The EDHFs are vascular relaxation mediators with an important role in tonus control. Studies have proposed that the contribution of EDHFs for vascular relaxation increases in vascular beds and physiopathological conditions in which there is reduced participation of NO. The release of EDHFs may be modulated by binding the agonist to specific receptors and by the shear stress on the blood vessel walls. The EDHFs may act on resistance or conductance arteries, but the vasodilator effect is more pronounced in resistance arteries of humans and experimental models

Estrogen can also regulate vascular relaxation mediated by EDHFs, being one of the possible mechanisms by means of which hormonal treatment exercises a protective effect on the cardiovascular system .Studies have shown reduced hyperpolarization mediated by EDHF in mesenteric bed arterioles of Wistar females submitted to ovariectomy, which was reversed after treatment with 17β-estradiol.

The differences associated with sex in the contribution of EDHFs in resistance artery relaxation have been described in several vascular beds, although opposite effects have been observed. In resistance arteries of the mesenteric bed and other peripheral beds, the release of EDHFs is higher in females than in males