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Cyclooxygenase activity in bradykinin-induced dermal extravasation. A study in mice and humans.
Gholamreza-Fahimi, Ehsan; Bisha, Marion; Hahn, Janina; Straßen, Ulrich; Krybus, Michael; Khosravani, Farbod; Hoffmann, Thomas K; Hohlfeld, Thomas; Greve, Jens; Bas, Murat; Twarock, Sören; Kojda, Georg.
Affiliation
  • Gholamreza-Fahimi E; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany.
  • Bisha M; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany.
  • Hahn J; Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Ulm University Medical Center, Germany.
  • Straßen U; Otorhinolaryngology Department, University Hospital Rechts der Isar, Munich Technical University, Munich, Germany.
  • Krybus M; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany.
  • Khosravani F; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany; Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Ulm University Medical Center, Germany; Otorhinolaryngology Department, University Hospital Rechts der Isar, Munich Tec
  • Hoffmann TK; Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Ulm University Medical Center, Germany.
  • Hohlfeld T; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany.
  • Greve J; Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Ulm University Medical Center, Germany.
  • Bas M; Otorhinolaryngology Department, University Hospital Rechts der Isar, Munich Technical University, Munich, Germany.
  • Twarock S; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany.
  • Kojda G; Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany. Electronic address: kojda@uni-duesseldorf.de.
Biomed Pharmacother ; 123: 109797, 2020 Mar.
Article in En | MEDLINE | ID: mdl-31874445
BACKGROUND: Non-allergic angioedema is largely driven by increased plasma levels of bradykinin and over-activation of bradykinin receptor type II (B2), but the specific downstream signalling pathways remain unclear. The aim of this study was to identify signal transduction events involved in bradykinin-induced dermal extravasation. METHODS: Quantification of dermal extravasation was accomplished following intradermal (i.d.) injection of bradykinin or the B2 agonist labradimil in mice with endothelial NO-synthase (eNOS) deficiency and in C57BL/6J mice pre-treated with vehicle, NO-synthase or cyclooxygenase (COX) inhibitors. In the multicentre clinical study ABRASE, 38 healthy volunteers received i.d. bradykinin injections into the ventral forearm before and after oral treatment with the COX inhibitor ibuprofen (600 mg). The primary endpoint of ABRASE was the mean time to complete resolution of wheals (TTCR) and the secondary endpoint was the change of maximal wheal size. RESULTS: Neither NOS inhibitors nor eNOS deficiency altered bradykinin-induced extravasation. In striking contrast, the COX inhibitors ibuprofen, diclofenac, SC560 and celecoxib significantly diminished this extravasation when given before injection. As for diclofenac, a similar but significantly lower effect was observed when given after i.d. injection of bradykinin. Similar results were obtained when bradykinin was replaced by labradimil. In volunteers, ibuprofen significantly reduced TTCR (P < 0.001) and maximal wheal size (P = 0.0044). CONCLUSION: These data suggest that COX activity contributes to bradykinin-induced dermal extravasation in mice and humans. In addition, our findings may open new treatment options and point to a potential activity of drugs interfering with the release of the COX substrate arachidonic acid, e.g. glucocorticoids.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bradykinin / Prostaglandin-Endoperoxide Synthases / Dermis Type of study: Clinical_trials / Prognostic_studies Limits: Animals / Humans Language: En Journal: Biomed Pharmacother Year: 2020 Document type: Article Affiliation country: Alemania Country of publication: Francia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bradykinin / Prostaglandin-Endoperoxide Synthases / Dermis Type of study: Clinical_trials / Prognostic_studies Limits: Animals / Humans Language: En Journal: Biomed Pharmacother Year: 2020 Document type: Article Affiliation country: Alemania Country of publication: Francia