Shear stress regulation of nitric oxide production in uterine and placental artery endothelial cells: experimental studies and hemodynamic models of shear stresses on endothelial cells
Review | Published: 23 October 2009
Benjamin Sprague1,2, Naomi C. Chesler1 and Ronald R. Magness*,2,3,4
1Dept. of Biomedical Engineering, University of Wisconsin-Madison, 2Dept. of Obstetrics and Gynecology, Perinatal Research Laboratories 3Dept. of Pediatrics and 4Dept of Animal Sciences, Madison USA
Hemodynamic shear stress is the most powerful physiological regulator of endothelial Nitric Oxide Synthase (eNOS), leading to rapid rises in nitric oxide (NO). The substantial increases in uterine and placental blood flows throughout gestation rely heavily on the action of NO. We and others have investigated endothelial function in response to shear stress with cell culture models of shear stress. In order to apply the results of these studies more effectively, we need a more complete understanding of the origin and coupling of the hemodynamic forces and vascular tissue behavior. For example, equations commonly used to calculate in vivo shear stress incorporate assumptions of steady (non-pulsatile) blood flow and constant viscosity of blood (Newtonian fluid). Using computational models, we can estimate a waveform of shear stress over a cardiac cycle and the change in blood viscosity with shear rate and hematocrit levels, two variables that often change with size of vessel and location within a vascular tree. This review discusses hemodynamics as they apply to blood flow in vessels, in the hope that an integration of these fields can lead to improved in vitro shear stress experiments and understanding of NO production in uterine and placental vascular physiology during gestation.