Endothelium-derived hyperpolarizing factor

Abstract

Endothelial cells respond to various neurohumoral substances by synthesizing and releasing various vasodilators including nitric oxide (NO), prostacyclin and another unidentified substance(s) that hyperpolarizes the underlying vascular smooth muscle cells. This substance has been termed endothelium-derived hyperpolarizing factor (EDHF). EDHF may play a significant role in the local regulation of peripheral vascular resistance and thus in the distribution of blood flow. Indeed, in both animals and humans, the contribution of EDHF responses is significantly greater in smaller than in larger arteries. The identity of EDHF remains elusive. Whether or not EDHF is an epoxyeicosatrienoic acid, derived from the cytochrome P450 monooxygenase, is still a matter of debate. In aging animals and in animal models of vascular diseases such as hypertension, diabetes and endotoxemia, endothelium-dependent hyperpolarizations are diminished. The limited number of observations permits a similar conclusion in humans. The absence of endothelium-dependent hyperpolarization may contribute to the abnormal vascular responses observed under these pathologic conditions. Conversely, enhancement of EDHF-mediated responses contributes to the antihypertensive and cardioprotective action of drugs such as angiotensin- converting enzyme inhibitors and estrogens and of diets rich in ω3- unsaturated fatty acids and exercise training. The identification of the chemical structure of EDHF, of its endothelial biosynthetic pathway and of its exact target on smooth muscle cells will provide new perspectives in cardiovascular drug research.