Figure 1.

Pretreatment with RvE1 concentration‐dependently inhibits U46619‐induced constriction of RTA segments. (A) Pretreatment with RvE1 at a concentration of 10 nM for 1 h significantly inhibited constriction of RTA segments induced by cumulative concentrations of U46619 (n = 8). (B) U46619‐induced constriction of RTA segments was also inhibited by RvE1 (10 nM) pretreatment for 24 h (n = 5). (C) Inhibition of U46619‐induced constriction was dependent on the concentration of RvE1 (0.1–300 nM) used during pretreatment for 1 h or (D) 24 h. In both instances, the greatest shift in U46619 EC₅₀ occurred at 10 nM RvE1. (E) The compound, CCX832, is a novel antagonist of the chemerin receptor, a receptor for RvE1. At 100 nM, CCX832 alone had no effect on U46619‐induced constriction of RTA segments. When added 15 min before a 1 h pretreatment with RvE1 (10 nM, n = 4), CCX832 reduced the inhibition by RvE1 of U46619‐induced constriction at both 10 and 30 nM of U46619, suggesting that the inhibitory action of RvE1 is mediated by chemerin receptors. (F) RvE1 (10 nM) pretreatment for 1 h did not affect constriction of RTA segments induced by the α₁‐adrenoceptor agonist PE, indicating a selective inhibitory activity of RvE1 against the thromboxane mimetic U46619.