Endothelium-derived hyperpolarizing factor

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Endothelium-derived hyperpolarizing factor or EDHF refers to an unknown compound, secreted by endothelial cells, which leads to nitric oxide- and prostacyclin-independent vasodilation by relaxation of vascular smooth muscle cells.

[edit] Discovery of EDHF

Secretion of nitric oxide (NO) or prostacyclcin by endothelial cells causes vascular smooth muscle cell relaxation and vasodilation. In experiments in which both NO and prostacyclin production are inhibited, arterioles still continue to dilate if they are stimulated (e.g. by acetylcholine or bradykinin), causing vasodilation which causes blood flow to increase. This observed increase in blood vessel dilation is inhibited by potassium ions; therefore this method of vessel dilation relies on a hyperpolarization of the smooth muscle cells. This unknown factor(s) secreted by endothelial cells has been termed endothelium-derived hyperpolarizing factor.

[edit] Chemical Identity

Although the phenomonena of EDHF has been observed and reported in scientific literature, to date the chemical identity of the factor(s) has not been determined. Although some researchers believe the EDHF is potassium ions, other researchers have shown evidence that an endocannabinoid (anandamide) might be involved by activating the CB1-receptor; although the role of anandamide in EDHF has been discounted, as its action has now been shown to occur via a non-endothelium-dependent mechanism. In some cases, members of a class of arachidonic acid derivatives, the epoxyeicosatrienoic acids (EETs), have been found to mediate the vasodilation. These compounds are formed by epoxidation of any one of four double bonds of the arachidonic acid carbon backbone by cytochrome P450 epoxygenase enzymes. In addition, in some cases hydrogen peroxide may function as an EDHF in some vascular beds. Gap junctional coupling between the endothelium and smooth muscle, has also been implicated in EDHF activity in many arteries.