Inhibition of rats adjuvant arthritis by a bradykinin antagonist hoe 140 and its influence on kallikreins

Abstract

1. 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. 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. 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. 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.