Endothelium derived hyperpolarizing factor (EDHF)

Endothelium derived hyperpolarizing factor (EDHF)

Endothelial function has an important role in the normal vasomotion of the blood vessels and endothelial dysfunction is seen in many cardiovascular disorders like hypertension, atherosclerosis and heart failure. Endothelium acts on the vascular smooth muscle through endothelium derived relaxing factors. Endothelium derived hyperpolarising factor (EDHF) is one of the three endothelium-derived relaxing factors (EDRFs), others being nitric oxide and prostacyclin (PGI₂).

EDHF as the name implies, hyperpolarizes the vascular smooth muscle cells, causing them to relax and produce vasodilatation. The action of EDHF involves the calcium sensitive potassium channels (K_Ca). EDHF has been shown to be a major component of endothelium dependent vasodilation resistance arteries of the subcutaneous tissue [1]. Coats P and colleagues felt that nitric oxide and prostacyclin had only a relatively minor role in the vasodilation of subcutaneous resistance arteries.

Existence of EDHF has been proposed as vasodilatory response can occur even when the other two relaxing factors (nitric oxide and prostacyclin) are blocked. Role of EDHF is mainly in the peripheral vascular resistance and organ blood flow. It is thought to be an important factor in regulation of microvascular tone. The exact chemical identity of endothelium derived hyperpolarizing factor is yet to be determined. Endothelium-derived hydrogen sulfide is one potential candidate which acts through calcium ion activated potassium channels K_Ca [2]

Low levels of EDHF have been noted in a study of 57 children with familial Mediterranean fever compared to 31 children as healthy controls. They also had higher levels of C-reactive protein as well as higher systolic and diastolic blood pressures [3].

References

1. Coats P, Johnston F, MacDonald J, McMurray JJ, Hillier C. Endothelium-Derived Hyperpolarizing Factor. Identification and Mechanisms of Action in Human Subcutaneous Resistance Arteries. Circulation. 2001; 103: 1702-1708.
2. Wen JY, Zhang J, Chen S, Chen Y, Zhang Y, Ma ZY, Zhang F, Xie WM, Fan YF, Duan JS, Chen ZW. Endothelium-derived hydrogen sulfide acts as a hyperpolarizing factor and exerts neuroprotective effects via activation of large-conductance Ca²⁺ -activated K⁺ channels. Br J Pharmacol. 2021 Oct;178(20):4155-4175. doi: 10.1111/bph.15607. Epub 2021 Aug 2. PMID: 34216027.
3. Turkmenoglu Y, Guney E, Irdem A, Dursun H. The role of endothelium-derived hyperpolarizing factor in children with familial mediterranean fever. Acta Reumatol Port. 2020 Oct-Dec;45(4):270-277. English. PMID: 33420772.