Pregnancy-specific uterine vascular reactivity: a data-driven computational model of shear-dependent, myogenic, and mechanical radial artery features.

`The entire maternal circulation adapts to pregnancy, and this adaption is particularly extensive in the uterine circulation where the major vessels double in size to facilitate an approximately 15-fold increase in blood supply to this organ over the course of pregnancy. Several factors may play a role in both the remodeling and biomechanical function of the uterine vasculature including the paracrine microenvironment, passive properties of the vessel wall, and active components of vascular function (incorporating the myogenic response and response to shear stress induced by intravascular blood flow). However, the interplay between these factors and how this plays out in an organ-specific manner to induce the extent of remodeling observed in the uterus is not well understood. Here we present an integrated assessment of the uterine radial arteries, likely rate limiters to the flow of oxygenated maternal blood to the placental surface, via computational modeling and pressure myography. We show that uterine radial arteries behave differently to other systemic vessels (higher compliance and shear-mediated constriction) and that their properties change with the adaptation to pregnancy (higher myogenic tone, higher compliance, and ability to tolerate higher flow rates before constricting). Together, this provides a useful tool to improve our understanding of the role of uterine vascular adaptation in normal and abnormal pregnancies and highlights the need for vascular bed-specific investigations of vascular function in health and disease. To our knowledge, this is the first data-driven computational model of autoregulation of uterine radial arteries, likely rate limiters of maternal blood flow to the placenta. The study demonstrates that uterine radial arteries behave differently from systemic vessels (higher compliance, shear-mediated constriction) and change in pregnancy (higher myogenic tone, higher compliance, tolerance of higher flow rates). This pregnancy-specific mathematical model of vascular reactivity allows interrogation of the functional significance of incomplete vascular adaption in pathology.