title: Angiotensin II Type 1 receptor blockade protects endothelium-derived hyperpolarising factor-mediated relaxation in a rat model of monoarthritis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Centre for Musculoskeletal Science, Institute of Biomedical and Environmental Health Research, School of Science, University of the West of Scotland, Paisley, UK. andrew.mackenzie@uws.ac.uk
authors: Andrew
authors: A
authors: Mackenzie
authors: Lynette
authors: L
authors: Dunning
authors: William R
authors: WR
authors: Ferrell
authors: John C
authors: JC
authors: Lockhart
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001241:Aspirin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology*; D005260:Female; D019808:Losartan / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D009213:Myography; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D045462:Endothelium-Dependent Relaxing Factors; D044140:Receptor, Angiotensin, Type 1; D018999:Charybdotoxin; D019808:Losartan; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester