Figure 2. The effect of the sEH inhibitor tAUCB on the K_Ca2.3 component of endothelium-dependent hyperpolarization (EDH) in rat middle cerebral arteries able to synthesize NO.

(A) Original traces of K_Ca2.3-mediated hyperpolarization obtained in the presence of: the K_Ca3.1 inhibitor TRAM-34 and K_Ca1.1 inhibitor iberiotoxin (upper trace), the subsequent addition of tAUCB (middle trace) and the combination of tAUCB and the K_Ca2.3 inhibitor, apamin. (B) Bar graph showing control EDH, K_Ca2.3 dependent EDH in the presence and absence of tAUCB and further addition of apamin. The K_Ca2.3-dependent hyperpolarization was significantly smaller than control EDH and was potentiated by tAUCB this hyperpolarization was completely abolished by apamin indicating that it was mediated solely by K_Ca2.3. (C) Bar graph showing the SLIGRL-induced EDH mediated hyperpolarization (left panel) and relaxation (right panel) in the presence of the NOS inhibitor L-NAME. TRAM-34 significantly attenuated EDH responses and the subsequent addition of t-AUCB had no further effect. Under these conditions, there is no contribution from K_Ca2.3 channels and tAUCB failed to restore the function of this channel. (D) Bar graphs showing the SLIGRL-induced EDH mediated hyperpolarization (left panel) and relaxation (right panel) in the presence tempol and the NOS inhibitor L-NAME. Tempol restored a K_Ca2.3 component to the EDH response and also revealed a K_Ca1.1 component (n = 5). ^∗P < 0.05 indicates a significant difference from control, ΨP < 0.05 indicates a significant difference from TRAM-34 + IbTx (K_Ca2.3 hyperpolarization).