutz,Vascular responses during acute neutrophilic inflammation. Their relationship to in vivoneutrophil emigration, Lab. Invest.45, 435–441 (1981).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olsen, U.B., Bille-Hansen, V. Exaggerated hypotension byN-formylmethionylleucylphenylalanine in indomethacin pretreated rats. Role of toxic oxygen. Agents and Actions 17, 489–494 (1986). https://doi.org/10.1007/BF01965519

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01965519

Keywords

Navigation