Estrogen induces vascular wall dilation -: Mediation through kinase signaling to nitric oxide and estrogen receptors α and β

Estrogen has been shown to affect vascular cell and arterial function in vitro and in vivo. Here we examined the ability of estradiol (E-2) to cause rapid arterial dilation of elastic and muscular arteries in vivo and the mechanisms involved. E-2 administration caused a rapid increase in the outer wall diameter of both types of arteries in ovariectomized female mice. This resulted from estrogen receptor (ER)- mediated stimulation of nitric oxide production, demonstrated by preinjecting the mice arteries with a soluble inhibitor of nitric oxide ( monomethyl L-arginine) and by showing the absence of E-2 action in eNOS-/- mice. Rapid activation of both ERK/MAP kinase and phosphatidylinositol 3-kinase activity was found in the E-2-exposed arteries, and inhibiting either kinase prevented the vasodilatory action of E-2. Kinase activation and vasodilator responses to E-2 were absent in either ER alpha or ER beta knock-out mice, implicating both receptor subtypes as mediating this E-2 action. These results indicate that E-2 modulation of arterial tonus through plasma membrane ER and rapid signaling could underlie many previously observed actions of estrogen reported to occur in women.