Evidence against a pathogenetic role for endothelin in pre-eclampsia

Objective: To assess whether increased placental or systemic endothelin synthesis has a pathogenic role in pre-eclampsia (gestational proteinuric hypertension). Design: Prospective observations study. Subjects: 19 women with pre-eclampsia and 10 healthy pregnant women were studied. All were in the last trimester. Main outcome measures: Preproendothelin-1 gene expression by Northern blot analysis and generation of endothelin-1 precursor, big-endothelin-1, and endothelin isoforms, namely endothelin-1, 2 and 3, were assessed by specific radioimmunoassays, in placental tissue. Plasma endothelin-1 levels and urinary excretion of big-endothelin-1 and endothelin-1 were measured. Results: Placental preproendothelin-1 gene expression and immunoreactive big-endothelin-1 and endothelin-1, 2 and 3, were comparable in placental tissue from pre-eclampsia and normal pregnant women. Plasma levels of endothelin-1 did not differ between pre-eclampsia and normal pregnancies. In contrast, urinary excretion of endothelin-1, which is likely to reflect the renal synthesis of the peptide, was significantly decreased in pre-eclamptic, as compared with normal pregnant women. This was not due to a decreasd renal generation of endothelin-1 precursor, since urinary excretion of big-endothelin-1 did not differ between pre-eclamptic and normal pregnancies. These data suggest an increased renal endothelin-1 breakdown in pre-eclampsia. Conclusions: Endothelin is unlikely to play a role in the pathogenesis of pre-eclampsia. Instead, an increased renal breakdown may have a role in limiting the negative effects of other vasoactive factors on the renal circulation.