Endothelium-Derived Hyperpolarizing Factor

In blood vessels Endothelium-Derived Hyperpolarizing Factor or EDHF is proposed to be a substance and/or electrical signal that is generated or synthesized in and released from the endothelium; its action is to hyperpolarize vascular smooth muscle cells, causing these cells to relax, thus allowing the blood vessel to expand in diameter.

The endothelium maintains vascular homeostasis through the release of active vasodilators. Although Nitric Oxide (NO) is recognized as the primary factor at level of arteries, increased evidence for the role of another endothelium-derived vasodilator known as endothelium-derived hyperpolarizing factor (EDHF) has accumulated in the last years. Experiments show that when NO and Prostacyclin (Vasodilators) are inhibited there is still another factor causing the vessels to dilate 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 in particular 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 diseases. It is widely accepted EDHF plays an important role in vasotone, especially in micro vessels. Its effect varies, depending on the size of the vessel.

There are two general pathways that explain EDH

Although the phenomenon of EDHF has been observed and reported in scientific literature, to date the chemical identity of the factor(s) has not been determined.

Recently, EDHF has been implicated in gender-related differences in blood pressure control. The generation of animals that lack both Endothelium Nitric Oxide Synthase (eNOS) and COX-1 (Cyclooxygenase-1, a protein that acts as an enzyme to speed up the production of certain chemical messengers), has allowed a direct assessment of the involvement of EDHF to endothelium-dependent relaxation in small arteries. In mice lacking both eNOS and COX-1, EDHF-mediated response appeared to compensate the absence of endothelial NO in females but not in males. In female mice, the deletion of eNOS and COX-1 did not affect mean arterial blood pressure, while males become hypertensive In accordance with this study, EDHF has been suggested to be more important in female arteries to confer endothelium-dependent dilatation, while NO played a predominant role in arteries from males. The latter finding indeed concurs with previous reports in several vascular beds, including mesenteric and tail arteries from rats as well as genital arteries from rabbits. These findings together suggest that under pathological conditions EDHF could compensate for the loss of NO in female rather than in male arteries

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