ACE‐Inhibitor‐Induced Enhancement of Spontaneous and IgE‐Mediated Histamine Release from Mast Cells and Basophilic Leukocytes and the Modulatory Effect of Capsaicin Sensitive Nerves

Publisher Website
Google Scholar
Abstract
Frequently reported adverse inflammatory skin and airway reactions have been reported in subjects being medicated with angiotensin converting enzyme (ACE)‐inhibitors. Intradermally evoked wheal and flare reactions to ovalbumin, capsaicin and bradykinin, in ovalbumin sensitized guinea pigs, was previously demonstrated to be enhanced by pretreatment with the ACE‐inhibitor MK 422 (the active parent diacid of enalapril).In vitroresults from this study demonstrate that the ACE‐inhibitor MK 422 degranulated guinea pig lung and skin mast cells as well as human basophils, and enhanced allergen‐evoked histamine release. Local capsaicin pretreatmentin vivoof guinea pig skin decreased spontaneous and allergen‐triggered release of histaminein vitrofrom skin mast cells. No clear enhancing effect of MK 422 was seen on the allergen‐triggered histamine releasein vitrofrom capsaicin pretreated skin, and the spontaneous release was unaffected by the ACE‐inhibitor. The allergen‐triggered wheal and flare reaction in ovalbumin sensitized guinea pigs was potentiated by MK 422 and the late phase reaction of the inflammatory response was especially augmented. Capsaicin pretreatment of the guinea pigs abolished this late phase reaction as well as the inflammatory enhancing effect of MK 422. Ourin vitroresults from capsaicin pretreated skin indicate that the reduced inflammatory responsein vivoin capsaicin pretreated skin is due not only to capsaicin induced depletion of neuropeptides from sensory nerves, but also to secondary degranulation of mast cells by one or more of these peptides.