Hypertension and Nitric Oxide in Pre-eclampsia

초록

Preeclampsia (PE) is a multi-system disease of pregnancy with an incidence of 5%？7% among the general population. It involves hypertension, proteinuria, edema, abnormal clotting, fetal growth restriction, and premature birth in the third trimester of human pregnancy, all of which can be associated with vascular endothelial dysfunction. Endothelial dysfunction induces hypertension in PE via a decrease in the release of nitric oxide (NO), because endothelial NO plays an important role in the vascular system during pregnancy, in neutrophil activation and in the increase of vasoconstrictors such as endothelin-1 and thromboxane A2 (TXA2). However, NO synthesized by peripheral non-adrenergic non-cholinergic (NANC) nerves distributed in the blood vessels is also involved in vasodilatation. Therefore, in the present study, the activity, expression and modulation of neuronal NO synthase (nNOS), which mediates NO release in the NANC nerves, were examined in a human placenta and two placental full-term trophoblast cell lines (HT-1 and TL-1). Particularly, trophoblasts distributed in the placenta also produce NO constitutively by eNOS or nNOS, or both. Trophoblast-derived NO prevents platelet and leukocyte adhesion, and controls vascular tone. Therefore, impairment of the NO release mediated by placental trophoblasts and endothelial cells may be associated with several systems in PE. Here, we demonstrate new findings that NO release can be impaired by the decreased nNOS expression, the phosphorylated nNOS, and/or the altered interactions with caveolin proteins in hypertensive patients with PE, and also that detrimental effects of inflammatory cytokines induced in PE can cause these pathological results.