Although
nitric oxide (NO) is recognized as the primary
vasodilator derived from vascular endothelium in regulating the vascular tone, another
factor, i.e. the endothelium-derived hyperpolarizing factor (
EDHF), has recently gained much attention and has been demonstrated to participate in vasodilatation in various blood vessels from different species, despite its unidentified nature. Most of the studies were conducted in animals and the knowledge of this factor in the human vasculature is relatively limited. This review attempts to address the relevance of
EDHF-mediated function in humans with the possible identity of
EDHF and mechanisms involved. We consider the human vasculature where
EDHF involvement has been documented including the systemic, coronary, and visceral (gastrointestinal, renal and reproductive) circulation. In these vascular systems,
EDHF plays a role under physiological conditions either as another mechanism or as the "back-up" for NO. Furthermore, the contribution of
EDHF changes under certain physiological conditions, such as ageing and pregnancy. In addition, altered
EDHF function has been suggested in various pathological conditions including
heart diseases,
atherosclerosis,
hypertension, diabetes,
eclampsia,
glaucoma,
chronic renal failure,
erectile dysfunction and
ischemia-reperfusion period during open heart surgery. Pharmacological agents such as
potassium channel openers or
cytochrome P450 metabolites have been used to either protect or recover
EDHF-dependent mechanisms. To further develop new therapeutic strategies that target
EDHF, a better understanding is essential with regard to the function of
EDHF under pathophysiological conditions in humans. Furthermore, the interaction between NO and
EDHF as well as their relative contributions in various conditions are critical.