EDHFs

EDHFs refers to endothelium-derived hyperpolarizing factors, a collective term for mechanisms and mediators that cause hyperpolarization of vascular smooth muscle and subsequent vasodilation. EDHF responses occur when the endothelium prompts smooth muscle to hyperpolarize independently of, or in addition to, nitric oxide and prostacyclin pathways, contributing to regulation of microvascular tone.

The underlying processes are diverse. Endothelial cells can trigger hyperpolarization of neighboring smooth muscle cells through electrical coupling via gap junctions and by releasing factors that activate smooth muscle potassium channels, notably small and intermediate conductance calcium-activated K+ channels. The result is closure of voltage-gated calcium channels in smooth muscle and relaxation. This hyperpolarization can spread along the vessel wall through intercellular coupling, reinforcing vasodilation.

Key mediators proposed for EDHF-type responses include cytochrome P450 epoxygenase products such as epoxyeicosatrienoic acids (EETs), hydrogen peroxide in certain vessels, and potassium ions released by the endothelium that act on smooth muscle receptors. The relative contribution of these mediators varies by vessel type, species, and experimental conditions, reflecting a spectrum rather than a single molecule.

Physiological relevance and disease. EDHF-mediated vasodilation is particularly important in small resistance arteries that determine tissue perfusion. Its prominence can shift with age, vascular bed, and disease states; for example, some forms of hypertension or diabetes can alter EDHF signaling. Understanding EDHF is thus essential for a complete picture of endothelial function and microvascular regulation.