Role of sarcolemmal and mitochondrial KATP channels and EDHF-mediated relaxation in coronary microarteries

To investigate the role of mitochondrial K-ATP (mitoKATP) channels in potassium channel opener (KCO)-induced relaxation and its relationship with the endothelium-derived hyperpolarizing factor (FDHF)-mediated relaxation, isometric force was measured in porcine coronary microarteries (100-400 mum) mounted in a four-channel myograph. In the rings precontracted with U-46619 (-8 logM), in the presence of glibenclamide (GBC, 3 muM) or 5-hydroxydecanoate (5-HD, 100 PM), concentration-relaxation curves for KRN4884 or diazoxide were established. The EDHF-mediated relaxation was induced by bradykinin (BK) in the presence of inclomethacin (Indo), N-G-nitro-L-arginine (L-NNA), and oxyhemoglobin (HbO). Both KRN4884 and diazoxide caused concentration-dependent but endothelium-independent relaxations. GBC but not 5-HD inhibited these relaxations with increased EC50S (P<0.001)The EDHF-mediated relaxation was unaffected by either GBC or 5-HD but was reduced by the large and small conductance Ca2+-activated K+ channel (K-Ca) blocker charybdotoxin and apamin. Thus, both KRN4884 and diazoxide cause endothelium-independent vasorelaxation through opening sarcoK(ATP) channels. While K-Ca, channels play a role in mediating the EDHF-mediated relaxation, neither sarcoKATP nor mitoKATP channels are likely involved in this vasculature. (C) 2003 Wiley-Liss, Inc.