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

Byrd JB, Shreevatsa A, Putlur P, Foretia D, McAlexander L, Sinha T, Does MD, Brown NJ
J Allergy Clin Immunol. 2007 120 (2): 403-8

PMID: 17531305 · DOI:10.1016/j.jaci.2007.04.012

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.

MeSH Terms (14)

Angiotensin-Converting Enzyme Inhibitors Animals Animals, Genetically Modified Blood Pressure Captopril Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Dipeptidyl Peptidase 4 Disease Susceptibility Edema Magnetic Resonance Imaging Male Rats Rats, Inbred F344 Tracheal Diseases

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