Relationships between plasma endothelin and prostacyclin in normal and preeclamptic pregnancy

Objective: This study aimed to examine the relationships between plasma endothelial 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha) and other biochemical variables in normal pregnancy, preeclampsia, and the nonpregnant state using multiple regression analysis. Methods: Plasma endothelin 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha) were measured after extraction by specific radioimmunoassays in 20 women with proteinuric preeclampsia and 28 normal pregnant women. The two pregnant groups were matched with each other for age and gestation before delivery, and for age with a group of nonpregnant women. Multiple regression analysis was used to create models for plasma endothelin 1 and 2,3-dinor-6-keto-PGF(1 alpha) in the preeclamptic and normal pregnant groups and in the nonpregnant group. Results: Using plasma endothelin 1 as the dependent variable, a significantly negative correlation was found with urinary 2,3-dinor-6-keto-PGF(1 alpha) and plasma albumin in the preeclamptic group, accounting for 53% of the variance in plasma endothelin. The same model in the normal pregnant group showed only plasma albumin to be significantly negatively correlated with plasma endothelin, and the model accounted for only 13% of the variance in plasma endothelin. Using urinary 2,3-dinor-6-keto-PGF(1 alpha) as the dependent variable, an independent negative association was found with plasma endothelin 1 and a positive association with creatinine clearance in the preeclamptic group, accounting for 42% of the variance in urinary 2,3-dinor-6-keto-PGF(1 alpha). Using the same model, neither creatinine clearance nor plasma endothelin was a significant predictor of urinary 2,3-dinor-6-keto-PGF(1 alpha) in normal pregnancy. In the nonpregnant group a negative association was again seen between plasma endothelin 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha). The inverse relationship between plasma endothelin 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha) persisted when all the nonpregnant groups were examined at 6 months postpartum (P = 0.05) but now accounted for only 7% of the variance. Conclusion: In proteinuric preeclampsia, plasma endothelin 1 is independently negatively correlated with 2,3-dinor-6-keto-PGF(1 alpha) and plasma albumin. The negative relationship between these variables in preeclampsia may be due to a common underlying cause or a direct pathophysiological link. The relationship between plasma endothelin and urinary 2,3-dinor-6-keto-PGF(1 alpha) in the nonpregnant state suggests that there is normally a functional relationship between these two endothelial-derived factors, which may be due to direct inhibition of gene transcription by prostacyclin. Withdrawal of such inhibition may contribute to increased endothelin levels in preeclampsia.