title: Potential role of vasomotor effects of fibrinogen in bradykinin-induced angioedema.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hals-Nasen-Ohrenklinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Murat
authors.initials: M
authors.lastname: Bas
authors.forename: Nadine
authors.initials: N
authors.lastname: Kirchhartz
authors.forename: Jessica
authors.initials: J
authors.lastname: Hochfeld
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tüllmann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kumpf
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Suvorava
authors.forename: Marc
authors.initials: M
authors.lastname: Oppermann
authors.forename: Dieter
authors.initials: D
authors.lastname: Hafner
authors.forename: Henning
authors.initials: H
authors.lastname: Bier
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: Vera
authors.initials: V
authors.lastname: Balz
authors.forename: Georg
authors.initials: G
authors.lastname: Kojda
mesh_terms: D000368:Aged; D000799:Angioedema / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D001920:Bradykinin / Q000097:blood / Q000633:toxicity*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D005260:Female; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D012008:Recurrence; D013552:Swine; D013895:Thoracic Arteries / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000097:blood / Q000633:toxicity*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D005340:Fibrinogen; D001920:Bradykinin