No compensatory upregulation of placental dimethylarginine dimethylaminohydrolase activity in preeclampsia.
OBJECTIVE
Placental dysfunction of the asymmetric dimethylarginine (ADMA) degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) has been suggested as one of the initiating events in the development of preeclampsia (PE). Our primary aim was to investigate the role of the placenta in the metabolism of ADMA during normal pregnancy and PE.


METHODS
We studied 27 nonpregnant healthy women (C), 15 normotensive pregnant females (P), 16 patients with PE, and 7 patients with the 'hemolysis, elevated liver enzymes and low platelets' syndrome (H).


RESULTS
There were no significant differences between P and PE with respect to fetomaternal gradient of ADMA, placental DDAH activity and placental ADMA content. During the first stage of labour, mean (+/-SD) plasma ADMA (micromol/l) was higher in H (0.69 +/- 0.22; p < 0.05) compared with C (0.44 +/- 0.07), P (0.37 +/- 0.06), and PE (0.40 +/- 0.06). ADMA was significantly associated with laboratory parameters of hepatic and renal function and with clinical parameters, including systolic and diastolic blood pressure, gestational age, birth weight, and placenta weight.


CONCLUSIONS
A compensatory upregulation of placental DDAH activity is absent in patients suffering from PE and levels of ADMA in plasma and placenta are normal in patients suffering from PE. However, when the course of PE deteriorates and organ dysfunction (especially liver and kidney) becomes involved, such as during the hemolysis, elevated liver enzymes and low platelets syndrome, ADMA levels increase.
Siroen
Michiel P C
MP
Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Teerlink
Tom
T
Bolte
Antoinette C
AC
van Elburg
Ruurd M
RM
Richir
Milan C
MC
Nijveldt
Robert J
RJ
van der Hoven
Ben
B
van Leeuwen
Paul A M
PA
D000328:Adult; D000581:Amidohydrolases / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D017359:HELLP Syndrome / Q000097:blood / Q000503:physiopathology; D006801:Humans; D009426:Netherlands / Q000453:epidemiology; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000097:blood* / Q000503:physiopathology; D011247:Pregnancy / Q000097:blood* / Q000502:physiology; D011446:Prospective Studies; D015854:Up-Regulation
D000581:Amidohydrolases; C059999:dimethylargininase