The role of kinin B1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents

Published on Jan 1, 2016in Annals of the Rheumatic Diseases16.102
· DOI :10.1136/ANNRHEUMDIS-2014-205739
Cássia Regina Silva21
Estimated H-index: 21
(UFSM: Universidade Federal de Santa Maria),
Sara Marchesan Oliveira25
Estimated H-index: 25
(UFSM: Universidade Federal de Santa Maria)
+ 10 AuthorsJuliano Ferreira53
Estimated H-index: 53
(UFSC: Universidade Federal de Santa Catarina)
Sources
Abstract
Objective Verify the role of the kinin B 1 receptors (B 1 R) 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 B 1 R was investigated using pharmacological antagonism or gene deletion. Additionally, B 1 R 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 B 1 R antagonism or gene deletion largely reduced all painful and inflammatory signs of gout. Furthermore, MSU increased B 1 R expression in articular tissues, the content of the B 1 agonist des-Arg 9 -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 B 1 R-dependent. Conclusions Kinin B 1 R contributes to acute gouty attacks, including the ones facilitated by ACEi. Therefore, B 1 R is a potential therapeutic target for the treatment and prophylaxis of gout, especially in patients taking ACEi.
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