Effect of enalapril on allergen-induced cutaneous hypersensitivity reaction.
1. To test the hypothesis that the in vivo inhibition of angiotensin converting enzyme in a patient who presents atopy, results in a significant increase in cutaneous bradykinin and prostaglandin production, the effect of enalapril on the cutaneous hypersensitivity reaction was examined in 10 atopic volunteers. 2. A crossover study design was used and volunteers were randomly allocated to treatment with either enalapril (10 mg) alone, or in combination with indomethacin (75 mg), with and without ketotifen (1 mg). Drugs were administered twice daily for 2 days. 3. Allergen (Southern Grass Mix) was administered intradermally 2 h after last drug dosage and the surface areas of the immediate wheal-and-flare-reactions were measured 15 min later. The late phase of the cutaneous response was evaluated 6 h later by determining skinfold thickness and surface area. 4. Enalapril alone had no effect on any of the parameters measured. 5. The cutaneous hypersensitivity reaction was significantly reduced with regard to both immediate and late cutaneous responses when the indomethacin and ketotifen combination was added to enalapril therapy. 6. When only indomethacin was added to enalapril pretreatment the flare reaction was significantly reduced, but whealing was unaffected. 7. This study presents further evidence that mast cell mediators other than prostaglandins are involved in the cutaneous hypersensitivity reaction. Furthermore, that endogenous bradykinin production after enalapril pretreatment either never reaches the supraphysiological concentrations used in previous experiments, or that bradykinin is rapidly and effectively broken down to inactive peptides by other carboxypeptidase enzymes.
Snyman
J R
JR
Department of Pharmacology, University of Pretoria, South Africa.
Sommers
D K
DK
D000284:Administration, Oral; D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D007213:Indomethacin / Q000009:adverse effects; D007665:Ketotifen / Q000627:therapeutic use; D008297:Male; D011897:Random Allocation; D012867:Skin / Q000187:drug effects*
D000485:Allergens; D004656:Enalapril; D007665:Ketotifen; D007213:Indomethacin