Figure 2.

Estrogen plays a pivotal role in regulating functional adaptation of uteroplacental vessels in pregnancy. 17β-Estradiol (E₂β) upregulates RYR2 and KCNMB1 expression and ryanodine receptor 2 (RyR₂) and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel activity and subsequently enhances Ca²⁺ spark/STOC coupling, leading to reduced uterine arterial myogenic tone. E₂β also increases production/release of nitric oxide (NO), hydrogen sulfide (H₂S) and prostacyclin (PGI₂) via upregulating the expression of NOS3, CBS and COX1 in uterine arteries. These vasodilators, through receptor or nonreceptor mechanisms to activate protein kinase A (PKA) and protein kinase G (PKG), promote vasodilation and blunt vasoconstriction, resulting in an overall decrease in uterine vascular tone.