Abstract
A potent inhibitor of the Na-K-Cl cotransport system was purified from urines of salt-loaded rats. Mass spectroscopy revealed a molecular mass of 242 Da. Nuclear magnetic resonance showed a spectrum identical to that of 3,4-dihydro-3-(4-hydroxyphenyl)-2H-1-benzopyran-7-ol (an “estrogen-like” isoflavonoid: equol). This compound inhibited cotransport fluxes at similar concentrations (IC50= 16–24 μM) as furosemide (IC50≈ 10μM). Cotransport inhibitory activity of urines from rats drinking tap water was fully explained by urinary equol concentrations (≈ 27 μM, measured by high-performance liquid chromatography). Salt-loading increased urinary equol excretion, but not sufficiently high to fully explain the very important increase in cotransport inhibitory potency. We conclude that: (i) under basal conditions urinary equol can regulate Na-K-Cl cotransport activity in the kidney and (ii) salt-loading should evoke the appearance of other cotransport inhibitors.
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