J V Gainer1, J H Nadeau, D Ryder, N J Brown. 1. Vanderbilt University Medical Center, Division of Clinical Pharmacology, Nashville, TN 37232-6602, USA.
Abstract
BACKGROUND: Angioedema is a potentially life-threatening side effect of angiotensin-converting enzyme (ACE) inhibitors. Although the mechanism of angioedema is not certain, bradykinin has been implicated in its pathogenesis. Compared with Caucasians, African Americans are at an increased risk of ACE inhibitor-associated angioedema, independent of ACE inhibitor dose or concurrent medications. Because urinary kallikrein levels are decreased in African Americans with hypertension, we hypothesized that endogenous bradykinin levels may be decreased in African Americans and that they therefore may be more sensitive to ACE inhibitor-induced increases in bradykinin or to exogenous bradykinin. OBJECTIVE: To test this hypothesis, we measured the wheal response to intradermal injection of bradykinin in salt-replete hypertensive and normotensive African Americans and Caucasians. METHODS: Two doses of bradykinin, 1 microgram and 10 micrograms, were administered on separate days in a randomized, double-blind fashion. RESULTS: Higher bradykinin dose (analysis of variance: F = 38.33, p < 0.001), African American race (analysis of variance: F = 17.90, p < 0.001), and hypertension (analysis of variance: F = 4.37, p = 0.05) were all associated with an increased wheal response to bradykinin. CONCLUSION: These data provide additional support for racial differences in the kallikrein-kinin system and also implicate abnormalities of the tissue kallikrein-kinin system in essential hypertension.
RCT Entities:
BACKGROUND:Angioedema is a potentially life-threatening side effect of angiotensin-converting enzyme (ACE) inhibitors. Although the mechanism of angioedema is not certain, bradykinin has been implicated in its pathogenesis. Compared with Caucasians, African Americans are at an increased risk of ACE inhibitor-associated angioedema, independent of ACE inhibitor dose or concurrent medications. Because urinary kallikrein levels are decreased in African Americans with hypertension, we hypothesized that endogenous bradykinin levels may be decreased in African Americans and that they therefore may be more sensitive to ACE inhibitor-induced increases in bradykinin or to exogenous bradykinin. OBJECTIVE: To test this hypothesis, we measured the wheal response to intradermal injection of bradykinin in salt-replete hypertensive and normotensive African Americans and Caucasians. METHODS: Two doses of bradykinin, 1 microgram and 10 micrograms, were administered on separate days in a randomized, double-blind fashion. RESULTS: Higher bradykinin dose (analysis of variance: F = 38.33, p < 0.001), African American race (analysis of variance: F = 17.90, p < 0.001), and hypertension (analysis of variance: F = 4.37, p = 0.05) were all associated with an increased wheal response to bradykinin. CONCLUSION: These data provide additional support for racial differences in the kallikrein-kinin system and also implicate abnormalities of the tissue kallikrein-kinin system in essential hypertension.
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: Alencia V Woodard-Grice; Amelia C Lucisano; James B Byrd; Elizabeth R Stone; William H Simmons; Nancy J Brown Journal: Pharmacogenet Genomics Date: 2010-09 Impact factor: 2.089
Authors: Murat Bas; Thomas K Hoffmann; Bernd Tiemann; Vu Thao-Vi Dao; Christos Bantis; Vera Balz; Hans-Jürgen Schultz-Coulon; Thomas Stark; Patrick Schuler; Jens Greve; Katrin Ivens; Henning Bier; Georg Kojda Journal: Br J Clin Pharmacol Date: 2010-02 Impact factor: 4.335
Authors: Cheng Gang; Christopher J Lindsell; Joseph Moellman; Wesley Sublett; Kim Hart; Sean Collins; Jonathan A Bernstein Journal: Allergy Asthma Proc Date: 2013 May-Jun Impact factor: 2.587
Authors: Rebecca J Kamil; Elina Jerschow; Patricia A Loftus; Melin Tan; Marvin P Fried; Richard V Smith; David Foster; Thomas J Ow Journal: Laryngoscope Date: 2016-01-04 Impact factor: 3.325