title: The role of kinin B1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents.
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(9)-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(9)-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.
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Cássia R
authors.initials: CR
authors.lastname: Silva
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Oliveira
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Carin
authors.initials: C
authors.lastname: Hoffmeister
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Vinícius
authors.initials: V
authors.lastname: Funck
authors.affiliation: Center for Food Sciences, Federal Technologic University of Paraná, Medianeira, PR, Brazil.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Guerra
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Tonello
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Mateus F
authors.initials: MF
authors.lastname: Rossato
authors.affiliation: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: João B
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC) and Charité, University Medicine, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Oliveira
authors.affiliation: Departments of Pharmacology and Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists / Q000627:therapeutic use; D004149:Dioxoles / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000378:metabolism; D006073:Gout / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000139:chemically induced / Q000378:metabolism; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000502:physiology*; D013449:Sulfonamides / Q000627:therapeutic use; D014527:Uric Acid
chemical_list: C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D000806:Angiotensin-Converting Enzyme Inhibitors; D065169:Bradykinin B1 Receptor Antagonists; D004149:Dioxoles; D043783:Receptor, Bradykinin B1; D013449:Sulfonamides; D014527:Uric Acid
keywords: Arthritis; Gout; Inflammation