Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia

Pre-eclampsia is a principal cause of maternal morbidity and mortality, aff ecting 5-10% of first pregnancies worldwide. Manifestations include increas ed blood pressure, proteinuria, coagulopathy and peripheral and cerebral oe dema. Although the aetiology and pathogenesis remain to be elucidated, the placenta is undoubtedly involved, as termination of pregnancy eradicates th e disease. Here we have cloned a complementary DNA from human placental mes senger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB)(1) of other mammalian species. In female rats, concentrations of NKB several-fol d above that of an animal 20 days into pregnancy caused substantial pressor activity. In human pregnancy, the expression of NKB was confined to the ou ter syncytiotrophoblast of the placenta, significant concentrations of NKB could be detected in plasma as early as week 9, and plasma concentrations o f NKB were grossly elevated in pregnancy-induced hypertension and pre-eclam psia. We conclude that elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia, and that treatment with certai n neurokinin receptor antagonists may be useful in alleviating the symptoms .