During the third trimester, fetoplacental and uterine blood flows increase
dramatically to meet the high metabolic demands of the growing fetus. We hy
pothesized that the expression of endothelial nitric oxide synthase (eNOS)
in fetoplacental artery endothelium and the concentrations of nitric oxide
(NO) and cyclic CMP (cGMP) in amniotic fluid (AF) are increased during the
third trimester of ovine gestation. Placental arteries and AF were collecte
d from ewes at 110, 120, 130, and 142 days of gestation (n = 24; mean +/- S
EM term = 145 +/- 3 days). Expression of eNOS protein was measured in intac
t and denuded placental arteries and in endothelium-derived protein by West
ern analysis and confirmed by immunohistochemistry. Concentrations of NO (n
itrates plus nitrites) and cGMP were determined in AF. Placental artery eNO
S protein expression was localized to the endothelium, where it was markedl
y greater than in vascular smooth muscle. Placental artery endothelium-deri
ved eNOS expression and AF cGMP concentrations were similar at 110 and 120
days of gestation; however, both peaked at 130 days at levels two- to three
fold above baseline (P < 0.05) before returning to baseline at 142 days of
pregnancy. The AF NO (nitrates plus nitrites) levels, however, increased pr
ogressively between 120 days of gestation and term (P < 0.05). We concluded
that endothelium-derived placental artery eNOS levels, AF NO (nitrates plu
s nitrites), and AF cGMP were markedly increased during the third trimester
, thus supporting a role for NO-mediated elevations in cGMP in the control
of fetoplacental blood flow.