title: 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 beta-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 MLC20 and 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 beta-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 MLC20 phosphorylation 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.
authors.affiliation: Department of Physiology and Pharmacology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
authors.forename: Daliao
authors.initials: D
authors.lastname: Xiao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.forename: William J
authors.initials: WJ
authors.lastname: Pearce
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D021041:Placental Circulation / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D013314:Stress, Mechanical; D014599:Uterus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology
chemical_list: D018994:Myosin Light Chains; D002118:Calcium