Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema.
BACKGROUND: Serum dipeptidyl peptidase IV (DPPIV) activity is decreased in some individuals with ACE inhibitor-associated angioedema. ACE and DPPIV degrade substance P, an edema-forming peptide. The contribution of impaired degradation of substance P by DPPIV to the pathogenesis of ACE inhibitor-associated angioedema is unknown. OBJECTIVES: We sought to determine whether DPPIV deficiency results in increased edema formation during ACE inhibition. We also sought to develop an animal model using magnetic resonance imaging to quantify ACE inhibitor-induced edema. METHODS: The effect of genetic DPPIV deficiency on peritracheal edema was assessed in F344 rats after treatment with saline, captopril (2.5 mg/kg), or captopril plus the neurokinin receptor antagonist spantide (100 mug/kg) by using serial T2-weighted magnetic resonance imaging. RESULTS: Serum dipeptidyl peptidase activity was dramatically decreased in DPPIV-deficient rats (P < .001). The volume of peritracheal edema was significantly greater in captopril-treated DPPIV-deficient rats than in saline-treated DPPIV-deficient rats (P = .001), saline-treated rats of the normal substrain (P < .001), or captopril-treated rats of the normal substrain (P = .001). Cotreatment with spantide attenuated peritracheal edema in captopril-treated DPPIV-deficient rats (P = .005 vs captopril-treated DPPIV-deficient rats and P = .57 vs saline-treated DPPIV-deficient rats). CONCLUSIONS: DPPIV deficiency predisposes to peritracheal edema formation when ACE is inhibited through a neurokinin receptor-dependent mechanism. Magnetic resonance imaging is useful for modeling ACE inhibitor-associated angioedema in rats. CLINICAL IMPLICATIONS: Genetic or environmental factors that decrease DPPIV activity might increase the risk of ACE inhibitor-associated angioedema.[1]References
- Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. Byrd, J.B., Shreevatsa, A., Putlur, P., Foretia, D., McAlexander, L., Sinha, T., Does, M.D., Brown, N.J. J. Allergy Clin. Immunol. (2007) [Pubmed]
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