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

P. Coats, F. Johnston, J. MacDonald, J.J.V. McMurray, C. Hillier

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)


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. 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 {approx}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-mediated vasorelaxation, however, was sensitive to the phospholipase A2 inhibitor oleyloxyethyl phosphorylcholine and the CYP450 inhibitor ketoconazole. EDHF is the major contributor to endothelium-dependent vasorelaxation in human subcutaneous resistance arteries. A product of phospholipase A2/CYP450-dependent metabolism of arachidonic acid and not K+ is the likely identity of EDHF in human subcutaneous resistance arteries.
Original languageEnglish
Pages (from-to)1702-8
Number of pages1694
Publication statusPublished - 2001


  • endothelium-derived factors
  • nitric oxide
  • physiology
  • biomedical science
  • circulatory system


Dive into the research topics of 'Endothelium-derived hyperpolarizing factor: identification and mechanisms of action in human subcutaneous resistance arteries'. Together they form a unique fingerprint.

Cite this