Endothelium-derived hyperpolarizing factor and vasodilatation

Properties of endothelium-derived hyperpolarizing factor (EDHF) have been reviewed briefly. The production of EDHF requires an increase in endothelial [Ca2+]i, the properties being similar to those of nitric oxide (NO). EDHF activates K+-channels and hyperpolarizes vascular smooth muscle. The EDHF-induced hyperpolarization is greatly inhibited by charybdotoxin (ChTX) and partially inhibited by apamin, but not by K+-channel inhibitors such as Ba2+, glibenclamide, 4-aminopyridine, suggesting that the K+-channels involved are mainly the Ca2+-sensitive type. Membrane hyperpolarization induces vasodilatation by unidentified mechanisms. Experiments using K+-channel openers and electrophysiology suggest that hyperpolarization may reduce (i) influx of Ca2+ through voltage-sensitive Ca2+-channels, (ii) production of InsP3 in the case of agonist-induced contraction, (iii) Ca2+-sensitivity of contractile elements and (iv) agonist stimulated ion channel activities. In the endothelium-dependent vasodilation, the EDHF/EDRF ratio is larger in peripheral vessels than in the proximal ones, indicating significant importance of EDHF mainly in peripheral arteries. The chemical nature of EDHF remains undetermined, although some candidates such as arachidonic acid metabolites or endogenous cannabinoids are proposed. As the inhibition of gap junctions in artrerial tissues reduces the amplitude of EDHF-induced relaxation, the possible involvement of electrical communication between endothelial and smooth muscle cells has also been considered.