Placental Nitric Oxide Production and Umbilical Artery Vascular Impedance in Early Pregnancy

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Abstract
Objective: To evaluate whether the vasorelaxant molecule nitric oxide (NO) and its second messenger cyclic guanosine monophosphate (cGMP) modulate the reduction in resistance within the fetoplacental circulation that occurs during the first trimester of pregnancy. Methods: We studied 27 women undergoing termination of pregnancy for psychosocial indications between 9 and 15 weeks’ gestation. Each had ultrasound dating of the fetus and Doppler umbilical artery (UA) flow investigation immediately before the operation. Placental tissue was assayed for nitric oxide synthase (NOS) activity and cGMP content. Results: Both UA pulsatility index (PI) and placental endothelial NOS activity decreased significantly with advancing gestation (r = –.52 and –.41, respectively). Umbilical PI correlated positively with endothelial NOS activity and cGMP level. Multiple linear regression analysis indicated that cGMP contributed most strongly to UA PI (P < .001). Conclusion: Our findings suggest somewhat paradoxically that NOS activity and cGMP levels are highest in the early gestations, when umbilical PI is also high, and decrease as umbilical PI decreases. Further studies are required to determine whether the predominant effect of NO is that of a vascular relaxant or a modulator of new villous vessel formation.

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