Effects of bosentan and ambrisentan on antigen-induced arthritis (AIA). (a) Schematic drawing of experimental setup. Animals were immunized 21 and 14 days before induction of AIA. Mice received repeated oral applications of 100 mg/kg bosentan, 10 mg/kg ambrisentan, or saline (Control) every 24 hours beginning 2 hours before induction of AIA. Dexamethasone was given intraperitoneally (i.p.) at a dose of 0.6 mg/kg for 5 days beginning 12 hours before induction of AIA. Joint swelling and pain-related behavior were assessed as indicated. All animals were tested twice during the immunization procedure to obtain baseline values depicted as day 0. (b) Inhibition of knee joint swelling by bosentan but not by ambrisentan. Knee joint swelling as an indicator of inflammation was assessed by measuring the mediolateral diameter of each knee. (c) Inhibition of knee joint swelling by dexamethasone. (d) Lack of inhibition of thermal hyperalgesia by bosentan or ambrisentan. Thermal hyperalgesia was determined with an algesiometer and calculated as reduced withdrawal threshold to heat. (e) Inhibition of thermal hyperalgesia by dexamethasone. (f) Inhibition of mechanical hyperalgesia by bosentan but not by ambrisentan. Mechanical hyperalgesia was determined on ipsi- and contralateral hindpaws by using a dynamic plantar aesthesiometer. The weight force needed to elicit a response was read out in grams. (g) Inhibition of mechanical hyperalgesia by dexamethasone. Values in (b-e) are means ± standard error of the mean. The results from two-way analysis of variance followed by the Bonferroni post hoc test are shown (*P < 0.05; ο, not significant). p.o., per os (by mouth).