BACKGROUND: Bradykinin is believed to be the main mediator of symptoms in hereditary (HA) and acquired (AA) angio-oedema due to C1 esterase inhibitor deficiency, as well as in angio-oedema that complicates treatment with inhibitors of angiotensin-converting enzyme (ACE). Difficulties in the measurement of kinin concentrations, however, have so far precluded the demonstration of an incontrovertible change in plasma bradykinin concentrations in these disorders. By developing a reliable assay we have been able to follow bradykinin concentrations during attacks and during remission in HA and in AA, and also in a patient treated with an ACE-inhibitor. METHODS: Liquid-phase extraction, high-performance liquid chromatography, and RIA were used for specific measurement of plasma bradykinin concentrations in 22 patients with HA and in 22 healthy volunteers of similar age and sex distribution. Four patients with AA and one hypertensive patient treated with the ACE inhibitor captopril were also studied. FINDINGS: Among the healthy volunteers plasma bradykinin concentration was inversely proportional to age. The geometric mean plasma bradykinin concentration in the healthy volunteers was 2.2 fmol/mL (SD 2.2), compared with 3.9 fmol/mL (3.7) among patients with HA during remission (p=0.095). Bradykinin was also high in the patients with AA (10.4 fmol/mL [1.6]). During acute attacks of oedema, in both HA and AA, plasma bradykinin rose to two to 12 times the upper limit of normal. Infusion of C1-esterase inhibitor (the deficient factor in both HA and AA) immediately lowered bradykinin concentrations. In the patient receiving the ACE-inhibitor captopril, bradykinin concentration was very high at 47 fmol/mL during an acute attack of angio-oedema, but normal at 3.2 fmol/mL in remission after withdrawal of the drug. INTERPRETATION: A sensitive method for measurement of plasma bradykinin provided the means to show that concentrations of this peptide decrease with age in healthy people. Although the differences between patients in remission and healthy controls did not reach statistical significance, there were substantial rises in bradykinin during acute attacks of hereditary, acquired, or captopril-induced angio-oedema.
BACKGROUND:Bradykinin is believed to be the main mediator of symptoms in hereditary (HA) and acquired (AA) angio-oedema due to C1 esterase inhibitor deficiency, as well as in angio-oedema that complicates treatment with inhibitors of angiotensin-converting enzyme (ACE). Difficulties in the measurement of kinin concentrations, however, have so far precluded the demonstration of an incontrovertible change in plasma bradykinin concentrations in these disorders. By developing a reliable assay we have been able to follow bradykinin concentrations during attacks and during remission in HA and in AA, and also in a patient treated with an ACE-inhibitor. METHODS: Liquid-phase extraction, high-performance liquid chromatography, and RIA were used for specific measurement of plasma bradykinin concentrations in 22 patients with HA and in 22 healthy volunteers of similar age and sex distribution. Four patients with AA and one hypertensivepatient treated with the ACE inhibitor captopril were also studied. FINDINGS: Among the healthy volunteers plasma bradykinin concentration was inversely proportional to age. The geometric mean plasma bradykinin concentration in the healthy volunteers was 2.2 fmol/mL (SD 2.2), compared with 3.9 fmol/mL (3.7) among patients with HA during remission (p=0.095). Bradykinin was also high in the patients with AA (10.4 fmol/mL [1.6]). During acute attacks of oedema, in both HA and AA, plasma bradykinin rose to two to 12 times the upper limit of normal. Infusion of C1-esterase inhibitor (the deficient factor in both HA and AA) immediately lowered bradykinin concentrations. In the patient receiving the ACE-inhibitor captopril, bradykinin concentration was very high at 47 fmol/mL during an acute attack of angio-oedema, but normal at 3.2 fmol/mL in remission after withdrawal of the drug. INTERPRETATION: A sensitive method for measurement of plasma bradykinin provided the means to show that concentrations of this peptide decrease with age in healthy people. Although the differences between patients in remission and healthy controls did not reach statistical significance, there were substantial rises in bradykinin during acute attacks of hereditary, acquired, or captopril-induced angio-oedema.
Authors: Angelo Agostoni; Emel Aygören-Pürsün; Karen E Binkley; Alvaro Blanch; Konrad Bork; Laurence Bouillet; Christoph Bucher; Anthony J Castaldo; Marco Cicardi; Alvin E Davis; Caterina De Carolis; Christian Drouet; Christiane Duponchel; Henriette Farkas; Kálmán Fáy; Béla Fekete; Bettina Fischer; Luigi Fontana; George Füst; Roberto Giacomelli; Albrecht Gröner; C Erik Hack; George Harmat; John Jakenfelds; Mathias Juers; Lajos Kalmár; Pál N Kaposi; István Karádi; Arianna Kitzinger; Tímea Kollár; Wolfhart Kreuz; Peter Lakatos; Hilary J Longhurst; Margarita Lopez-Trascasa; Inmaculada Martinez-Saguer; Nicole Monnier; István Nagy; Eva Németh; Erik Waage Nielsen; Jan H Nuijens; Caroline O'grady; Emanuela Pappalardo; Vincenzo Penna; Carlo Perricone; Roberto Perricone; Ursula Rauch; Olga Roche; Eva Rusicke; Peter J Späth; George Szendei; Edit Takács; Attila Tordai; Lennart Truedsson; Lilian Varga; Beáta Visy; Kayla Williams; Andrea Zanichelli; Lorenza Zingale Journal: J Allergy Clin Immunol Date: 2004-09 Impact factor: 10.793
Authors: Alexander P Haring; Emily G Thompson; Raymundo D Hernandez; Sahil Laheri; Megan E Harrigan; Taylor Lear; Harald Sontheimer; Blake N Johnson Journal: Adv Biosyst Date: 2019-12-05