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

Show simple item record Silva, Cassia R. Oliveira, Sara M. Hoffmeister, Carin Funck, Vincius Guerra, Gustavo P. Trevisan, Gabriela Tonello, Raquel Rossato, Mateus F. Pesquero, Joao B. [UNIFESP] Bader, Michael Oliveira, Mauro S. McDougall, Jason J. Ferreira, Juliano 2019-01-21T10:30:19Z 2019-01-21T10:30:19Z 2016
dc.identifier.citation Annals Of The Rheumatic Diseases. London, v. 75, n. 1, p. 260-268, 2016.
dc.identifier.issn 0003-4967
dc.description.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. en
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Canadian Institutes of Health Research
dc.format.extent 260-268
dc.language.iso eng
dc.publisher Bmj Publishing Group
dc.relation.ispartof Annals Of The Rheumatic Diseases
dc.rights Acesso restrito
dc.subject Joint Urate Arthritis en
dc.subject Synovial-Fluid en
dc.subject B1 Receptors en
dc.subject Human-Plasma en
dc.subject Rat Paw en
dc.subject Bradykinin en
dc.subject Activation en
dc.subject Il-1-Beta en
dc.subject Model en
dc.subject Mice en
dc.title The role of kinin B-1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents en
dc.type Artigo
dc.description.affiliation Univ Fed Santa Maria, Grad Program Biol Sci Toxicol Biochem, BR-97119900 Santa Maria, RS, Brazil
dc.description.affiliation Univ Fed Santa Maria, Grad Program Pharmacol, BR-97119900 Santa Maria, RS, Brazil
dc.description.affiliation Fed Technol Univ Parana, Ctr Food Sci, Medianeira, PR, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Biophys, Sao Paulo, SP, Brazil
dc.description.affiliation Max Delbruck Ctr Mol Med MDC, Berlin, Germany
dc.description.affiliation Charite, D-13353 Berlin, Germany
dc.description.affiliation Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada
dc.description.affiliation Dalhousie Univ, Dept Anesthesia, Pain Management & Perioperat Med, Halifax, NS, Canada
dc.description.affiliation Univ Fed Santa Catarina, Dept Farmacol, BR-88040900 Florianopolis, SC, Brazil
dc.description.affiliationUnifesp Univ Fed Santa Catarina, Dept Farmacol, Ctr Ciencias Biol, Campus Univ Reitor Joao David Ferreira Lima, BR-88040900 Florianopolis, SC, Brazil.
dc.identifier.doi 10.1136/annrheumdis-2014-205739
dc.description.source Web of Science
dc.identifier.wos WOS:000366402400035


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