Effects of the diuretic torasemide on p-aminohippuric acid transport in the rat

Abstract

The effect of torasemide, a new diuretic, on p-aminohippuric acid (PAH) transport (TPAH) was studied using renal clearance and micropuncture techniques in anaesthetized rats. In clearance experiments, TPAH and TPAH/glomerular filtration rate (GFR) did not significantly change after i.v. administration of torasemide or furosemide but decreased after probenecid injection. In order to enhance the possibility to demonstrate torasemide and PAH interference, small volumes of [3H]-PAH + [14C]-inulin solutions were directly injected into the peritubular capillary system using calibrated micropipettes. When the concentration of microinjected PAH was less than or equal to 0.6 mmol/l, fractional recovery of [3H]-PAH from the micropunctured kidney was not significantly decreased by the diuretics in contrast to probenecid. When the concentration of microinjected PAH was greater than or equal to 5 mmol/l, fractional recovery of [3H]-PAH from the micropunctured kidney was significantly decreased by torasemide from 252% (control) to 210% (P less than 0.005), by furosemide to 217% (P less than 0.005), and by probenecid to 205% (P less than 0.01). Under these conditions, differential transit times between [3H]-PAH and [14C]-inulin in the micropunctured kidney were decreased from -15 to -4 s in the presence of torasemide (P less than 0.05). They were slightly but not significantly reduced by furosemide and probenecid. These findings suggest interference, at least to some extent, between torasemide and PAH secretion in the rat kidney.