The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia.
OBJECTIVE
To determine the effects of the platelet-specific nitric oxide donor S-nitrosoglutathione on women with severe preeclampsia.


METHODS
Ten women with severe preeclampsia or preeclampsia with severe fetal compromise at 21-33 weeks' gestation each received a 60-90-minute intravenous infusion of 50-250 micrograms/minute of S-nitrosoglutathione. Each was hypertensive, despite conventional oral antihypertensive therapy in eight. Maternal blood pressure, heart rate, platelet activation, uterine artery, and fetal Doppler indices were measured during the infusion.


RESULTS
A dose-dependent reduction in mean arterial pressure from 125 mmHg (95% confidence interval [CI] 117-133) to 103.5 (95% CI 97-111) (P < .005) and an increase in pulse rate from 73.7 beats per minute (95% CI 64.3-84.5) to 89.1 (95% CI 81.2-97.8) (P < .02) was observed during the infusion. Mean uterine artery resistance index fell from 0.76 (95% CI 0.73-0.81) to 0.70 (95% CI 0.65-0.75) (P < .009). Platelet activation measured by P-selectin expression was reduced from 3.02% (95% CI 2.09-4.36) to 1.22% (95% CI 0.94-1.58) (P < .01). Fetal Doppler indices (umbilical artery, middle cerebral artery, and thoracic aorta) showed no significant changes during the infusion.


CONCLUSIONS
S-nitrosoglutathione infusion reduced material mean arterial pressure, platelet activation, and uterine artery resistance without further compromising fetal Doppler indices. This study suggests that platelet-specific nitric oxide donors may prove beneficial in the management of severe preeclampsia.
Lees
C
C
Department of Obstetrics and Gynaecology, King's College School of Medicine and Dentistry, Denmark Hill, London, United Kingdom.
Langford
E
E
Brown
A S
AS
de Belder
A
A
Pickles
A
A
Martin
J F
JF
Campbell
S
S
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009603:Nitroso Compounds / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D026422:S-Nitrosoglutathione; D012720:Severity of Illness Index; D016216:Ultrasonography, Prenatal / Q000187:drug effects*
D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D026422:S-Nitrosoglutathione; D005978:Glutathione