Systemic Evaluation of Vascular Dysfunction by High-Resolution Sonography in an N x -Nitro- L -Arginine Methyl Ester Hydrochloride – Induced Mouse Model of Preeclampsia-Like Symptoms

Objectives—The purpose of this study was to evaluate vascular function, including arterial resistance and endothelial function, by high-resolution sonography in an Nx- nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced mouse model of preeclampsia-like symptoms. Methods—Pregnant mice were subcutaneously injected with a saline solution (con- trol; n510) or L-NAME (n510) between the 7th and 18th days of gestation. The resistive index and pulsatility index (RI and PI, indicators of arterial resistance) of the uteroplacental, umbilical, femoral, and common carotid arteries and the flow- mediated dilatation (index of endothelial function) of the femoral artery were meas- ured by high-frequency sonography in both groups. Results—We noted significant increases in the RI and PI of the uteroplacental and umbilical arteries and a decrease in the flow-mediated dilatation of the fem- oral artery in the L-NAME group compared with the control group. We also found that the RI and PI of the uteroplacental and umbilical arteries were nega- tively correlated with fetal weight and crown-rump length. The results of the multivariate analysis using a logistic regression model indicated that the flow- mediated dilatation at 120 seconds was an independent diagnostic criterion for the L-NAME-induced preeclampsia-like model. A receiver operating characteristic analysis showed that flow-mediated dilatation at 120 seconds had the greatest area under the curve of 0.934, with an optimal cutoff point of 11.1%, yielding sensitivity of 100% and specificity of 84.6%. Conclusions—The PI and RI of the fetomaternal vasculature can identify fetuses in “high-risk” pregnancies, and flow-mediated dilatation is a reliable indicator for pre- dicting preeclampsia. Assessment of vascular function by high-resolution sonogra- phy provides a useful platform for preeclampsia-related basic research with high reproducibility. Key