Title:
|
The effects of S-nitrosoglutathione on vascular stiffness and platelet function in early-onset pre-eclampsia
|
Pre-eclampsia is a lead ing cause of maternal and fetal mortality and morbidity.
Early-onset pre-eclampsia occurring before 32 weeks gestation affects ~1% of
pregnancies. At these gestations conservative management focussing on
control of hypertension and seizure prevention, to gain fetal maturity is key.
Impaired nitric oxide bioavailability, is thought to play a major role in the
maternal manifestations of pre-eclampsia such as hypertension and likewise
platelet activation, proteinuria and oedema. There is no current treatment that
targets the underlying pathophysiology.
Uterine artery Doppler and arterial stiffness were assessed in ninety-nine
women, at high a priori risk of pre-eclampsia. The study showed a positive
correlation between increased uterine artery impedance and both pulse wave
reflection (AI)() and aortic pulse wave velocity (aPWV). Alx was negatively
correlated with neonatal birth weight.
Infusion studies of S-nitrosoglutathione (GSNO) and labetalol, the standard
antihypertensive used in pre-eclampsia, were performed in 12 healthy nonpregnant
volunteers to assess the effects on Alx and aPWV and cardiac output.
The study showed that GSNO and labetalol have similar effect on blood
pressure, however GSI\lO, but not labetalol, reduces Alx.
The primary outcome of the GSNO infusion study in preeclampsia was to
establish the dose of GSNO at which there was optimal reduction in Alx, without
causing a clinically significant fall in blood pressure. Secondary outcomes
included the effect on platelet function, soluble biomarkers and proteinuria in
the mother and Doppler parameters in both the mother and fetus. Six women
underwent infusion and an infusion rate of 1O-30mcg/min GSNO was
established as an optimal dose. GSNO significantly reduced platelet activation
and trend towards reduction in proteinuria and soluble endoglin was seen.
The effects of GSNO in women with preeclampsia and make GSNO a promising
candidate for further investigation for the treatment of pre-eclampsia, either as
a sole agent or adjunct to current treatments.
|