In blood vessels Endothelium-Derived Hyperpolarizing Factor or EDHF is proposed to be a substance and/or electrical signal that is generated or synthesized in and released from the endothelium; its action is to hyperpolarize vascular smooth muscle cells, causing these cells to relax, thus allowing the blood vessel to expand in diameter. Introduction The endothelium maintains vascular homeostasis through the release of active vasodilators. Although nitric oxide (NO) is recognized as the primary factor at level of arteries, increased evidence for the role of another endothelium-derived vasodilator known as endothelium-derived hyperpolarizing factor (EDHF) has accumulated in the last years. Experiments show that when NO and Prostacyclin (Vasodilators) are inhibited there is still another factor causing the vessels to dilate Despite the ongoing debate of its intriguingly variable nature and mechanisms of action, the contribution of EDHF to the endothelium-dependent relaxation is currently appreciated as an important feature of “healthy” endothelium. Since EDHF's contribution is greatest at level of small arteries, the changes in the EDHF action are of critical importance for the regulation of organ blood flow, peripheral vascular resistance, and blood pressure, and in particular when production of NO is compromised. Moreover, depending on the type of cardiovascular disorders altered, EDHF responses may contribute to, or compensate for, endothelial abnormalities associated with pathogenesis of certain diseases. It is widely accepted EDHF plays an important role in vasotone, especially in micro vessels. Its effect varies, depending on the size of the vessel. Pathways Of EDHF There are two general pathways that explain EDH Diffusible factors are endothelium-derived substances that are able to pass through internal elastic layer (IEL), reach underlying vascular smooth muscle cells at a concentration sufficient to activate ion channels, and initiate smooth muscle hyperpolarization and relaxation. Contact-mediated mechanisms bestow endothelial hyperpolarization that passively spreads to the smooth muscle through inter-cellular coupling, and, therefore, EDH is considered as a solely electrical event. Discovering the 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. 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 has been suggested to function