HHcy-impaired EDHF-mediated vascular relaxation via inhibition of SKs and IKs in SMAs. SMAs were isolated from Tg-hCBS Cbs mice. (A) K_Ca blocker–inhibited EDHF-mediated relaxation. SMAs were pretreated with the COX inhibitor INDO (10μM), the NOS inhibitor L-NAME (100μM), and the K_Ca blocker TEA (1mM), precontracted with PE, and examined for relaxation to the cumulative additions of ACH. (B) SK blocker–inhibited EDHF-mediated relaxation. SMAs were pretreated with INDO, L-NAME, and the SK blocker apamin (1μM), precontracted with PE, and examined for relaxation to ACH. (C) IK blocker–inhibited EDHF-mediated relaxation. SMAs were pretreated with INDO, L-NAME, and the IK blocker Tram34 (1μM), precontracted with PE, and examined for relaxation to ACH. (D) SK/IK blocker–inhibited EDHF-mediated relaxation. SMAs were pretreated with INDO, L-NAME, apamin, and Tram34, precontracted with PE, and examined for relaxation to ACH. (E) K_ca-controlled maximal relaxation of K_ca. Maximal relaxation was calculated by subtracting the blocker inhibited EDHF-mediated relaxation (−5.5 log M; Figure 2A-C) from that of EDHF-mediated relaxation in the absence of blocker (Figure 1I). Value in the CT group treated with K_Ca blocker was defined as 100%. Values are means ± SEM (n = 5-7 mice, 2 vessel segments/mouse). *P < .05 compared with control mice. CT indicates the control group.