[Endothelium-derived hyperpolarizing factor (EDHF): potential involvement in the physiology and pathology of blood vessels].

Vascular endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing some vasodilating factors, such as prostacyclin (PGI2), nitric oxide (NO), and a yet unidentified endothelium-derived hyperpolarizing factor (EDHF). Although the nature of EDHF is still controversial, this additional endothelial pathway, endothelium-dependent hyperpolarization, has been demonstrated in many blood vessels of different species, including humans. Despite tissue- and species-specific site differences, endothelium-dependent hyperpolarization plays an important role in the regulation of resistance of vessels and microcirculation. The most probable candidates for EDHF include epoxyeicosatrienoic acids, endothelium-derived potassium ions (K+), and hydrogen peroxide (H2O2). Endothelium-dependent hyperpolarization also probably involves the activation of two populations of endothelial potassium channels, i.e. the small- and intermediate-conductance calcium-activated potassium channels (SKCa and IKCa). Electrical communication between endothelial and smooth muscle cells through gap junctions has also been suggested to be involved in endothelium-dependent hyperpolarization. EDHF-mediated responses are clearly sex-dependent and altered in aging and various pathological conditions, such as hypoxia, hypertension, atherosclerosis, and diabetes, which are mainly related to endothelial dysfunction. Suitable therapeutic treatment can restore these impaired vascular responses. Activating endothelial potassium channels or improving myo-endothelial communication could become interesting therapeutic targets.