Abstract Body: To demonstrate the relationship between nitric oxide-dependent vasodilation and the expression of several enzymes from L-arginine pathway such as protein arginine N-methyltransferase-1, arginase-2, and nitric oxide synthase 2 -3, the cyclic guanosine monophosphate expression, and their activity in preeclamptic women, we employed a non-invasive technique to compare endothelial vasomotor function in 60 nonpregnant women, 60 healthy pregnant women, 55 preeclamptic women, and 40 pregnant women with essential hypertension. The concentrations of cGMP were measured in samples of platelets from all groups. RNA and protein expression for the enzymes were examined by reverse transcription-polymerase chain reaction and western blot analysis in umbilical vein endothelial cells that previously were isolated from all groups of women. Nitrite/nitrate in plasma levels were measured spectrophotometrically by Griess reaction.
The percentage increase of arterial diameter during reactive hyperemia in nonpregnant women, normal pregnant women, essential hipertensive pregnant women, and preeclamptic women was 7.8 ±2.2%; 16.93 ±2.86%; 9.94 ±1.51% and 6.48 ±1.96% respectively. Vasodilation in preeclampsia and essential hypertensive women was significantly less than that in normal pregnant women. The concentration of platelet cGMP was higher in the normotensive pregnant women than in nonpregnant and essential hypertensive women but did not differ from that in preeclamptic groups. Relative expressions of messenger RNA and protein for eNOS were decreased significantly in preeclamptic and essential hypertension endothelial cells compared with cells from normal pregnancies (P<0.001). Nevertheless, relative messenger RNA for iNOS, Arginase-2, and protein arginine N-methyltransferase-1 was significantly increased in cells from preeclampsia (P<0.001) versus cells from normal pregnancies. Preeclamptic women had significantly higher plasma levels of nitrite/nitrate (49.7 ±7.1 µmol/L) compared with normal pregnant, non-pregnant, and essential hypertensive women (34,2 ±3.1 µmol/L, 29.0 ±8.21 µmol/L, and 17,4 ±2.7 µmol/L respectively).
Our results indicate that reduced NO-dependent vasodilation in preeclampsia may be due to the dysregulated expression and activity of enzymes from L-arginine pathway rather than the reduction of cGMP production. Furthermore, increased production of nitrite/nitrate in preeclampsia might be a redirection of NOS 2 and 3 activities to the peroxinitrite production.