Translational Physiology Fractional urinary excretion of endothelin-1 is reduced by acute ETB receptor blockade

Goddard J, Johnston NR, Cumming AD, Webb DJ. Fractional urinary excretion of endothelin-1 is reduced by acute ETB receptor blockade. Am J Physiol Renal Physiol 293: F1433–F1438, 2007. First published September 12, 2007; doi:10.1152/ajprenal.00101.2007.— Evidence suggests that urinary excretion of endothelin-1 (ET-1) reflects renal ET-1 production and is independent of systemic ET-1 activity. The influence of ET receptors on urinary ET-1 excretion has not been studied in humans, yet peritubular ETB receptors are abundant within the kidney. We have studied the effects of acute ETA and ETB receptor blockade with BQ-123 and BQ-788, respectively, on urinary ET-1 excretion in a randomized, placebo-controlled, doubleblind study in 16 subjects with a wide range of GFRs (15–152 ml/min). Plasma ET-1 concentrations (pET-1) and urinary ET-1 excretion rate (uET-1) at baseline correlated inversely with GFR (R 0.18 and 0.36, respectively, P 0.01). However, changes in pET-1 after ET receptor antagonism were not related to changes in uET-1 (R 0.007, P 0.18). pET-1 increased only after BQ-788, alone or in combination with BQ-123, consistent with ETB receptormediated clearance of ET-1 from the circulation. uET-1 was reduced only after BQ-788 alone [ 4.7 pg/min (SD 5.5), P 0.01]. Because BQ-788 also reduced GFR, fractional excretion of ET-1 (FeET-1) was calculated. FeET-1 fell after BQ-788 alone [ 41% (SD 26%), P 0.01] or in combination with BQ-123 [ 40% (SD 29%), P 0.01]. FeET-1 was not altered by placebo or BQ-123 alone. In conclusion, urinary ET-1 excretion does not appear to relate to the pool of plasma ET-1. Because of the short duration of this study, it is unlikely that ET receptor blockade had significant effects on renal ET-1 production. Therefore, the reduction in FeET-1 after ETB blockade appears to indicate that renal excretion of ET-1 is at least partly facilitated by ETB receptor activation.