OBJECTIVE - To examine endothelin-1 (ET-1) concentrations longitudinal
ly throughout pregnancy in healthy and insulin-dependent diabetic wome
n and to evaluate the relationship between ET-1 and big ET-1 in normal
pregnancy. RESEARCH DESIGN AND METHODS - Venous blood samples were ob
tained consecutively in gestational weeks 18, 28, and 38 from 40 healt
hy women with uneventful pregnancies and 24 pregnant women with IDDM.
By radioimmunoassay, plasma ET-1 and big ET-1 were analyzed in the hea
lthy women and plasma ET-1 in the diabetic women. RESULTS - In the dia
betic pregnant women, plasma ET-1 levels were significantly higher tha
n in healthy pregnant women during the entire observation period (P <
0.001), but did not change with advancing gestational age. Five of the
diabetic, but none of the healthy pregnant women, developed preeclamp
sia. ET-1 levels did not differ between the diabetic women who develop
ed preeclampsia and those who did not. Plasma ET-1 levels in healthy p
regnant women were within the range of those in healthy nonpregnant wo
men and did not change during pregnancy. The big ET-1 levels increased
and the ET-1/big ET-1 ratio decreased significantly during the observ
ation period. CONCLUSIONS - Plasma ET-1 levels do not change with adva
ncing gestational length. During normal pregnancy, the ET-1/big ET-1 r
atio decrease, indicating a suppressed converting enzyme activity or a
ltered clearance of ET-1. Pregnant women with IDDM have markedly eleva
ted ET-1 levels. Although diabetic women with and without preeclampsia
did not differ with respect to endothelial dysfunction, as reflected
by elevated ET-1 concentration, we cannot exclude that altered endothe
lial function may be of importance for the increased frequency of pree
clampsia in pregnant IDDM patients.