Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema

James Brian Byrd, Ajai Shreevatsa, Pradeep Putlur, Denis Foretia, Laurie McAlexander, Tuhin Sinha, Mark D. Does, Nancy J. Brown

Research output: Contribution to journalArticlepeer-review

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)403-408
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number2
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

Keywords

  • Angioedema
  • angiotensin-converting enzyme inhibitor
  • dipeptidyl peptidase IV
  • larynx
  • magnetic resonance imaging
  • neurokinin
  • pharmacogenetics
  • spantide
  • substance P
  • trachea

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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