Endothelium-derived hyperpolarizing factor (EDHF) (EDHF)

Endothelium-derived hyperpolarizing factor (EDHF) represents a non-nitric oxide, non-prostacyclin signaling mechanism that mediates endothelium-dependent relaxation of vascular smooth muscle cells (Feletou & Vanhoutte, 2006). It is particularly prominent in small resistance arteries, where it plays a vital role in regulating peripheral vascular resistance and blood pressure (Gutterman et al., 2016). The EDHF response is initiated by an increase in endothelial calcium, which activates small- and intermediate-conductance calcium-activated potassium channels (SKCa and IKCa), leading to endothelial hyperpolarization (Busse et al., 2002). This electrical signal is transmitted to smooth muscle cells via myoendothelial gap junctions or through the release of diffusible factors such as epoxyeicosatrienoic acids (EETs) and hydrogen peroxide (Campbell & Fleming, 2010). Dysfunction of the EDHF pathway is associated with cardiovascular conditions like hypertension, atherosclerosis, and diabetes-related vascular complications (Luksha et al., 2009). Pharmacological targeting of EDHF involves the use of soluble epoxide hydrolase (sEH) inhibitors to prevent the degradation of EETs or the development of potassium channel activators to enhance hyperpolarization (Imig & Hammock, 2009).

Other names

Endothelium-dependent hyperpolarizationEDHEDHF-mediated relaxationNon-NO non-PGI2 vasodilator

The EDHF mechanism involves the activation of endothelial small-conductance (SKCa) and intermediate-conductance (IKCa) calcium-activated potassium channels, which causes endothelial hyperpolarization. This hyperpolarization is then transmitted to the underlying vascular smooth muscle cells via myoendothelial gap junctions or through the release of chemical mediators like epoxyeicosatrienoic acids (EETs), leading to smooth muscle relaxation and vasodilation (Feletou & Vanhoutte, 2006; Gutterman et al., 2016).