TY - JOUR AU - Han, Eun D. AU - MacFarlane, Ryan C. AU - Mulligan, Aideen N. AU - Scafidi, Jennifer AU - Davis, Alvin E., III T1 - Increased vascular permeability in C1 inhibitor–deficient mice mediated by the bradykinin type 2 receptor PY - 2002/04/15/ AB - Heterozygosity for C1 inhibitor (C1INH) deficiency results in hereditary angioedema. Disruption of the C1INH gene by gene trapping enabled the generation of homozygous- and heterozygous-deficient mice. Mating of heterozygous-deficient mice resulted in the expected 1:2:1 ratio of wild-type, heterozygous, and homozygous-deficient offspring. C1INH-deficient mice showed no obvious phenotypic abnormality. However, following injection with Evans blue dye, both homozygous and heterozygous C1INH-deficient mice revealed increased vascular permeability in comparison with wild-type littermates. This increased vascular permeability was reversed by treatment with intravenous human C1INH, with a Kunitz domain plasma kallikrein inhibitor (DX88), and with a bradykinin type 2 receptor (Bk2R) antagonist (Hoe140). In addition, treatment of the C1INH-deficient mice with an angiotensin-converting enzyme inhibitor (captopril) increased the vascular permeability. Mice with deficiency of both C1INH and Bk2R demonstrated diminished vascular permeability in comparison with C1INH-deficient, Bk2R-sufficient mice. These data support the hypothesis that angioedema is mediated by bradykinin via Bk2R. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI14211 VL - 109 IS - 8 UR - https://doi.org/10.1172/JCI14211 SP - 1057 EP - 1063 PB - The American Society for Clinical Investigation ER -