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S ‐Nitrosoglutathione improves haemodynamics in early‐onset pre‐eclampsia
Author(s) -
Everett Thomas R.,
Wilkinson Ian B.,
Mahendru Amita A.,
McEniery Carmel M.,
Garner Stephen F.,
Goodall Alison H.,
Lees Christoph C.
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12379
Subject(s) - interquartile range , medicine , blood pressure , creatinine , eclampsia , placental growth factor , pulse wave velocity , endocrinology , urology , cardiology , pregnancy , genetics , vascular endothelial growth factor , vegf receptors , biology
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 D oppler 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 D oppler 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.