Expression of nitric oxide synthase in normal and preeclamptic placental tissue and effects of glyceryl trinitrate and shear stress on placental blood flow.

BACKGROUND: To study the expression of constitutively expressed nitric oxide synthase (cNOS) as well as the effects of glyceryl trinitrate (GTN) and shear stress on normal and preeclamptic placental tissue. METHODS: The expression of cNOS was studied using NADPH diaphorase activity reaction in seven normal and four preeclamptic placentas. The effect of GTN (n = 5) and shear stress induced by increasing the flow rate in the perfusion system (n = 5) was studied using an in vitro placental perfusion method. RESULTS: No difference in the distribution of cNOS in placental tissue was found between preeclamptic and normal pregnancies. Shear stress did not affect the production of nitric oxide metabolites. GTN was able to dilate placental vasculature. CONCLUSIONS: cNOS derived from syncytiotrophoblasts may not contribute to the development of preeclampsia. Placental vasculature responds to nitric oxide by vasodilation.

The effect of vitamin C and E on placental lipid peroxidation and antioxidative enzymes in perfused placenta.

BACKGROUND: To investigate placental lipid peroxidation products and antioxidative enzymes after vitamin C and/or E infusions into the maternal circulation of normal and preeclamptic placentas perfused in vitro. METHODS: Placentas from 29 normal and six preeclamptic women delivered between 27 and 41 weeks of gestation were used in the study. RESULTS: Neither vitamin C (500 microM) nor vitamin E (50 microM) had any effect on placental lipid peroxidation or antioxidative enzymes in normal placentas. Vitamin C infused in preeclamptic placentas decreased peroxidation potential, as an indicator of lipid peroxidation to the same level it was in normal placentas (812 vs. 649 mV/mgprot; p=0.420). The activity of superoxide dismutase (SOD) was lower (1350 vs. 2030 ng/mgprot; p=0.023) in preeclamptic placentas, and the activities of glutathione peroxidase (0.22 vs. 0.08 micromol/min x mgprot; p=0.010) and glutathione-S-transferase (19.8 vs. 13.1 micromol/min x mgprot; p=0.016) were higher in preeclamptic compared to normal placentas. CONCLUSION: In this study, based on in vitro perfused normal and preeclamptic placentas, exogenous antioxidative vitamins had no effect on lipid peroxidation or endogenous antioxidative enzymes in normal placenta, but reduced placental lipid peroxidation and could potentiate the activity of some endogenous placental antioxidative enzymes in preeclamptic placenta.

Lipid peroxidation and antioxidants in normal and pre-eclamptic pregnancies.

Lipid peroxidation has been suggested as a pathogenetic factor of pre-eclampsia. In this study we measured lipid peroxidation products and the counteracting antioxidant functions in maternal serum and placental tissue in normal pregnancy and pre-eclampsia. Placentae and maternal serum from 15 normal and 15 pre-eclamptic pregnancies were collected. Lipid peroxidation was measured as peroxidation potential, thiobarbituric acid reacting substances (TBARS) and conjugated diene onuble bonds. The antioxidative capacity was measured as the activity of superoxide dismutase, glucose 6-phosphate-dehydrogenase, glutathione peroxidase and glutathione transferase and the concentration of placental vitamin E. Placental lipid peroxidation was higher in pre-eclampsia than in normal pregnancy, when measured by peroxidation potential and TBARS (P = 0.002 and P = 0.027, respectively). The activity of placental superoxide dismutase (P = 0.003) and glucose 6-phosphate-dehydrogenase (P = 0.019) was significantly lower in pre-eclampsia than in normal pregnancy. There were no significant differences in the activity of glutathione peroxidase, glutathione-S-transferase or vitamin E level between the study groups. The peroxyl radical trapping capacity (TRAP) was higher (P = 0.013) in the serum of pre-eclamptic than control patients. Lipid peroxidation is increased and the activity of antioxidant enzymes superoxide dismutase and glucose 6-phosphate-dehydrogenase are decreased in pre-eclamptic placenta. The TRAP is high in the serum of pre-eclamptic patients.

