title: Pregnancy downregulates actin polymerization and pressure-dependent myogenic tone in ovine uterine arteries.
abstract: Pregnancy is associated with significantly decreased uterine vascular tone and increased uterine blood flow. The present study tested the hypothesis that the downregulation of actin polymerization plays a key role in reduced vascular tone of uterine arteries in the pregnant state. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Activation of protein kinase C significantly increased the filamentous:globular actin ratio and contractions in the uterine arteries, which were inhibited by an actin polymerization inhibitor cytochalasin B. The basal levels of filamentous:globular actin were significantly higher in nonpregnant uterine arteries than those in near-term pregnant sheep. Prolonged treatment (48 hours) of nonpregnant sheep with 17β-estradiol (0.3 nmol/L) and progesterone (100.0 nmol/L) caused a significant decrease in the filamentous:globular actin. In accordance, the treatment of near-term pregnant sheep for 48 hours with an estrogen antagonist ICI 182 780 (10.0 μmol/L) and progesterone antagonist RU 486 (1.0 μmol/L) significantly increased the levels of filamentous:globular actin. Increased intraluminal pressure from 20 to 100 mm Hg resulted in an initial increase in uterine arterial diameter and vascular wall Ca(2+) concentrations, followed by a decrease in the diameter at a constant steady-state level of Ca(2+). Cytochalasin B blocked pressure-induced myogenic constrictions without effect on vascular wall Ca(2+) levels and eliminated the differences in pressure-dependent myogenic tone between nonpregnant sheep and near-term pregnant sheep. The results indicate a key role of actin polymerization in protein kinase C-induced myogenic contractions and suggest a novel mechanism of sex steroid hormone-mediated downregulation of actin polymerization underlying the decreased myogenic tone of uterine arteries in pregnancy.
authors.affiliation: Center for Perinatal Biology, Department of Physiology and Pharmacology, 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: Shumei
authors.initials: S
authors.lastname: Yang
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012756:Sheep; D055988:Uterine Artery / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D004967:Estrogens; D011372:Progestins; D003571:Cytochalasin B; D011374:Progesterone; D004958:Estradiol; D011493:Protein Kinase C