Endothelium-derived hyperpolarizing factor and diabetes

Abstract

In addition to its role as a barrier between blood and tissues, the vascular endothelium is responsible for the synthesis and released of a number of vasodilators including prostaglandins, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). As one of these vasodilators, the specific nature of EDHF has not been fully elucidated, although a number of roles have been proposed. Importantly, many conditions, such as hypertension, hyperlipidemia, heart failure, ischemia-reperfusion and diabetes mellitus comprise vascular endothelial dysfunction with EDHF dysregulation. This article reviews reports on the role of EDHF in diabetes-related endothelial dysfunction.

Keywords: Endothelial-dysfunction; Epoxyeicosatrienoic acids; Hydrogen peroxide; Hyperglycemia; Potassium channels.

Figure 1

Endothelium-dependent vasodilation occurs in response to stimuli that induce the endothelial production and/or release of factors that ultimately cause the relaxation of the adjacent vascular smooth muscle. These factors include nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). Depending on the species and vascular bed studied, the nature of the latter has been narrowed to include epoxyeicosatrienoic acids, K⁺ ions, H₂O₂, and the myoendothelial junctions. In diabetes the presence of endothelial dysfunction is mostly characterized by a reduced bioavailability of NO. The effect of diabetes on EDHF is controversial, but a number of studies suggest that EDHF-dependent signaling may be increased therapeutically to ameliorate endothelial dysfunction. ACh: Acetylcholine; AA: Arachidonic acid; NOS: Nitric oxide synthase; COX: Cyclooxygenase; CYP 450: Cytochrome P450.