Elevated serum group II phospholipase A2 levels are associated with decreased blood flow velocity in the umbilical artery.

Twenty-two hospitalized patients, diagnosed as having hypertensive disorder of pregnancy, were selected from two University Clinics. Maternal serum samples were analyzed for serum group II phospholipase A2 (PLA2-II) by time-resolved fluoroimmunoassay. At the same time, umbilical artery blood flow velocities were measured with color Doppler sonography for orientation and pulsatile Doppler sonography for recording waveforms. Nineteen normotensive third-trimester pregnant patients served as a control group. Maternal serum PLA2-II was elevated in 8 cases with preeclampsia. This elevation was invariably associated with decreased blood flow velocity in the umbilical artery. In 1 case, the clinical condition allowed simultaneous follow-up of serum enzyme and blood flow velocity: a further rise of serum PLA2-II was linked to a further decrease in the blood flow velocity of the umbilical artery. A large spillover of the elevated PLA2-II content from the preeclamptic placenta into the maternal serum is associated with a decrease in blood flow velocity in the umbilical artery. The enzyme might serve as a link between local proximal (placenta) and systemic distal (umbilical arterial blood flow) effectors.

Responses of placental steroids, prostacyclin and thromboxane A2 to thermal stress during pregnancy.

The effect of heat stress on plasma prostacyclin and thromboxane A2 and serum estradiol, estriol and progesterone responses was studied in pregnant and non-pregnant women. Group I consisted of 15 healthy non-pregnant women, group II of 23 women 13-14 weeks pregnant, and group III of 23 women 36-37 weeks pregnant. Blood samples were taken before the heat stress, at the end of the stress (70 degrees C for 20 min) and 20 min and/or 45 min after the end of stress. The rectal temperature increased 0.3-0.4 degrees C. The concentration of progesterone did not change during the experiment but that of estradiol increased by 11% (P less than 0.005) in group II and by 10% (P less than 0.01) in group III after the end of the stress. Estriol increased only in group III (by 12%, P less than 0.005) after the end of the stress and the increase was higher as compared to group II (P less than 0.005). The metabolite of prostacyclin increased only in group III by 15% (P less than 0.05) during the heat stress. The metabolite of thromboxane A2 decreased in group II by 20% (P less than 0.005) at the end of the stress while there was no change in group III. The fetal heart rate reactivity remained unchanged and only few uterine contractions were recorded. The small changes found in the levels of prostanoids and placental steroids in response to heat stress do not seem to have any deleterious effects on fetal well-being. The slightly increased concentration of placental steroids may rather reflect changes in metabolism than an increase in uteroplacental blood flow.

Haemodynamic response to moderate thermal stress in pregnancy.

The effect of a moderate heat stress on cardiovascular responses was studied: group I consisted of 15 healthy non-pregnant women, group II of 23 women 13-14 weeks pregnant and group III of 23 women 36-37 weeks pregnant. Heart rate, stroke volume, cardiac output, arterial blood pressure and peripheral vascular resistance were recorded every 5-10 minutes during a resting period (20 min, 21-23 degrees C) followed by heat stress (20 min, 70 degrees C, 15% relative humidity) and a recovery period (45 min, 21--23 degrees C). The rectal temperature increased 0.3-0.4 degrees C in each group during thermal stress. The heart rate before stress was highest in the advanced pregnancy group but increased almost identically in each group by 36--37 beats per minute during stress and approached starting values during recovery. There were no major changes in stroke volume during the experiment in any group nor were there any differences between the three groups. Arterial blood pressure did not change significantly in any group during the experiment; the differences between the groups were minimal. Peripheral vascular resistance began to fall at the start of the thermal stress and returned to prestress levels at the end of the recovery period. There were no differences between the groups in proportional changes of peripheral resistance. We conclude that pregnancy does not alter the cardiovascular responses to moderate thermal stress.