Endothelium-derived contraction in a model of rheumatoid arthritis is mediated via angiotensin II type 1 receptors

Kayleigh Hamilton, Lynette Dunning, William R. Ferrell, John C. Lockhart, Andrew MacKenzie

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
147 Downloads (Pure)

Abstract

A role for endothelium-derived constricting factors (EDCF), and the angiotensin II type 1 receptor (AT1R) pathway, in the vascular impairment found in the rat Freund's complete adjuvant (FCA)-model of rheumatoid arthritis (RA) was examined. FCA arthritis was induced in rats ± losartan. Vehicle-treated rats served as controls. Knee-joint swelling and red blood cell (RBC) aggregation were measured as indicators of inflammation and endothelium reactivity assessed by response to acetylcholine (ACh) on aortic rings. Results show that knee-joint swelling and RBC aggregation were elevated in the FCA + vehicle group and restored to control levels in the FCA + losartan-treated animals. ACh-induced relaxation of aortic rings taken from FCA + vehicle animals was significantly impaired compared to vehicle-controls and this vasoreactivity was restored to control levels in the FCA + losartan-treated group. Further examination of aorta from the FCA + vehicle animals revealed an EDCF that was reliant on cyclooxygenase-2 (but not cyclooxygenase-1), generation of superoxide anion generation (but not hydrogen peroxide) and activation of thromboxane-prostanoid receptor. Losartan administration in vivo or ex vivo (to aortic rings) prevented the generation of the EDCF. In summary, this is the first evidence of an EDCF in a model of RA and identifies this mechanism as potentially significant in the cardiovascular disorder associated with the disease.
Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalVascular Pharmacology
Volume100
Early online date7 Nov 2017
DOIs
Publication statusPublished - 31 Jan 2018

Keywords

  • Endothelium-derived constricting factor
  • Angiotensin II type 1 receptor
  • Rheumatoid arthritis
  • Losartan
  • Inflammation

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