Nitric oxide donors in pregnancy: fetomaternal hemodynamic effects induced in mild pre-eclampsia and threatened preterm labor.
OBJECTIVE
The present study was performed to determine whether there are significant differences in the effects of the nitric oxide donor, glyceryl trinitrate, administration in pregnancies complicated by mild pre-eclampsia compared to the effects in pregnancies which are uncomplicated by this pathology. Glyceryl trinitrate is able to release nitric oxide (NO); deficiency of NO has been hypothesized in the pathogenesis of pre-eclamptic disorders.


METHODS
In this prospective study, ten patients with threatened preterm labor and ten patients with mild preeclampsia were studied at around 30 weeks of pregnancy. The maternal blood pressure, maternal heart rate, fetal heart rate and flow velocity waveforms of the placental uterine artery, umbilical artery and fetal middle cerebral artery, evaluated by means of color Doppler and pulsed Doppler, were recorded before and 10, 20 and 30 min after the sublingual administration of 0.3 mg of glyceryl trinitrate or placebo. The pulsatility index (PI) was calculated. The percentage change from the control period (delta %) was calculated for each parameter at 10, 20 and 30 min. Ten normal pregnant women at the same gestational age were used as controls and were administered a placebo.


RESULTS
The maternal blood pressure recorded as systolic and diastolic values, demonstrated a significant decrease in the pre-eclampsia group after glyceryl trinitrate administration; the delta % at any time considered was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the placental uterine artery showed a significant decrease in both groups after 20 and 30 min from drug administration; the delta % at 20 and 30 min was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the umbilical artery showed a significant decrease after 30 min from the glyceryl trinitrate administration. The fetal heart rate showed no significant variations during the study in either group. The PI of the fetal middle cerebral artery showed no significant variations during the study in either group. No parameter was changed in the control group.


CONCLUSIONS
Glyceryl trinitrate administration was followed by a greater reduction of the resistance to blood flow in the fetoplacental circulation of the pregnancies affected by mild pre-eclampsia compared to pregnancies uncomplicated by this pathology. This effect can be attributed to the NO released by the drug which offsets the decreased production of NO, postulated to contribute to the pathogenesis of pre-eclampsia.
Luzi
G
G
Department of Obstetrics, Gynecology and Pediatrics, University of Perugia, Italy.
Caserta
G
G
Iammarino
G
G
Clerici
G
G
Di Renzo
G C
GC
D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006340:Heart Rate, Fetal / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000196:embryology; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000008:administration & dosage; D007752:Obstetric Labor, Premature / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply; D010925:Placental Function Tests; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D018615:Ultrasonography, Doppler, Color; D016216:Ultrasonography, Prenatal; D014469:Umbilical Arteries / Q000000981:diagnostic imaging; D014599:Uterus / Q000098:blood supply; D014665:Vasodilator Agents / Q000008:administration & dosage
D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin