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Equol is a modest natriuretic and vasorelaxant agent in the rat. Further studies are required in order to investigate the potential natriuretic and perhaps hypotensive actions of dietary equol precursors (daidzein).

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Abstract-The urinary isoflavonoid genistein inhibits membrane Na-K-Cl cotransporters at similar concentrations as furosemide, but the significance of this action is unknown. Genistein was therefore investigated in rats for its potential salidiuretic actions. In the isolated, perfused rat kidney, genistein induced a maximal salidiuretic action similar to that of furosemide but was 3 to 5 times less potent than furosemide in terms of active doses (natriuresis EC 50 , 237Ϯ92 versus 56Ϯ20 mol/L for genistein and furosemide, respectively). Genistein and furosemide had no additive salidiuretic actions. Genistein had no significant effect on glomerular filtration rate but was able to significantly reduce renal vascular resistance with respect to vehicle isolated perfused kidney. Indomethacin (10 mol/L), a blocker of prostaglandin biosynthesis, reduced salidiuresis and renal vasorelaxation by genistein. Subcutaneous genistein (15 mg/kg) induced a statistically significant increase in diuresis and natriuresis with respect to vehicle during the first 6 hours of administration in rats. In conclusion, genistein compares well with furosemide in vitro for its salidiuretic profile and potency in the isolated perfused rat kidney and is also natriuretic by the subcutaneous route in the rat. Further studies are required to investigate potential natriuretic and perhaps hypotensive actions of dietary genistein.(Hypertension. 1998;31:706-711.)Key Words: genistein Ⅲ isoflavonoids Ⅲ kidney Ⅲ natriuresis Ⅲ rats R at urine contains compounds potently inhibiting furosemidesensitive Na-K-Cl cotransporters (cotransport inhibitory factors [CIF]). [1][2][3][4] Recently, one of such compounds was purified and structurally characterized as the isoflavonoid phytoestrogen equol (3,4-dihydro-3-(4-hydroxyphenyl)-2H-1-benzopyran-7-ol, see structure in Fig 1; see also Reference 2). Equol has similar potency as furosemide to inhibit cotransport, is a modest natriuretic agent in the rat, and can be excreted at urinary concentrations sufficient to partially inhibit cotransport at the luminal border of the thick ascending limb of Henle's loop (TALH). 2,5 Besides equol, two other isoflavonoids (genistein and daidzein, see structures in Fig 1) are biologically relevant and are present in mammalian urine. 6,7 Genistein but not daidzein was found here to be a potent cotransport inhibitor in the LLC-PK1 renal tubular cell line. Therefore genistein was further investigated for its salidiuretic properties in the isolated, perfused rat kidney (IPK) and in vivo by the subcutaneous route in the rat. Methods AnimalsGroups of 10 to 20 male Wistar rats (weight, 270 to 300 g; obtained from Interfauna, San Feliu de Codines, Spain) were kept for at least 1 week in our animal quarter before the study. The animals were housed in cages maintained in a humidity-and temperature-controlled room and fed a standard diet containing 34.2 mmol/kg NaCl. Tap water was given ad libitum. The investigation was performed according to the European Community guidelines for animal ethical...