Pregnancy down‐regulates MLC‐p independent signal pathway in uterine artery

Abstract

Pregnancy is associated with a significant decrease in uterine vascular tone and a striking increase in uterine blood flow that optimize the delivery of oxygen and substrates to the developing fetus via the placenta. We hypothesize that pregnancy attenuates the basal Ca 2+ sensitivity and vascular resistance in the uterine artery through regulation of the myosin light chain phosphorylation (MLC‐p)‐independent pathway. Uterine arteries (UAs) were isolated from nonpregnant and near‐term (~ 140 days gestation) pregnant ewes, and permeabilized with β‐escin and depleted of intracellular Ca 2+ with the calicium ionophore A23187 in tissue bath. Ca 2+ ‐induced contractions and phosphorylation of 20‐kDa myosin light chain were measured simultaneously in the same tissues of isolated permeabilized uterine arteries. Ca 2+ produced time‐dependent increases in the phosphorylation of MLC, which preceded contractions in both nonpregnant and pregnant uterine arteries. Furthermore, Ca 2+ also produced doses‐dependent increases in the MLC‐p of uterine arteries. The levels of MLC‐p were significantly higher in pregnant than those in nonpregnant uterine arteries. However, the ratio of tension/MLC‐p was significantly less in pregnant than that in nonpregnant uterine arteries. These results suggest pregnancy up regulates MLC‐p dependent but down‐regulates its independent signal pathway in regulation of uterine artery contractility.