Endothelium-derived Hyperpolarizing Factor(s). Does It Exist and What Role Does It Play in the Regulation of Blood Flow?

摘要

Summary. The endothelium is a source of many substances that play important roles in the short- and long-term regulation of the cardiovascular system. In this review we focus on endothelium-derived hyperpolarizing factor, or EDHF. EDHF is often referred to as the "third pathway" as, in addition to nitric oxide (NO) and prostacyclin (PGI2) EDHF seems to play an important role as the "third" endothelium-derived relaxing factor. Considerable debate is on going concerning the nature of EDHF and, indeed, whether a unique molecule even exists. EDHF, by definition, mediates its action by directly, or indirectly, opening K-channels. In most instances the action of EDHF is abolished by the combination of two K-channel toxins, apamin and charybdotoxin; however, the channels that these inhibitors interact with would seem to be located on endothelial rather than vascular smooth muscle cells. The cellular mechanisms whereby EDHF mediates vascular smooth muscle hyperpolarization may involve myo-endothelial gap junctions thus negating the role for a true chemical mediator. Endothelial dysfunction is a common feature of cardiovascular disease, including the cardiovascular dysfunction associated with diabetes, and the role that changes in the nature/function of EDHF play in this process is currently an area of considerable interest. Therapeutic and dietary interventions that restore endothelial function may prove to be of tremendous benefit in the treatment of cardiovascular disease.