Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia.
BACKGROUND
Maternal endothelial dysfunction is a feature of established pre-eclampsia but whether this is a cause or consequence of the disorder is not clear. We tested the hypothesis that endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine (ADMA), the endogenous inhibitor of endothelial nitric oxide synthase, precede and contribute to the development of pre-eclampsia.


METHODS
We assessed uterine artery doppler waveforms in 86 women at 23-25 weeks' gestation. We tested endothelial function in all women using flow-mediated dilation of the brachial artery at 23-25 weeks' gestation. Plasma concentrations of ADMA were also measured.


RESULTS
43 women had normal uterine artery doppler waveforms and subsequently had a normal outcome. The second group of 43 had evidence of impaired placental perfusion and of these, 19 (44%) had normal outcome, 14 (33%) developed intrauterine growth restriction of the fetus (IUGR), and pre-eclampsia arose in ten (23%). Women who developed pre-eclampsia had significantly lower flow-mediated dilation than did women who had normal outcome (3.58% [SD 2.76] vs 8.59% [2.76]; p<0.0001). Irrespective of pregnancy outcome, women with evidence of impaired placental perfusion had significantly higher levels of ADMA than did women with normal doppler waveforms (2.4 micromol/L [IQR 1.97-3.14] vs 0.81 micromol/L [0.49-1.08]; p<0.0001). There was a strong inverse correlation between ADMA and flow-mediated dilation but only in the group of women who eventually developed pre-eclampsia (r=-0.8, p=0.005).


CONCLUSIONS
Maternal endothelial function is impaired in women who eventually develop pre-eclampsia and it occurs before the development of the clinical syndrome. Furthermore, women with high resistance placental circulation at risk of pre-eclampsia, IUGR, or both have raised concentrations of ADMA, which is a potential contributory factor for pre-eclampsia, and is associated with endothelial dysfunction in some women.
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Makrina D
MD
Savvidou
Aroon D
AD
Hingorani
Dimitrios
D
Tsikas
Jürgen C
JC
Frölich
Patrick
P
Vallance
Kypros H
KH
Nicolaides
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001916:Brachial Artery / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D021041:Placental Circulation / Q000502:physiology; D011225:Pre-Eclampsia / Q000097:blood / Q000503:physiopathology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018615:Ultrasonography, Doppler, Color; D016216:Ultrasonography, Prenatal; D014599:Uterus / Q000098:blood supply / Q000000981:diagnostic imaging; D014664:Vasodilation
C018524:N,N-dimethylarginine; D001120:Arginine