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

Autor 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
Resumo 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.
Assunto Joint Urate Arthritis
Synovial-Fluid
B1 Receptors
Human-Plasma
Rat Paw
Bradykinin
Activation
Il-1-Beta
Model
Mice
Idioma Inglês
Financiador Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Canadian Institutes of Health Research
Data 2016
Publicado em Annals Of The Rheumatic Diseases. London, v. 75, n. 1, p. 260-268, 2016.
ISSN 0003-4967 (Sherpa/Romeo, fator de impacto)
Editor Bmj Publishing Group
Extensão 260-268
Fonte http://dx.doi.org/10.1136/annrheumdis-2014-205739
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000366402400035
URI http://repositorio.unifesp.br/handle/11600/46090

Mostrar registro completo




Arquivos deste item

Arquivos Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item aparece na(s) seguinte(s) coleção(s)