Role of endothelium-derived hyperpolarizing factor in endothelial dysfunction during diabetes.

1. Under normal conditions, the endothelium plays a major role in the maintenance of vasodilatory tone via the production of endothelium-derived vasodilator agents, such as prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). Inhibition of endothelium-dependent relaxation features prominently in a range of cardiovascular diseases, including hypertension, coronary artery disease and diabetes. 2. Endothelium-derived hyperpolarizing factor is a prominent vasodilator, particularly in smaller arteries and arterioles. There is now emerging evidence to suggest that EDHF may play a role in the endothelial dysfunction in diabetes. 3. Since the first description of endothelium-dependent hyperpolarization some 20 years ago, it has emerged that EDHF is heterogeneous in nature, consisting of diffusible factors and contact-mediated mechanisms. The specific identity of EDHF in any particular vascular bed may influence the impact of diabetes on vascular function. 4. There is accumulating evidence in diabetic rat models and humans showing impaired EDHF activity in small resistance vessels. In contrast, studies in mice suggest that EDHF activity is actually enhanced under diabetic conditions. 5. It is clear that alterations in EDHF activity may have an important contribution in diabetes, more specifically in contributing to microvascular complications observed under diabetic conditions.