Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema.

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-Arg(9)-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.

• Authors: James Brian Byrd, Karine Touzin, Saba Sile, James V Gainer, Chang Yu, John Nadeau, Albert Adam, Nancy J Brown
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 51 Issue 1 Pg. 141-7 (Jan 2008) ISSN: 1524-4563 [Electronic] United States
• PMID: 18025295 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antigens
• Substance P
• Dipeptidyl Peptidase 4
• Peptidyl-Dipeptidase A
• Bradykinin

Topics

• Adult
• Aged
• Angioedema (chemically induced, enzymology)
• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Antigens (immunology)
• Bradykinin (metabolism)
• Case-Control Studies
• Dipeptidyl Peptidase 4 (genetics, immunology, metabolism)
• Female
• Genetic Predisposition to Disease
• Humans
• Hypertension (drug therapy)
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (metabolism)
• Substance P (metabolism)