S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia

Abstract

Aims: To determine the effects of in vivo S-nitrosoglutathione (GSNO) infusion on cardiovascular function, platelet function, proteinuria and biomarker parameters in early-onset pre-eclampsia.

Methods: We performed an open-label dose-ranging study of GSNO in early-onset pre-eclampsia. Six women underwent GSNO infusion whilst receiving standard therapy. The dose of GSNO was increased incrementally to 100 μg min(-1) whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternal-fetal Doppler parameters were measured at each dose. Platelet P-selectin, protein-to-creatinine ratio and soluble anti-angiogenic factors were measured pre- and postinfusion.

Results: Augmentation index fell at 30 μg min(-1) S-nitrosoglutathione (-6%, 95% confidence interval 0.6 to 13%), a dose that did not affect blood pressure. Platelet P-selectin expression was reduced [mean (interquartile range), 6.3 (4.9-7.6) vs. 4.1 (3.1-5.7)% positive, P = 0.03]. Soluble endoglin levels showed borderline reduction (P = 0.06). There was a borderline significant change in pre-to-postinfusion protein-to-creatinine ratio [mean (interquartile range), 0.37 (0.09-0.82) vs. 0.23 (0.07-0.49) g mmol(-1) , P = 0.06]. Maternal uterine and fetal Doppler pulsatility indices were unchanged.

Conclusions: In early-onset pre-eclampsia, GSNO reduces augmentation index, a biomarker of small vessel tone and pulse wave reflection, prior to affecting blood pressure. Proteinuria and platelet activation are improved at doses that affect blood pressure minimally. These effects of GSNO may be of therapeutic potential in pre-eclampsia, a condition for which no specific treatment exists. Clinical studies of GSNO in early-onset pre-eclampsia will determine whether these findings translate to improvement in maternal and/or fetal outcome.

Keywords: S-nitrosoglutathione; augmentation index; hypertension; platelets; pregnancy; pulse wave reflection.

Figure 1

Changes in the augmentation index adjusted for a standard heart rate of 75 beats min⁻¹ (AIx-75) from baseline with increasing S-nitrosoglutathione (GSNO) dose and 60 min postcessation of infusion. Kruskal–Wallis test, P = 0.002. *Post hoc analysis: P < 0.05 compared with baseline, 6% and –13% at 30 and 100 μg min⁻¹ GSNO, respectively. Graph shows mean values ± interquartile range

Figure 2

Changes in mean arterial blood pressure (MAP) from baseline with increasing GSNO dose and 60 min postcessation of infusion. Kruskal–Wallis test, P = 0.004 *Post hoc analysis: P < 0.05 compared with baseline,19 mmHg. Graph shows mean values ± interquartile range

Figure 3

Platelet surface P-selectin expression pre- and post-GSNO. *Wilcoxon signed-rank test, P = 0.03. Graph shows pre- and post-GSNO values of each participant

Figure 4

Urinary protein-to-creatinine ratio pre- and post-GSNO. Wilcoxon signed-rank test, P = 0.06. Graph shows pre- and post-GSNO values of each participant