- Endothelium-derived hyperpolarizing factor
Endothelium-derived hyperpolarizing factor or EDHF refers to an unknown compound, secreted by endothelial cells, which leads to
nitric oxide- and prostacyclin-independent vasodilationby relaxation of vascular smooth muscle cells.
Discovery of EDHF
Secretion of nitric oxide (NO) or prostacyclin by endothelial cells causes vascular smooth muscle cell relaxation. In experiments in which both NO and prostacyclin production are inhibited, arterioles still continue to dilate if they are stimulated (e.g. by
acetylcholineor bradykinin), causing vasodilationwhich causes blood flow to increase. This observed increase in blood vesseldilation is inhibited by potassiumchannels blockers; therefore this method of vessel dilation relies on an endothelium-dependent hyperpolarization of the smooth muscle cells. This unknown factor(s) secreted by endothelial cells has been termed endothelium-derived hyperpolarizing factor.
Endothelium-derived hyperpolarizing factor vasodilates by causing
hyperpolarizationcite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |location= |year=2005 |pages= |isbn=1-4160-2328-3 |oclc= |doi= Page 480 ] , hence the name.
Although the phenomenon 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 acidderivatives, the epoxyeicosatrienoic acids (EETs), have been found to mediate the vasodilation. These compounds are formed by epoxidationof any one of four double bondsof the arachidonic acid carbon backbone by cytochrome P450epoxygenase enzymes. In addition, in some cases hydrogen peroxidehas been suggested to function as an EDHF in some vascular beds; although the validity of this observation is debated by several groups. Gap junctional coupling between the endothelium and smooth muscle, has also been implicated in EDHF activity in many arteries, whereby 'EDHF' activity may simply be due to the transfer of an EDH, and not to the activity of a Factor "per se".
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