Endothelium-derived hyperpolarizing factor in vascular physiology and cardiovascular disease

The endothelium maintains vascular homeostasis through the release of active vasodilators. Although nitric oxide (NO) is recognized as the primary factor at level of conduit arteries, increased evidence for the role of another endothelium-derived vasodilator known as endothelium-derived hyperpolarizing factor (EDHF) has accumulated in the last years. Despite the ongoing debate of its intriguingly variable nature and mechanisms of action, the contribution of EDHF to the endothelium-dependent relaxation is currently appreciated as an important feature of “healthy” endothelium. Since EDHF's contribution is greatest at level of small arteries, the changes in the EDHF action are of critical importance for the regulation of organ blood flow, peripheral vascular resistance and blood pressure, and particularly when production of NO is compromised. Moreover, depending on the type of cardiovascular disorders altered EDHF responses may contribute to, or compensate for endothelial abnormalities associated with pathogenesis of certain disease. Consequently, an identification of vessel-specific nature of EDHF, its modulation of biological activity by selective activators or inhibitors might have a significant impact to our understanding of vascular maintenance in health and disease, and provide basis for novel therapeutic strategies. In this review, the contemporary knowledge about mechanism, function and dysfunction of EDHF-typed responses is systemized. The relevance of this part of endothelium-dependent relaxation for main cardiovascular complications is under discussion. Several issues, like gender differences and role of estrogen for EDHF contribution are summarized for the first time. Authors based on their own experience and data of literature propose several guidelines for future research in the field of EDHF.