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- Title:
Potential role of vasomotor effects of fibrinogen in bradykinin-induced angioedema.
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- Bas, M; Kirchhartz, N; Hochfeld, J; Tüllmann, C; Kumpf, S; Suvorava, T; Oppermann, M; Hafner, D; Bier, H; Hoffmann, TK; Balz, V; Kojda, G
- Abstract:
- BACKGROUND: Although bradykinin is known to play a major role in the pathophysiology of hereditary and angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema, other factors acting as triggers or enhancers are likely important as well. OBJECTIVE: We hypothesized that fibrinogen might contribute to ACEi-induced angioedema (eg, through direct actions on vascular tone). METHODS: Plasma levels of fibrinogen were determined in 59 patients with acute angioedema. Vascular activity of human and bovine fibrinogen and its effects on bradykinin-induced vasodilation and phosphorylation of vasodilator-stimulated phosphoprotein were investigated in small (0.8-1.4 mm in diameter) porcine coronary artery and human internal thoracic artery (ITA) segments. RESULTS: In patients with ACEi-induced angioedema, fibrinogen levels (481 +/- 22 mg/dL, n = 39) were significantly higher than in patients with idiopathic angioedema (302 +/- 15 mg/dL, P < .001). Fibrinogen (1-15 mumol/L) induced a concentration-dependent vasodilation in preconstricted small porcine coronary arteries (n = 13), reaching a maximum vasodilator effect of 70% +/- 4.7%. Likewise, fibrinogen induced a 52.1% +/- 9.1% (n = 7) vasodilation in ITA rings. Fibrinogen vasorelaxations were completely inhibited by abciximab and diminished by endothelial denudation and treatment with the nitric oxide synthase inhibitor L-nitroargininemethylester and glibenclamide (P < .01). Importantly, fibrinogen increased the vasodilator potency of bradykinin by 10-fold (P < .0001) and increased bradykinin-induced vasodilator-stimulated phosphoprotein phosphorylation (P < .01). CONCLUSION: The increase of plasma fibrinogen levels, its vasodilator activity in human ITAs, and the potentiation of bradykinin-induced vasodilation suggest that fibrinogen might contribute to the pathophysiology of ACEi-induced angioedema. Thus acute-phase proteins, such as fibrinogen, might be viewed as risk factors for bradykinin-induced angioedema.
- Journal title abbreviation:
- J Allergy Clin Immunol
- Year:
- 2008
- Journal volume:
- 121
- Journal issue:
- 4
- Pages contribution:
- 969-75.e2
- Language:
- eng
- Fulltext / DOI:
- doi:10.1016/j.jaci.2008.01.071
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/18395553
- Print-ISSN:
- 0091-6749
- TUM Institution:
- Hals-Nasen-Ohrenklinik und Poliklinik
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