1. This study examines the effect of Hoe 140, a bradykinin (BK) 2 receptor antagonist, indomethacin and prednisolone on chronic adjuvant arthritis of the knee in rats. We also evaluated the influence of Hoe 140 on BK-forming enzymes in the synovial and paw tissues. 2. Adjuvant arthritis was induced in male Sprague-Dawley rats in the right knee by injecting 0.05 ml of a fine suspension of heat-killed Mycobacterium tubercle bacilli in liquid paraffin (5 mg/ml). 3. Hoe 140 (1.5 mg/kg i.p.), indomethacin (2.5 mg/kg orally) and prednisolone (3.0 mg/kg orally) administration for 9 days resulted in significant suppression of knee joint swelling. Plasma and tissue kallikrein levels were raised (P < 0.01) in the synovial and paw tissues of adjuvant arthritic rats. Hoe 140 treatment reduced (P < 0.05) tissue kallikrein but increased (P < 0.01) plasma kallikrein levels in synovial tissue. 4. Hoe 140 treatment did not alter (P > 0.05) the raised plasma and tissue kallikrein levels in the paw tissue. The findings indicate that Hoe 140 may be a useful anti-inflammatory agent and BK plays a major role in this adjuvant-induced arthritis model.
The present study aimed to evaluate the effect of Hoe 140, a BK receptor B(2) antagonist, on acute oedema induced by carrageenan, BK and kaolin in male Wistar Kyoto rats. Hoe 140 (0.2 mg/kg and 20 mg/kg) given ip caused significant (p<0.05 and p<0.01) inhibition of carrageenan and BK-induced paw oedema. This suggests that BK is the prime inflammatory mediator of carrageenan oedema, and that it is also a specific blocker of oedema caused by BK. Furthermore, Hoe 140 was found to be less effective in reducing kaolin-induced oedema in rats. This might reflect that BK is not a prime inflammatory mediator of kaolin-induced oedema. The possible significance of these findings is discussed.