Recent advances in the study of endothelium-dependent hyperpolarizing factor (EDHF)

Abstract

Recent advances in the properties and physiological functions of endothelium-dependent hyperpolarizing factor (EDHF) in vascular tissues were reviewed briefly. The EDHF-induced hyperpolarization is inhibited by charybdotoxin, indicating that the potential is produced mainly by activation of intermediate conductance Ca-sensitive K-channels. During generation of EDHF responses, endothelial Ca2+ concentration was elevated, suggesting that the activated K-channels were distributed on the endothelial membrane. This was confirmed by direct recording of membrane potentials from endothelial and smooth muscle cells using double patch electrodes. Measurement of the propagation of potentials applied to endothelial or smooth muscle cells to surrounding cells revealed that there were tight electrical connections between endothelial cells much more than between endothelial and smooth muscle cells or between smooth muscle cells, and these observations yielded a possible spread of electrical signal along the endothelial layer first, and then the signals would be conducted to smooth muscle cell layers. These properties of vascular tissues allow speculating that EDHF is an electrical signal propagated from endothelial cells electrotonically through myoendothelial gap junctions. Several candidates have been proposed as EDHF, and possibilities of individual substances for EDHF were discussed. The cellular mechanism of the hyperpolarization-induced vasodilatation remains unclear, and this should be clarified in the future for further understanding of the EDHF-induced vasodilatation.