Endothelium-derived hyperpolarizing factor in the cerebral circulation

Abstract

In cerebral vessels, there is at least one factor or mechanism not involving nitric oxide/endothelium-derived relaxing factor (NO/EDRF) or prostacyclin that is responsible for dilations when endothelial receptors are stimulated. This factor or mechanism is termed endothelium-derived hyperpolarizing factor (EDHF). In rat middle cerebral arteries, branches of the middle cerebral arteries and penetrating arterioles, ATP or UTP elicits the release of EDHF through stimulation of P2Y 2 receptors on the endothelium. The dilations are characterized by the involvement of calcium-activated potassium channels (K Ca) and hyperpolarizations in vascular smooth muscle. In smaller arteries and in arterioles, EDHF appears to be more important than in larger cerebral arteries. Finally, the EDHF response is upregulated 24 h following mild traumatic brain injury (TBI). EDHF may play an important role in the regulation of cerebral blood flow during normal physiological conditions and an even greater role following pathological conditions such as TBI.