In vivoexperiments
Experimental arthritis was induced under anaesthesia (halothane/O2/N2O) by intra-articular and peri-articular injection of Freund's complete adjuvant in adult male Wistar rats (350 ± 20 g body weight, mean ± SEM, n = 6). Knee joint swelling was measured using callipers and expressed as the percentage change from pre-induction values. The anti-inflammatory potential of losartan (Merck & Co., USA) was tested both prophylactically and therapeutically. Prophylactically, losartan (15 mg/kg; subcutaneous) was given 1 hour prior to induction of inflammation and every 48 hours thereafter. Therapeutically, 12 days after the induction of inflammation, losartan (15 mg/kg; subcutaneous) treatment was started and dosing continued every 48 hours. The mechanism of action of losartan was investigated using EXP 3174 (Merck & Co.), given prophylactically (15 mg/kg; subcutaneous, maintenance every 48 hours) 1 hour prior to induction of inflammation (Freund's complete adjuvant).