Vascular Biology and Microcirculation: Venoarterial communication mediates arterial wall shear stress-induced maternal uterine vascular remodeling during pregnancy

摘要

Although expansive remodeling of the maternal uterine circulation during pregnancy is essential for maintaining uteroplacental perfusion and normal fetal growth, the underlying physiological mechanisms are not well understood. Using a rat model, surgical approaches were used to alter uterine hemodynamics and wall shear stress (WSS) to evaluate the effects of WSS and venoarterial communication (e.g., transfer of placentally derived growth signals from postplacental veins to preplacental arteries) on gestational uterine vascular remodeling. Changes in WSS secondary to ligation of the cervical but not the ovarian end of the main uterine artery and vein provoked significant expansive remodeling at the opposite end of both vessels, but only in pregnant animals. The ≈50% increase in lumen diameter (relative to the contralateral horn) was associated with an upregulation of total endothelial nitric oxide (NO) synthase expression and was abolished by in vivo NO synthase inhibition with N-nitro-l-arginine methyl ester. Complete removal of a venous segment adjacent to the uterine artery to eliminate local venous influences significantly attenuated the WSS-induced remodeling by about one-half (P < 0.05). These findings indicate that, during pregnancy, 1) increased WSS stimulates uterine artery growth via NO signaling and 2) the presence of an adjacent vein is required for arterial remodeling to fully occur.>NEW & NOTEWORTHY This study provides the first in vivo evidence for the importance of venous influences on arterial growth within the uteroplacental circulation.