The role of kinin B-1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents

The role of kinin B-1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents

Author Silva, Cassia R. Google Scholar
Oliveira, Sara M. Google Scholar
Hoffmeister, Carin Google Scholar
Funck, Vincius Google Scholar
Guerra, Gustavo P. Google Scholar
Trevisan, Gabriela Google Scholar
Tonello, Raquel Google Scholar
Rossato, Mateus F. Google Scholar
Pesquero, Joao B. Autor UNIFESP Google Scholar
Bader, Michael Google Scholar
Oliveira, Mauro S. Google Scholar
McDougall, Jason J. Google Scholar
Ferreira, Juliano Google Scholar
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-1 beta 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-Arg9-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 B-1 agonist des-Arg9-bradykinin and the activity of the B-1 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.
Keywords Joint Urate Arthritis
B1 Receptors
Rat Paw
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Canadian Institutes of Health Research
Date 2016
Published in Annals Of The Rheumatic Diseases. London, v. 75, n. 1, p. 260-268, 2016.
ISSN 0003-4967 (Sherpa/Romeo, impact factor)
Publisher Bmj Publishing Group
Extent 260-268
Access rights Closed access
Type Article
Web of Science ID WOS:000366402400035

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