Comparison of the effects of the ace inhibitors trandolapril and enalapril on phlogogen induced foot pad oedema in the rat
- 20 Downloads
Two angiotensin converting enzyme (ACE) inhibitors, trandolapril and enalapril, were compared for their effects on rat food-pad oedema induced by carrageenin, bradykinin dextran and platelet activating factor (PAF). Trandolapril (0.03–30.0 mg/kg, per os) potentiated carrageenin-induced oedemas. Enalapril produced the same effect at 3–10 fold higher doses (0.3–30.0 mg/kg per os). Both ACE inhibitors were equiactive in potentiating bradykinin-induced oedema. Neither compound affected dextran-induced oedema. In marked contrast PAF-induced oedema was reduced by both ACE inhibitors, trandolapril being approximately 10 fold more active than enalapril. The observed differences in potency between the two ACE inhibitors corresponded with their previously described actions on inhibition of plasma and tissue ACE and in inducing hypotension. The results suggest a crucial role of kinins in the oedemagenic response to carrageenin. The reason why the ACE inhibitors reduced PAF-induced oedema is not clear, but could involve peripheral vasodilation.
Unable to display preview. Download preview PDF.
- G. P. Lewis,Kinins in inflammation and tissue injury. In:“Bradykinin, Kallidin and Kallikrein”. Handb. Exp. Pharmac, pp. 516–530 (Ed. E. G. Erdos). Springer-Verlag Berlin, Heidelberg (1970).Google Scholar
- F. Marceau, A. Lussier, D. Reboli and J. P. Giroud,Pharmacology of kinins: their relevance to tissue injury and inflammation, Gen. Pharmac.14, 209–229 (1983).Google Scholar
- J. Damas and G. Remacle-Volon,Role des kinines dans l'oedème tégumentaire déclenché par les carragénines chez le rat, J. Pharmacol. (Paris)13, 225–239 (1981).Google Scholar
- A. L. A. Boura and A. P. Svolmanis,Converting enzyme inhibition in the rat by captopril is accompanied by potentiation of carrageenin-induced inflammation, Br. J. Pharmac.82, 3–8 (1984).Google Scholar
- G. Caspritz, H. G. Alpermann and R. Schleyerbach,Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat, Arzneim.-Forsch./Drug Res.36, 1605–1608 (1986).Google Scholar
- Y. Matsuno, H. Hori, M. Oka, H. Nakamura, T. Ito and T. Kadokowa,General pharmacology of the novel angiotensin converting enzyme inhibitor alacepril: effects on control nervous and sensory systems and on the other functions, Arzneim. Forsch./Drug Res.36, 62–68 (1986).Google Scholar
- N. L. Brown, J. Fichelle, J. C. Vincent and M. Worcel,Cardiovascular profile of trandolapril a new angiotensin convertin enzyme (ACE) inhibitor, Br. J. Pharmac.90, 203P (1987).Google Scholar
- N. L. Brown, C. Chevillard and M. Worcel,Difference between trandolapril and enalapril for inhibition of tissue ACE activity in rats, Br. J. Pharmac.90, 204P (1987).Google Scholar
- C. V. Wedmore and T. J. Williams,Platelet-activing factor (PAF), a secretory product of polymorphonuclear leucocytes, increases vascular permeability of rabbit skin, Br. J. Pharmacol.74, 916P-917P (1981).Google Scholar
- C. S. Sweet, D. M. Gross, P. T. Arbegast, S. L. Gaul, P. M. Britt, C. L. Ludden, D. Weitz and C. A. Stone,Antihypertensive activity of N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-l-Ala-l-Pro (MK 421), an orally active converting enzyme inhibitor, J. Pharmacol. Exp. Ther.216, 558–566 (1981).PubMedGoogle Scholar