Does nitric oxide play a role in the aetiology of pre-eclampsia?

Although progress has been made toward our understanding of the pathophysiology of pre-eclampsia, the precise aetiology of this disease still remains an enigma. One of the hallmarks of pre-eclampsia is a failure of the extravillous cytotrophoblast cells to invade and remodel the uterine spiral arterioles during the first trimester of pregnancy. Moreover, studies suggest that the cause of this disorder may be immunological in nature. Evidence is provided here suggesting that impaired trophoblastic invasion of the spiral arterioles may be linked to the altered immunological response associated with pre-eclampsia. Previous studies by Reister et al., 1999 demonstrated a direct relationship between macrophage infiltration of the myometrial segments of spiral arterioles and reduced trophoblastic invasion in pre-eclampsia. Also, it is well established that activated macrophages produce large amounts of nitric oxide (NO). Our present findings reveal that low concentrations of NO-mimetic drugs (glyceryl trinitrate and sodium nitroprusside) inhibit the ability of trophoblast cells to penetrate through reconstituted extracellular matrix (Matrigel). This inhibition is accompanied by a reduced expression of the cell surface urokinase receptor, a molecule important for invasion. These results suggest a possible mechanistic link between the aberrant macrophage infiltration associated with pre-eclampsia, and the maladapted uteroplacental arterioles that characterize the disease.