title: S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia.
abstract: OBJECTIVE
  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.
authors.affiliation: Fetal Medicine Department, Rosie Hospital, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 2QQ, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Everett
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: Amita A
authors.initials: AA
authors.lastname: Mahendru
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McEniery
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Garner
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Lees
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011507:Proteinuria / Q000188:drug therapy*; D063177:Pulse Wave Analysis; D026422:S-Nitrosoglutathione / Q000008:administration & dosage / Q000627:therapeutic use*; D016216:Ultrasonography, Prenatal / Q000379:methods; D055815:Young Adult
chemical_list: D020030:Nitric Oxide Donors; D019007:P-Selectin; D026422:S-Nitrosoglutathione
keywords: S-nitrosoglutathione; augmentation index; hypertension; platelets; pregnancy; pulse wave reflection