Regulation of baseline Ca2+sensitivity in permeabilized uterine arteries: effect of pregnancy

Abstract

The adaptation of contractile mechanisms of the uterine artery to pregnancy is not fully understood. The present study examined the effect of pregnancy on the uterine artery baseline Ca²⁺sensitivity. In β-escin-permeabilized arterial preparations, Ca²⁺-induced concentration-dependent contractions were significantly decreased in uterine arteries from pregnant animals compared with those of nonpregnant animals. Time-course studies showed that Ca²⁺increased phosphorylation of 20-kDa myosin light chain (MLC₂₀), which preceded the tension development in vessels from both pregnant and nonpregnant animals. When compared with vessels from nonpregnant animals, there was a significant increase in the protein level of MLC₂₀and an accordance increase in the level of Ca²⁺-induced phosphorylated MLC₂₀(MLC₂₀-P) in uterine arteries during pregnancy. Simultaneous measurements of MCL₂₀-P levels and contractions stimulated with Ca²⁺in the same tissues demonstrated a significant attenuation in the tension-to-MLC₂₀-P ratio in uterine arteries during pregnancy. Activation of PKC with phorbol 12,13-dibutyrate (PDBu) potentiated Ca²⁺-induced contractions in uterine arteries from nonpregnant but not pregnant animals. Accordingly, inhibition of PKC attenuated Ca²⁺-induced contractions in uterine arteries from nonpregnant but not pregnant animals. PDBu produced contractions in the presence or absence of Ca²⁺in the β-escin-permeabilized arteries, which were significantly decreased in uterine arteries from pregnant compared with nonpregnant animals. The results suggest that pregnancy upregulates the thick-filament regulatory pathway by increasing MLC₂₀phosphorylation but downregulates the thin-filament regulatory pathway by decreasing the contractile sensitivity of MLC₂₀-P, resulting in attenuated baseline Ca²⁺sensitivity in the uterine artery. In addition, PKC plays an important role in the regulation of basal Ca²⁺sensitivity, which is downregulated during pregnancy.