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The role of kinin B1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents
  1. Cássia R Silva1,
  2. Sara M Oliveira1,
  3. Carin Hoffmeister2,
  4. Vinícius Funck2,
  5. Gustavo P Guerra3,
  6. Gabriela Trevisan1,
  7. Raquel Tonello1,
  8. Mateus F Rossato1,
  9. João B Pesquero4,
  10. Michael Bader5,
  11. Mauro S Oliveira2,
  12. Jason J McDougall6,
  13. Juliano Ferreira1,2,7
    1. 1Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil
    2. 2Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil
    3. 3Center for Food Sciences, Federal Technologic University of Paraná, Medianeira, PR, Brazil
    4. 4Department of Biophysics, Universidade Federal de São Paulo, São Paulo, SP, Brazil
    5. 5Max-Delbrück-Center for Molecular Medicine (MDC) and Charité, University Medicine, Berlin, Germany
    6. 6Departments of Pharmacology and Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
    7. 7Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
    1. Correspondence to Dr Juliano Ferreira, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Centro de Ciências Biológicas, Bairro Trindade, Florianópolis, Santa Catarina 88040-900, Brasil; ferreiraj99{at}


    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-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 B1 agonist des-Arg9-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.

    • Arthritis
    • Gout
    • Inflammation

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