Effect of nitric oxide deficiency on tissue-type plasminogen activator expression in the umbilical cord in a pregnancy-induced hypertension rat model

Objectives: Our study investigates the effects of nitric oxide (NO) deficiency during pregnancy on coagulation and fibrinolysis balance in fetal circulation.

Main outcome measures: Pregnant rats were treated with or without oral N(G)-nitro-l-arginine methyl ester (L-NAME). Systolic blood pressure (SBP) and urinary protein were measured. On gestational day 20, mRNA levels of tissue-type plasminogen activator (tPA), tissue factor (TF), and TF pathway inhibitor (TFPI) in the umbilical cord, placenta, and maternal aorta were evaluated. Immunohistochemical staining of the placenta for PA inhibitor-1 (PAI-1) was performed.

Results: L-NAME treatment in pregnant rats caused significant SBP elevation and severe proteinuria. In the L-NAME-treated group, weights of fetuses and placentae were diminished. tPA mRNA expression decreased in the umbilical cord and placenta, whereas TF and TFPI mRNA levels did not change. Intense PAI-1 immunoreactivity was observed in a part of degenerated placenta. In the aorta, tPA mRNA expression increased in the L-NAME-treated group, while TFPI mRNA levels were lower than in controls.

Conclusions: NO deficiency during pregnancy decreased tPA mRNA expression in the umbilical cord and placenta but not in the maternal aorta. Imbalance between coagulation and fibrinolysis in fetal and maternal circulations may, at least in part, contribute to fetal growth restriction.