Evidence against a pathogenetic role for endothelin in pre‐eclampsia

Abstract

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 bigendothelin‐1 and endothelin‐1, 2 and 3, were comparable in placental tissue from pre‐eclamptic and normal pregnant women. Plasma levels of endothelin‐1 did not differ between pre‐eclamptic 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 decreased 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.