Endothelium-derived hyperpolarizing factor: Identification and mechanisms of action in human subcutaneous resistance arteries

Background—Both a vascular endothelial cytochrome P450 (CYP450) product of arachidonic acid metabolism and the potassium ion (K+) have been identified as endothelium-derived hyperpolarizing factors (EDHFs) in animal vascular tissues. We studied the relative importance of EDHF, nitric oxide (NO), and prostacyclin (PGI2) as vasodilators in human subcutaneous arteries. We also examined the mechanisms underlying the vasodilator action of EDHF to elucidate its identity. Methods and Results—Subcutaneous resistance arteries were obtained from 41 healthy volunteers. The contribution of EDHF to the vasodilation induced by acetylcholine was assessed by inhibiting production of NO, PGI2, and membrane hyperpolarization. The mechanisms underlying the relaxation evoked by K+ and EDHF were elucidated. EDHF was found to account for ≈80% of acetylcholine-mediated vasorelaxation. Its action was insensitive to the combination of barium and ouabain, whereas barium and ouabain reversed K+-mediated vasorelaxation. EDHF-mediate...