In vivo effects of CB 2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints

Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB 2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB 2 receptor‐mediated responses was also tested. Experimental approach: Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB 2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees. Key results: In normal animals, JWH015 and JWH133 caused a concentration‐dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB 2 receptor antagonist AM630 as well as the transient receptor potential vanilloid‐1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow. Conclusion and implications: In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB 2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated. British Journal of Pharmacology (2008) 153 , 358–366; doi: 10.1038/sj.bjp.0707565 ; published online 5 November 2007