Analysis of nitric oxide metabolism as a placental or maternal factor underlying the etiology of pre-eclampsia.
BACKGROUND
Defective nitric oxide (NO)-mediated vasodilation is widely regarded as an underlying cause of hypertension in pre-eclampsia, although there are also arguments against this hypothesis.


METHODS
We examined both the mRNA levels and the presence of a Glu298Asp substitution in the NO synthase (NOS) gene, as well as the NO metabolite concentration, in placentas and maternal sera from women with pre-eclampsia and in normotensive pregnant controls (25-40 vs. 24-41 weeks of gestation).


RESULTS
Pre-eclamptic and control placentas did not show any significant differences in their NO metabolite levels or their NOS expression levels as measured by quantitative RT-PCR. In addition, we did not find any association between pre-eclampsia and the occurrence of the Glu298Asp amino acid substitution in the NOS gene. In contrast, high maternal circulating NO metabolites were evident in severe pre-eclampsia (p < 0.0001). Although a positive correlation between circulating NO metabolites and blood pressure was not observed, uterine artery resistance measured by ultrasound was found to positively correlate with the maternal NO levels.


CONCLUSIONS
Our current data suggest that an altered placental NOS pathway is unlikely to be the primary cause of pre-eclampsia and that the activation of this pathway is possibly in response to maternal symptoms.
Department of Obstetrics and Gynecology, Fujita Health University, Toyoake, Japan. nharuki@fujita-hu.ac.jp
Haruki
H
Nishizawa
Kanako
K
Pryor-Koishi
Machiko
M
Suzuki
Takema
T
Kato
Takao
T
Sekiya
Shin
S
Tada
Hiroki
H
Kurahashi
Yasuhiro
Y
Udagawa
D000328:Adult; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D005865:Gestational Age; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010920:Placenta / Q000737:chemistry* / Q000201:enzymology; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000201:enzymology / Q000209:etiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009566:Nitrates; D012333:RNA, Messenger; D001224:Aspartic Acid; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP