Losartan protects endothelium-dependent relaxation in vivo in a murine model of rheumatoid arthritis

Moanna Villaluz, Lynette Dunning, Carl S. Goodyear, William R. Ferrell, John C. Lockhart, Andrew MacKenzie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Angiotensin II-type 1 receptor stimulation is recognised to promote inflammation, a state central to the development and maintenance of rheumatoid arthritis. Herein we examined the use of losartan, an angiotensin II-type 1 receptor antagonist, on vascular reactivity, knee joint diameter and behavioural assessment of pain in a Freund’s complete adjuvant (FCA) mouse model of joint inflammation.

Monoarthritis was induced via FCA in the presence or absence of losartan with naive mice serving as controls. Knee joint swelling, joint pain (assessed by dynamic weight bearing of limb use), knee joint artery reactivity (assessed ex vivo) and blood perfusion of the knee joint (assessed in vivo) were determined.

FCA mediated a significant increase in knee joint diameter and reduced weight-bearing (a surrogate for pain sensation) of the affected limb. Notably, these phenomena were substantially reduced when mice were prophylactically treated with losartan. Assessment of arterial relaxation and blood perfusion with acetylcholine stimulation revealed that FCA resulted in significant vascular dysfunction, which was resolved to naïve levels with losartan treatment.

Through the actions of losartan, these findings indicate that the angiotensin II-type 1 receptor is a likely therapeutic target of importance in the development of the physical changes, pain sensation and vascular dysfunction found in inflammatory arthritis.
Original languageEnglish
Article number174133
Number of pages7
JournalEuropean Journal of Pharmacology
Volume904
Early online date10 May 2021
DOIs
Publication statusPublished - 5 Aug 2021

Keywords

  • rheumatoid arthritis
  • losartan
  • angiotensin II-type 1 receptor
  • endothelium

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