Bradykinin and the pathophysiology of angioedema

https://doi.org/10.1016/S1567-5769(02)00162-5Get rights and content

Abstract

Angioedema has different causes and different clinical presentations. Some types of angioedema may be mediated by bradykinin.

We measured plasma levels of bradykinin-(1–9)nonapeptide by radioimmunoassay after high-performance liquid chromatography in patients with different types of angioedema during acute attacks and/or in remission, i.e. hereditary C1-inhibitor deficiency, angiotensin converting enzyme (ACE) inhibitor treatment, idiopathic non histaminergic and responders to antihistamines.

Eleven patients with the deficiency of C1-inhibitor had very high levels of bradykinin during acute attacks of angioedema (18.0–90.0 pM) (normal range 0.2–7.1 pM). In three patients with history of ACE inhibitor-related angioedema, plasma bradykinin was high during ACE inhibitor treatment (62.0, 8.9 and 27.0 pM) and in a fourth patient was 47.0 pM during an acute attack and decreased by 93% to 3.2 pM after withdrawal of the ACE inhibitor. The patient with idiopathic angioedema, during an acute attack involving the right arm, had high levels of bradykinin in the venous blood refluent from the angioedematous arm (20.0 pM) while in the contralateral arm bradykinin levels were normal (6.6 pM), similarly to what we previously observed in cases of brachial angioedema due to C1-inhibitor deficiency. The four patients with angioedema responsive to antihistamines had normal levels of bradykinin even during acute attacks (5.7, 3.4, 4.7 and 1.2 pM). In one of these patients who had a brachial angioedema, bradykinin levels were normal in the venous blood refluent from both arms.

Bradykinin is involved in hereditary C1-inhibitor deficiency angioedema, in ACE inhibitor-related angioedema, and in idiopathic non-histaminergic angioedema, while bradykinin is not related to allergen-dependent or idiopathic angioedema that are responsive to antihistamines.

Section snippets

Clinical presentation of angioedema

Angioedema is a swelling involving the deeper layers of the skin or submucosal tissue and tends to recur chronically. It is most often located on the lips and face (Fig. 1), hands or feet. If angioedema occurs in the upper airways, particularly at the larynx, it is life-threatening. It may also occur in the gastrointestinal tract, where it can be very painful and can be mistaken for appendicitis, diverticulitis or mesenterial ischemia. It may cause diarrhea or ileus-like symptoms. Angioedema

Etiology of angioedema

Angioedema is caused by various reasons such as allergies, inherited or acquired deficiencies of C1-inhibitor or drug reactions. In many cases of angioedema, the pathophysiology remains undetermined. The clinical response to specific antagonists can provide a good evidence for a particular mediator. Histamine, which can be blocked by anti-histamines, is the best identified mediator [1], [2]. The reaction to an allergen induces the release of histamine and other chemicals. However, at the site

Pathogenesis of angioedema and the kinin system

Theoretically, at least two forms of angioedema may be due to bradykinin-mediated increase in vasopermeability: (1) angioedema due to C1-inhibitor deficiency and (2) ACE inhibitor-related angioedema.

Measurement of plasma bradykinin

We measured plasma levels of bradykinin-(1–9)nonapeptide by radioimmunoassay after liquid phase extraction and high-performance liquid chromatography [26]. Our method enabled us to solve several pre-analytical and analytical problems which have rendered extremely difficult the measurement of plasma kinins in the past [27]. The preanalytical problems consist in the very low concentration of bradykinin (pM), its short half life (seconds) and its easy enzymatic generation and degradation during

Bradykinin in different types of angioedema

During remission between angioedema attacks, plasma bradykinin in 26 patients with angioedema due to C1-inhibitor deficiency (22 hereditary and 4 acquired) was normal or slightly increased (3.9±3.7 and 10.4±1.6 pM, respectively; normal range 0.2–7.1 pM) [26]. During acute attacks of angioedema, in 11 patients plasma bradykinin was increased from 2 to 12 times the upper limit of normal (18.0–90.0 pM) [26], [28]. In two other patients with C1-inhibitor deficiency, we had the opportunity to

References (30)

  • J. Nussberger et al.

    Local bradykinin generation in hereditary angioedema

    J. Allergy Clin. Immunol.

    (1999)
  • A. Agostoni et al.

    Angioedema due to angiotensin-converting enzyme inhibitors

    Immunopharmacology

    (1999)
  • M.D. Thrap

    Chronic urticaria. Pathophysiology and treatment approaches

    J. Allergy Clin. Immunol.

    (1996)
  • A. Agostoni et al.

    Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients

    Medicine (Baltimore)

    (1992)
  • M. Cicardi et al.

    Hereditary angioedema

    N. Engl. J. Med.

    (1996)
  • Cited by (0)

    This paper is part of the Proceedings of the 16th International Conference on the Kallikrein-Kinin System (Kinin 2002) which was held in Charleston, SC, May 26–31, 2002 (see International Immunopharmacology Volume 2/13–14)

    View full text