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 acetylcholine or bradykinin), causing vasodilation which causes blood flow to increase. This observed increase in blood vessel dilation is inhibited by potassium channels 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.
Mechanism
Endothelium-derived hyperpolarizing factor vasodilates by causing hyperpolarization[1], hence the name.
Chemical Identity
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 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 cytochromeP450 epoxygenase enzymes. In addition, in some cases hydrogen peroxide has 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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