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.

1. The present study was performed to investigate some of the physiological responses to furosemide during postnatal maturation. 2. In 1- (n = 8) and 6-week old (n = 10) conscious, chronically instrumented lambs at least 3 days after surgery, three experiments were performed at intervals of 24-48 h and in random order. Various parameters of cardiovascular and endocrine function, as well as cumulative urinary flow rates, were measured before and after intravenous injection of 0 mg/kg (experiment one), 0.25 mg/kg (experiment two; low dose) and 5 mg/kg (experiment three; high dose) furosemide. 3. After high-dose furosemide, mean venous pressure decreased and there was a transient increase in mean arterial pressure in lambs aged 6 weeks. At 1 week of age, heart rate increased after high-dose furosemide and renal blood flow decreased. After high-dose furosemide, plasma renin activity increased in both groups of lambs, although the effects were greater in 1-week-old lambs. Plasma levels of arginine vasopressin increased after high-dose furosemide in lambs aged 1 but not 6 weeks. Cumulative urinary flow rate responses to furosemide were similar in 1- and 6-week-old lambs. 4. These data provide new information that cardiovascular and endocrine responses to furosemide are developmentally regulated.

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