In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints.
OBJECTIVE
Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor-mediated responses was also tested.


METHODS
Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees.


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 CB2 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.


CONCLUSIONS
In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated.
McDougall
J J
JJ
Department of Physiology & Biophysics, University of Calgary, Calgary, Alberta, Canada. mcdougaj@ucalgary.ca
Yu
V
V
Thomson
J
J
D000287:Administration, Topical; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007596:Joints / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D050916:TRPV Cation Channels / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology
D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014665:Vasodilator Agents