학술논문
The role of kinin B1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents
Document Type
Academic Journal
Author
Silva, Cássia R; Oliveira, Sara M; Hoffmeister, Carin; Funck, Vinícius; Guerra, Gustavo P; Trevisan, Gabriela; Tonello, Raquel; Rossato, Mateus F; Pesquero, João B; Bader, Michael; Oliveira, Mauro S; McDougall, Jason J; Ferreira, Juliano; Cabrini, Daniela; Fernanda Werner, Maria; Fleith Otuki, Michel; Reid, Allison; Krustev, Eugene
Source
Annals of the Rheumatic Diseases. Jan 01, 2016 75(1):260-268
Subject
Language
English
ISSN
0003-4967
Abstract
OBJECTIVE: Verify the role of the kinin B1 receptors (B1R) and the effect of ACE inhibitors (ACEi) on acute gout induced by monosodium urate (MSU) crystals in rodents. METHODS: Painful (overt pain and allodynia) and inflammatory parameters (joint oedema, leukocyte trafficking, interleukin-1β levels) of acute gout attacks were assessed several hours after an intra-articular injection of MSU (1.25 or 0.5 mg/articulation) into the ankle of rats or mice, respectively. The role of B1R was investigated using pharmacological antagonism or gene deletion. Additionally, B1R immunoreactivity in ankle tissue and sensory neurons, kininase I activity and des-Arg-bradykinin synovial levels were also measured. Similar tools were used to investigate the effects of ACEi on a low dose of MSU (0.0125 mg/articulation)-induced inflammation. RESULTS: Kinin B1R antagonism or gene deletion largely reduced all painful and inflammatory signs of gout. Furthermore, MSU increased B1R expression in articular tissues, the content of the B1 agonist des-Arg-bradykinin and the activity of the B1 agonist-forming enzyme kininase I. A low dose of MSU crystals, which did not induce inflammation in control animals, caused signs of acute gout attacks in ACEi-treated animals that were B1R-dependent. CONCLUSIONS: Kinin B1R contributes to acute gouty attacks, including the ones facilitated by ACEi. Therefore, B1R is a potential therapeutic target for the treatment and prophylaxis of gout, especially in patients taking ACEi.