NOS3 and hypertensive disorder: This finding is consistent with previous studies in eNOS knockout mice, which demonstrated that eNOS is required in pregnancy to maintain uteroplacental vascular remodeling and normal fetal growth.34,35 We now find that specific loss of BH4-mediated eNOS function, termed eNOS coupling is likely to be the major contributor toward vascular dysfunction, inadequate uteroplacental remodeling and hence hypertension observed in pregnant Gch1fl/flTie2cre mice.