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

Abstract

AbstractTo investigate the role of mitochondrial KATP (mitoKATP) channels in potassium channel opener (KCO)‐induced relaxation and its relationship with the endothelium‐derived hyperpolarizing factor (EDHF)‐mediated relaxation, isometric force was measured in porcine coronary microarteries (100–400 µm) mounted in a four‐channel myograph. In the rings precontracted with U46619 (−8 logM), in the presence of glibenclamide (GBC, 3 µM) or 5‐hydroxydecanoate (5‐HD, 100 µM), concentration–relaxation curves for KRN4884 or diazoxide were established. The EDHF‐mediated relaxation was induced by bradykinin (BK) in the presence of indomethacin (Indo), NG‐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 (KCa) blocker charybdotoxin and apamin. Thus, both KRN4884 and diazoxide cause endothelium‐independent vasorelaxation through opening sarcoKATP channels. While KCa channels play a role in mediating the EDHF‐mediated relaxation, neither sarcoKATP nor mitoKATP channels are likely involved in this vasculature. Drug Dev. Res. 58:90–95, 2003. © 2003 Wiley‐Liss, Inc.