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

Coats, P., Johnston, F., MacDonald, J., McMurray, J. J.V. and Hillier, C. (2001) Endothelium-derived hyperpolarizing factor: identification and mechanisms of action in human subcutaneous resistance arteries. Circulation, 103(12), pp. 1702-1708. (doi: 10.1161/01.CIR.103.12.1702) (PMID:11274000)

Abstract

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-mediated vasorelaxation, however, was sensitive to the phospholipase A2 inhibitor oleyloxyethyl phosphorylcholine and the CYP450 inhibitor ketoconazole. Conclusions—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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Coats, P., Johnston, F., MacDonald, J., McMurray, J. J.V., and Hillier, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation
• Publisher: American Heart Association
• ISSN: 0009-7322
• ISSN (Online): 1524-4539