Endothelium-derived hyperpolarizing factor: a key mediator of the vasodilator action of bradykinin.

Bradykinin causes vasodilatation by stimulating the production of vasodilator prostanoids and nitric oxide (NO). However, there is an additional component that is mediated by a diffusible endothelium-derived hyperpolarizing factor (EDHF). The non-selective inhibitor of arachidonic acid metabolism eicosatetraynoic acid inhibits the EDHF-mediated component of the relaxation to bradykinin. Therefore, EDHF may be an archidonic acid metabolite. The diffusible nature of EDHF has been disputed because of the inability to consistently detect the factor using perfusion bioassay techniques. However, administration of the acyltransferase inhibitor thimerosal facilitates the release of EDHF by endothelial cells in culture. Further studies are warranted to identify EDHF and explore further its functions in vasomotion.

Bioassay of endothelium-derived hyperpolarizing factor.

Endothelium-derived hyperpolarizing factor (EDHF) mediates vasodilatation in certain blood vessels, together with prostacyclin and NO. However, its chemical nature is not known. A perfusion-superfusion cascade was developed to confirm the diffusible nature of EDHF. Canine carotid arteries with endothelium were used as donors of vasoactive substances, whereas rings of coronary artery without endothelium were used as detectors. Inhibitors of NO synthesis and cyclooxygenase were present throughout, to avoid interference from NO and prostanoids. Measurements of membrane potential and isometric tension, in coronary arteries without endothelium (used as detectors), demonstrated the release of EDHF from the carotid arteries, following treatment with 8-methoxypsoralen, bradykinin and thimerosal. The K+-channel blocker tetraethylammonium inhibited the action od EDHF in the detectors. Thus, these results demonstrate that endothelial cells release a diffusible activator of K+-channels in vascular smooth muscle.