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

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Item Type:	Article
Title:	The role of kinin B1 receptor and the effect of angiotensin I-converting enzyme inhibition on acute gout attacks in rodents
Creators Name:	Silva, C.R., Oliveira, S.M., Hoffmeister, C., Funck, V., Guerra, G.P., Trevisan, G., Tonello, R., Rossato, M.F., Pesquero, J.B., Bader, M., Oliveira, M.S., McDougall, J.J. and Ferreira, J.
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-1beta 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.
Keywords:	Arthritis, Gout, Inflammation, Animals, Mice, Rats
Source:	Annals of the Rheumatic Diseases
ISSN:	0003-4967
Publisher:	BMJ Publishing Group
Volume:	75
Number:	1
Page Range:	260-268
Date:	January 2016
Official Publication:	https://doi.org/10.1136/annrheumdis-2014-205739
PubMed:	View item in PubMed

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