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

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2 Citations (Scopus)
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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
Number of pages7
JournalVascular Pharmacology
Early online date7 Nov 2017
DOIs
Publication statusE-pub ahead of print - 7 Nov 2017

Keywords

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

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