Angiotensin II Type 1 receptor blockade protects endothelium-derived hyperpolarising factor-mediated relaxation in a rat model of monoarthritis

MacKenzie, A., Dunning, L., Ferrell, W. R. and Lockhart, J. C. (2013) Angiotensin II Type 1 receptor blockade protects endothelium-derived hyperpolarising factor-mediated relaxation in a rat model of monoarthritis. Life Sciences, 92(23), pp. 1131-1137. (doi: 10.1016/j.lfs.2013.04.011) (PMID:23643673)

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Abstract

Aims: Rheumatoid arthritis (RA) is associated with high cardiovascular mortality. Impaired endothelial cell (EC) function and elevated angiotensin II levels may be central to the link between vascular dysfunction and RA. Here we investigated the action of angiotensin type 1 receptor (AT1R) blockade on endothelium-dependent relaxation of the isolated saphenous artery in a rat model of monoarthritis.<p></p> Main Methods: Adjuvant arthritis was induced in rats with and without prophylactic losartan (AT1R antagonist) treatment. Vehicle-treated rats were used as controls. Wire myography was employed to investigate EC function of isolated rings of saphenous artery.<p></p> Key Findings: EC-dependent relaxation in arteries from non-inflamed control rats was mediated by both nitric oxide (NO) and endothelium-derived hyperpolarising factor (EDHF) with the EDHF response dependent principally on functional myoendothelial gap junctions. While NO-dependent relaxation remained unaffected, the EDHF-mediated response was abolished in arteries from arthritic rats (P < 0.001), however, substantial protection (approximately 50%) of the EDHF-relaxation was found in arthritic rats treated with losartan (P < 0.01). Thus, the attenuated EDHF response found in the saphenous artery of arthritic rats was significantly reversed by AT1R blockade.<p></p> Significance: These results suggest a key role for the angiotensin system in the EC dysfunction found in chronic joint inflammation and highlights AT1R as a potential therapeutic target to redress the vascular impairment and mortality associated with RA.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ferrell, Professor William and Dunning, Mrs Lynette and Lockhart, Professor John
Authors: MacKenzie, A., Dunning, L., Ferrell, W. R., and Lockhart, J. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Life Sciences
Publisher:Elsevier Inc.
ISSN:0024-3205
ISSN (Online):1879-0631

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