Published Online
on November 19, 2007

A more recent version of this article appeared on January 1, 2008

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Submitted on June 21, 2007
Revised on July 7, 2007

Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema

James Brian Byrd; Karine Touzin; Saba Sile; James V. Gainer; Chang Yu; John Nadeau; Albert Adam; and Nancy J. Brown^*

From the Departments of Medicine (J.B.B., S.S., J.V.G., J.N., N.J.B.), and Biostatistics (C.Y.), Vanderbilt University Medical School, Nashville, Tenn; Faculty of Pharmacy (K.T., A.A.), University of Montreal, Montreal, Quebec, Canada; and Veterans Administration Medical Center (J.V.G., J.N.), Nashville, Tenn.

^* To whom correspondence should be addressed. E-mail: nancy.j.brown{at}vanderbilt.edu.

Abstract—Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor–associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor–associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor–associated angioedema and 176 angiotensin-converting enzyme inhibitor–exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg⁹-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6±7.8 versus 29.6±7.3 nmol/mL per minute; P=0.026) and antigen (465.8±260.8 versus 563.1±208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor–associated angioedema compared with angiotensin-converting enzyme inhibitor–exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5±4.9 versus 29.8±6.7 nmol/mL per minute; P=0.001) and antigen (354.4±124.7 versus 559.8±163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.

Key words: angiotensin-converting enzyme inhibitors • angioneurotic edema • antigens • CD26 • substance P • neuropeptides • bradykinin

Related Article:

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Eric Grouzmann and Thierry Buclin
Hypertension 2008 51: 45-47. [Extract] [Full Text] [PDF]

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