Estrogen induces vascular wall dilation: mediation through kinase signaling to nitric oxide and estrogen receptors alpha and beta.
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 ERalpha or ERbeta 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.
Guo
Xiaomei
X
Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Razandi
Mahnaz
M
Pedram
Ali
A
Kassab
Ghassan
G
Levin
Ellis R
ER
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019869:Phosphatidylinositol 3-Kinases