Pregnancy attenuates uterine artery myogenic tone and calcium sensitivity

Little is known about the adaptation of myogenic mechanisms of uterine artery smooth muscle to pregnancy. The present study tested the hypothesis that pregnancy attenuates myogenic tone associated with a decrease in Ca 2+ sensitivity of the contractile process in resistance‐sized uterine arteries (UAs). In pressurized resistance sized UAs from nonpregnant and near‐tern (~140 d gestation) pregnant sheep, we measured vascular diameter (μm) and [Ca 2+ ] i simultaneously as a function of intravascular pressure. Pressure‐induced myogenic tone was regulated through both Ca 2+ mobilization and Ca 2+ sensitivity of the contractile process in the ovine UAs. The myogenic tone in small UAs from pregnant compared with nonpregnant sheep was significantly decreased, which was associated with a decrease in Ca 2+ sensitivity in the UA during pregnancy. Activation of PKC by PDBu induced UA constrict without a changes of Ca 2+ signaling, and inhibition of PKC by calphostin C attenuated the pressure‐induced vascular tone and eliminates the difference of myogenic tone between nonpregnant and pregnant animals. The ERK inhibitor PD098059 had no effect on myogenic tone of nonpregnant UAs, but significantly enhances the myogenic tone in pregnant UAs, which abolished the effect of pregnancy. The results suggest that pregnancy down‐regulates the myogenic tone of UA. The reduced myogenic tone may be caused by an increase in ERK activity and a decrease in PKC signal pathway, which lead to a decrease in Ca 2+ sensitivity of myogenic mechanism in the UA during pregnancy.