Renal endothelin-1 is linked to changes in urinary salt and volume in essential hypertension

Methods: We investigated the influence of salt intake on urinary and plasma endothelin-1 (ET-1) in 55 patients who entered a two-week double-blind, randomised, crossover study comparing a 50 mMol/day salt intake and 150 mMol/day. Twenty-four-hour ET-1 excretion and plasma ET-1 were measured by RIA on pre-extracted samples. Results: In the whole cohort (n=55), changes in urinary ET-1 were related to salt excretion (r=0.28, P=0.04) and urinary volume (r=0.47, P=0.0001). In a multivariable model, changes in PRA, plasma aldosterone, blood pressure and heart rate did not add any predictive power to salt excretion with regard to urinary ET-1 variations. The relationship between urinary volume and urinary ET-1 was stronger than that of urinary sodium with ET-1 excretion because sodium was excluded from the multivariable model when urinary volume was introduced. Changes in urinary ET-1 were unrelated to mean blood pressure changes (P=0.66). Changes in plasma ET-1 were unaffected by changes in salt intake (P=0.58) but were strongly related to those in PRA (r=-0.45, P=0.01) and plasma aldosterone (r=-0.53, P=0.002). Conclusions: The renal excretion of ET-1 is influenced by changes in salt intake and appears largely independent of the blood pressure response to salt. Changes in urinary volume which accompany variations in salt excretion play an important role in this response. Since urinary ET-1 reflects its renal synthesis, our data support the notion that renal ET-1 plays a role in the regulation of sodium balance in patients with mild hypertension.