RELATIONSHIPS BETWEEN PLASMA ENDOTHELIN AND PROSTACYCLIN IN NORMAL AND PREECLAMPTIC PREGNANCY

Objective: This study aimed to examine the relationships between plasm a endothelial 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha) and other bi ochemical variables in normal pregnancy, preeclampsia, and the nonpreg nant state using multiple regression analysis. Methods: Plasma endothe lin 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha) were measured after ex traction by specific radioimmunoassays in 20 women with proteinuric pr eeclampsia 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 w as 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 dependen t variable, a significantly negative correlation was found with urinar y 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 s ame model in the normal pregnant group showed only plasma albumin to b e significantly negatively correlated with plasma endothelin, and the model accounted for only 13% of the variance in plasma endothelin. Usi ng urinary 2,3-dinor-6-keto-PGF(1 alpha) as the dependent variable, an independent negative association was found with plasma endothelin 1 a nd a positive association with creatinine clearance in the preeclampti c group, accounting for 42% of the variance in urinary 2,3-dinor-6-ket o-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 nega tive association was again seen between plasma endothelin 1 and urinar y 2,3-dinor-6-keto-PGF(1 alpha). The inverse relationship between plas ma endothelin 1 and urinary 2,3-dinor-6-keto-PGF(1 alpha) persisted wh en 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 negativ ely 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 lin k. The relationship between plasma endothelin and urinary 2,3-dinor-6- keto-PGF(1 alpha) in the nonpregnant state suggests that there is norm ally a functional relationship between these two endothelial-derived f actors, which may be due to direct inhibition of gene transcription by prostacyclin. Withdrawal of such inhibition may contribute to increas ed endothelin levels in preeclampsia.