N-acetylcysteine restores nitric oxide-mediated effects in the fetoplacental circulation of preeclamptic patients.
OBJECTIVE
Preeclampsia is associated with an imbalance between oxidants and antioxidants, resulting in reduced effects of the endothelium-derived, relaxing-factor nitric oxide (NO). Antioxidants, like N-acetylcysteine (NAC), remove reactive oxygen species, resulting in an improvement of endothelial function. We aimed to investigate the effect of NAC on the NO-pathway in the human fetoplacental circulation in preeclampsia and control pregnancies.


METHODS
The NO-pathway was investigated by use of the NO-synthase inhibitor L-NAME in an ex vivo cotyledon perfusion model.


RESULTS
At baseline, fetoplacental arterial pressure was comparable in preeclamptic pregnancies (n=8) and control pregnancies (n=8), and increased dose-dependently after L-NAME. The maximal L-NAME-induced rise in fetoplacental arterial pressure was attenuated in preeclamptic versus control pregnancies (20.8 +/- 2.0 mm Hg vs 36.7 +/- 3.5 mm Hg, P<.05). Addition of NAC increased the L-NAME-induced rise in fetoplacental arterial pressure to 36.4 +/- 3.4 mm Hg in preeclampsia pregnancies (P<.05) and to 49.2 +/- 2.6 mm Hg in control pregnancies (P<.05).


CONCLUSIONS
Preeclampsia is associated with a dysfunction of the NO-pathway. N-acetylcysteine increases NO-mediated effects in the fetoplacental circulation in preeclamptic placentas as well as in healthy control placentas.
Department of Pharmacology-Toxicology, University Medical Centre Nijmegen, The Netherlands.
Tanya M
TM
Bisseling
Eva
E
Maria Roes
Maarten T M
MT
Raijmakers
Eric A P
EA
Steegers
Wilbert H M
WH
Peters
Paul
P
Smits
D000111:Acetylcysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D010920:Placenta / Q000187:drug effects* / Q000502:physiology; D021041:Placental Circulation / Q000187:drug effects* / Q000502:physiology; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy
D009569:Nitric Oxide; D000111:Acetylcysteine