Inhibition of active NaCl reabsorption in the thick ascending limb of the loop of Henle by torasemide.

The new diuretic torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) was tested in isolated in vitro perfused cortical thick ascending limbs of Henle loops of rabbit kidney. The equivalent short circuit current (Isc) corresponding in this nephron segment to the rate of secondarily active Cl-reabsorption was measured continuously. Torasemide led to a rapid and reversible inhibition of Isc when added to the luminal perfusate. The IC50 for this effect was 3 x 10(-7) mol/l. A similar effect was also exerted by torasemide addition to the peritubular bath. However, 100 times larger doses were needed. The data are compatible with the view that torasemide interacts with both, the Na+2Cl-K+ carrier, localized in the luminal membrane, and, at higher concentrations, with the chloride channels present in the basolateral membrane of this nephron segment. Under normal conditions, and in the intact kidney, the former effect, i.e. interference with the Na+2Cl-K+ carrier will be the dominant action of this drug.