NOS2 and preeclampsia: Importantly, further studies are warranted to examine better the differences between the endothelial NO synthase-derived NO and the inducible NO synthase-derived NO in the placenta because there is evidence that during normal placental development occurs up-regulation of endothelial NO synthase, which seems to be impaired in placental growth restriction of preeclampsia, while inducible NO synthase is down-regulated in the placenta of normal pregnancy but may be up-regulated in the RUPP model of preeclampsia [46,48].