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Antidiuretic effects of endothelin B receptor antagonism
Author(s) -
Iliescu Radu,
Baltatu Ovidiu Constantin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.182
Subject(s) - diuretic , diuresis , endocrinology , medicine , chemistry , antidiuretic , renal function , endothelin receptor , natriuresis , free water clearance , kidney , renal blood flow , vasopressin , receptor
Activation of endothelin (ET)‐B receptors has diuretic and natriuretic effects. Whether these effects are mediated by renal hemodynamic mechanisms or by renal tubular inhibition of salt and water reabsorbtion is unclear. We tested the hypothesis that systemic administration of ET‐B receptor antagonist (BQ‐788) at concentrations devoid of renal hemodynamic effects leads to acute sodium and water retention. BQ‐788 (3mg/kg, i.v. bolus) or vehicle were administered to anesthetized rats (SD, n=5) undergoing saline diuresis (15 mL/kg/h, 1% BSA). Urine was collected from the bladder for 20 min while blood pressure (BP) and glomerular filtration rate (GFR) were monitored. BQ‐788 decreased urine output (115.4 ± 15 vs 150.1 ± 21 ìL/min, p<0.05) and fractional excretion of water (5 ± 0.3 vs 7.7 ± 1%, p<0.05) while urinary excretion rates and plasma concentrations of Na+ and K+ were not altered, as compared to vehicle. BQ‐788 increased BP by 6 ± 1 mmHg, but did not affect GFR (2.2 ± 0.1 vs 1.9 ± 0.1 mL/min, p=0.2). These data suggest that blockade of ET‐B receptors at concentrations that do not affect glomerular vascular tone leads to acute (20 min) and selective antidiuresis, without an apparent effect on renal sodium handling. This indicates that endogenous endothelin‐1 has a tonic diuretic effect mediated via renal ET‐B receptors and may explain why fluid retention occurs during treatment with non‐selective ET receptor blockers.