The alternative: EDHF

Endothelium-dependent relaxations cannot be fully explained by the release of either NO or/and prostacyclin. Another unidentified substance(s) which h yperpolarizes the underlying vascular smooth muscle cells map contribute to endothelium-dependent relaxations, especially in small arteries. It has be en termed endothelium-derived hyperpolarizing factor (EDHF). In blood vesse ls from various species including humans, endothelium-dependent relaxations are partially or totally resistant to inhibitors of NO synthase and cycloo xygenase and are observed without an increase in the intracellular level of cyclic nucleotides in the vascular smooth muscle cells. In some species (c anine, porcine and human) nitrovasodilators do not cause hyperpolarization while in other (rat, guinea-pig, rabbit), they evoke glibenclamide-sensitiv e hyperpolarization, suggesting the involvement of ATP-dependent potassium channels. In contrast, hyperpolarizations caused by EDHF are insensitive to glibenclamide but are inhibited by apamin or the combination of charybdoto xin plus apamin, indicating that NO and EDHF interact with two different ta rgets. The existence of EDHF as a diffusable substance has been demonstrate d under bioassay conditions whereby the source of EDHF was either native va scular segments or cultured endothelial cells. The identification of EDHF m ap allow a better understanding of its physiological and pathophysiological role(s). (C) 1999 Academic Press.