In response to various neurohumoral substances en-dothelial cells release nitric oxide (NO) and prostacy-clin, and produce hyperpolarization of the underlying vascular smooth muscle cells, possibly by releasing another factor termed endothelium-derived hyperpolarizing factor (EDHF). NO and prostacyclin stimulate smooth muscle soluble guanylate and adenylate cyclase respectively and can activate, depending on the vascular tissue studied, ATP-sensitive potassium ( KATP) and large conductance calcium-activated potassium channels (BKca). Furthermore, NO directly activates BKca. In contrast to NO and prostacyclin, EDHF-mediated responses are sensitive to the combination of charybdotox-in plus apamin but do not involve KATP or BKca. As hyperpolarization of the endothelial cells is required to observe endothelium-dependent hyperpolarization, an electric coupling through myoendothelial gap junctions may explain the phenomenon. An alternative explanation is that the hyperpolarization of the endothelial cells cau In response to various neurohumoral substances en-d endothelial cells release nitric oxide (NO) and prostacy-clin, and produce hyperpolarization of the underlying vascular smooth muscle cells, possibly by releasing another factor termed endothelium-derived hyperpolarizing factor (EDHF). NO and prostacyclin stimulate smooth muscle soluble guanylate and adenylate cyclase respectively and can activate, depending on the vascular tissue studied, ATP-sensitive potassium (KATP) and large conductance calcium-activated potassium channels (BKca). and prostacyclin, EDHF-mediated responses are sensitive to the combination of charybdotox-in plus apamin but do not involve KATP or BKca. As hyperpolarization of the endothelial cells is required to observe endothelium-dependent hyperpolarization, an electric coupling through myoendothelial gap junctions may explain the phenomenon. An alternative explanation is that the hyperpolarization of the end othelial cells cau