Drugs

, Volume 41, Supplement 1, pp 48–53

Enalaprilat, but not Cilazaprilat, Increases Inflammatory Skin Reactions in Guinea-Pigs

  • Rolf G. G. Andersson
  • Bengt E. Karlberg
  • Björn R. Lindgren
  • Karin Persson
  • Ulf Rosenqvist
Article

Summary

The inflammatory effects of enalaprilat and cilazaprilat were tested in an experimental model of ovalbumin-sensitised guinea-pigs.

Enalaprilat, but not cilazaprilat, enhanced the ovalbumin-induced inflammatory skin responses. The effect of enalaprilat was dose-dependent. Enalaprilat significantly increased the skin content of substance P and histamine. Cilazaprilat did not alter the level of these inflammatory mediators.

Enalaprilat, applied locally, but not cilazaprilat, enhanced the inflammatory reactions caused by intradermal injections of allergen and substance P. Both angiotensin converting enzyme (ACE) inhibitors enhanced the inflammatory skin response evoked by bradykinin.

Our study strongly indicates that enalaprilat has pro-inflammatory properties, whereas the new long-acting ACE inhibitor cilazaprilat does not. This might give a better safety profile of cilazaprilat.

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References

  1. Andersson RGG, Karlberg BE, Lindgren BR. Cough and other bronchial symptoms and skin disorders during treatment with ACE inhibitors. Läkartidningen 84: 183–184, 1987Google Scholar
  2. Boulet LP, Cartier A, Thompson NC, Robert RS, Dolovich J, et al. Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure. Journal of Allergy and Clinical Immunology 71: 399–406, 1983PubMedCrossRefGoogle Scholar
  3. Casciere MA, Bull HG, Mumford RA, Patchett AA, Thornberry NA, et al. Carboxy-terminal tripetidyl hydrolysis of substance P by purified rabbit lung angiotensin converting enzyme and the potentiation of substance P activity in vivo by captopril and MK 422. Molecular Pharmacology 25: 287–293, 1983Google Scholar
  4. Chalmers D, Dombey SL, Lawson DH. Marketing surveillance of captopril (for hypertension): a preliminary report. British Journal of Clinical Pharmacology 24: 343–349, 1987PubMedCrossRefGoogle Scholar
  5. Couture R, Regoli D. Inactivation of substance P and its C-terminal fragments in rat plasma and its inhibition by captopril. Canadian Journal of Physiology and Pharmacology 59: 621–624, 1981PubMedCrossRefGoogle Scholar
  6. Edwards IR, Coulter DM, Beasley DMG, McIntosh D. Captopril: four years of post-marketing surveillance of all patients in New Zealand. British Journal of Clinical Pharmacology 23: 529–536, 1987PubMedCrossRefGoogle Scholar
  7. Ferguson RK, Brunner HR, Turini GA, Gavras H, McKinstry DN. A specific orally active inhibitor of angiotensin-converting enzyme in man. Lancet 1: 775–778, 1977PubMedCrossRefGoogle Scholar
  8. Ferguson RK, Vlasses PH, Rothmensch HH. Clinical applications of the angiotensin converting enzyme inhibitors. American Journal of Medicine 77: 690–698, 1984PubMedCrossRefGoogle Scholar
  9. Ferreira SH. A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. British Journal of Pharmacology and Chemotherapy 24: 163–169, 1965PubMedGoogle Scholar
  10. Fügner A. Pharmacological aspects of immediate hypersensitivity reactions in vivo. In Devlin JP (Ed.) Pulmonary and antiallergic drugs, pp. 123–190, Wiley, New York, 1985Google Scholar
  11. Fuller RW, Warren JB, McCusker, Dollery CT. Effect of enalapril on the skin response to bradykinin in man. British Journal of Clinical Pharmacology 23: 88–90, 1987PubMedCrossRefGoogle Scholar
  12. Fyhrquist F. Clinical pharmacology of the ACE inhibitors. Drugs 32 (Suppl. 5): 33–39, 1986PubMedCrossRefGoogle Scholar
  13. Joint National Committee. The 1988 report of the joint national committee on detection, evaluation and treatment of high blood pressure. Archives of Internal Medicine 148: 1023–1038, 1988CrossRefGoogle Scholar
  14. Lindgren BR, Andersson CD, Andersson RGG. Potentiation of inflammatory reactions in guinea-pig skin by an angiotensin converting enzyme inhibitor (MK 422). European Journal of Pharmacology 135: 383–387, 1987PubMedCrossRefGoogle Scholar
  15. Lindgren BR, Persson K, Kihlström JE, Andersson RGG. ACE-inhibitor induced enhancement of spontaneous and IgE-mediated histamine release from mast cells and basophilic leucocytes and the modulatory effect of capsaicin sensitive nerves. Pharmacology and Toxicology 64: 159–164, 1989aPubMedCrossRefGoogle Scholar
  16. Lindgren BR, Rosenqvist U, Ekström T, Grönneberg R, Karlberg BE, et al. Increased bronchial reactivity and potentiated anti-IgE-induced skin responses in hypertensive subjects suffering from coughs during angiotensin converting enzyme inhibitor therapy. Chest 95: 1225–1230, 1989bPubMedCrossRefGoogle Scholar
  17. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the phenol reagent. Journal of Biological Chemistry 193: 265–275, 1951PubMedGoogle Scholar
  18. Ondetti MA, Rubin B, Chusman DW, Cheung HS, Sabo FF. Design of specific inhibitors of angiotensin converting enzyme: new class of orally active antihypertensive agents. Science 196: 441–444, 1977PubMedCrossRefGoogle Scholar
  19. Skidgel RA, Engelbrecht S, Johnson AR, Erdös EG. Hydrolysis of substance P and neurotensin by converting enzyme and neutral endopeptidase. Peptides 5: 769–776, 1984PubMedCrossRefGoogle Scholar
  20. Suarez M, Ho PW, Johnson ES, Perez G. Angioneurotic edema, agranulocytosis, and fatal septicemia following captopril therapy. American Journal of Medicine 336–338, 1986Google Scholar
  21. Town GI, Hallwright GP, Maling T, O’Donnel TV. Angiotensin converting enzyme inhibitors and cough. New Zealand Medical Journal 100: 161–163, 1987PubMedGoogle Scholar
  22. Wilkin JK, Hammon JJ, Kirkendall WM. The captopril-induced eruption. Archives of Dermatological Research 116: 902–905, 1980Google Scholar
  23. World Health Organization International Society of Hypertension (WHO/ISH). Guidelines for the management of mild hypertension. Memorandum from WHO/ISH Meeting, 5th Mild Hypertension Conference 1989. Journal of Hypertension 7: 689–693, 1989CrossRefGoogle Scholar
  24. Wood SM, Mann RD. Angio-oedema and urticaria associated with angiotensin converting enzyme inhibitors. British Medical Journal 294: 91–92, 1987PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Rolf G. G. Andersson
    • 1
  • Bengt E. Karlberg
    • 1
  • Björn R. Lindgren
    • 1
  • Karin Persson
    • 1
  • Ulf Rosenqvist
    • 1
  1. 1.Departments of Pharmacology and Medicine, Faculty of Health SciencesLinköping UniversityLinköpingSweden

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