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Effect of ethacrynic acid on the thick ascending limb of Henle's loop

1973; Elsevier BV; Volume: 4; Issue: 5 Linguagem: Francês

10.1038/ki.1973.121

1523-1755

Maurice B. Burg, Nordica Green,

Plant-based Medicinal Research

Effect of ethacrynic acid on the thick ascending limb of Henle's loop. Cortical thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro . The diuretic ethacrynic acid (10 -3 M) in the tubule lumen caused a reversible decrease in the electrical PD. Ethacrynic-cysteine complex, a major urinary excretion product of ethacrynic acid, also caused a reversible decrease in the PD as well as in net chloride transport, but at a much lower concentration (3 × 10 -6 M) in the lumen. Ethacrynic-cysteine in the bath (10 -5 M) had no effect on the PD. Ethacrynic-cysteine had little effect on Na and Cl conductances, measured electrically. On the basis of these results we suggest that the ethacrynic-cysteine complex is the major active form of the drug in vivo and that it acts in the lumen of the thick ascending limb of Henle's loop to inhibit active Cl transport and thereby diminish NaCl reabsorption. Effet de l'acide ethacrynique sur la partie large de la branche ascendante de l'anse de Henle. Des branches ascendantes larges corticales d'anses de Henle ont ete dissequees a partis de veins de lapins et perfusees in vitro . L'acide ethacrynique (10 -3 M) dans la lumiere tubulaire determine une inhibition reversible de la difference de potentiel electrique. Le complexe ethacrynique-cysteine, un produit d'excretion urinaire majeur de l'acide ethacrynique, determine aussi une diminution reversible de la difference de potentiel et du transport net de chlore, mais a une concentration luminale moindre (3 × 10 -6 M). Le complexe ethacrynique-cysteine dans le bain n'a pas d'effet sur la difference de potential. Le complexe a peu d'effets sur les conductances Na et Cl mesurees electriquement. Sur la base de ces resultats, nous suggerons que le complexe ethacrynique-cysteine est le forme active majeure de la drogue in vivo et qu'il agit dans la lumiere de la partie large de la branche ascendante de l'anse de Henle en inhibant le transport actif du chlore et, de ce fait, en diminuant la reabsorption du NaCl.