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

Hamilton, K., Dunning, L., Ferrell, W. R., Lockhart, J. C. and MacKenzie, A. (2018) Endothelium-derived contraction in a model of rheumatoid arthritis is mediated via angiotensin II type 1 receptors. Vascular Pharmacology, 100, pp. 51-57. (doi: 10.1016/j.vph.2017.11.001) (PMID:29122658)

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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.

Item Type:Articles
Additional Information:This work was supported by the Institute for Biomedical and Environmental Health Research, University of the West of Scotland.
Keywords:Angiotensin II type 1 receptor, endothelium-derived constricting factor, inflammation, losartan, rheumatoid arthritis.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ferrell, Professor William and Lockhart, Professor John
Authors: Hamilton, K., Dunning, L., Ferrell, W. R., Lockhart, J. C., and MacKenzie, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Vascular Pharmacology
Publisher:Elsevier
ISSN:1537-1891
ISSN (Online):1879-3649
Published Online:07 November 2017
Copyright Holders:Copyright © 2017 Crown Copyright
First Published:First published in Vascular Pharmacology 100: 51-57
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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