Pregnancy Downregulates Actin Polymerization and Pressure-Dependent Myogenic Tone in Ovine Uterine Arteries

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2010-11, Vol.56 (5), p.1009-1015
• Main Authors: Xiao, Daliao, Huang, Xiaohui, Yang, Shumei, Longo, Lawrence D, Zhang, Lubo
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Analysis of Variance; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cytochalasin B - pharmacology; Diseases of mother, fetus and pregnancy; Estradiol - pharmacology; Estrogens - pharmacology; Female; Gynecology. Andrology. Obstetrics; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Pregnancy; Pregnancy. Fetus. Placenta; Progesterone - pharmacology; Progestins - pharmacology; Protein Kinase C - metabolism; Sheep; Uterine Artery - drug effects; Uterine Artery - physiology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.110.159137

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 concentrations, followed by a decrease in the diameter at a constant steady-state level of Ca. Cytochalasin B blocked pressure-induced myogenic constrictions without effect on vascular wall Ca 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.