Dose-related effects of furosemide, bumetanide, and piretanide on the thick ascending limb function in the rat

To assess the action of piretanide, bumetanide, and furosemide on the thick ascending limb of Henle's loop, perfusion experiments were performed on rat kidneys, using a recently developed conductivity microprobe for the analysis of distal tubular fluid. Surface nephrons were perfused downstream from a solid paraffin block through Henle's loop with isotonic saline solution containing either 10(-6), 3 X 10(-6), or 10(-5) mol/L piretanide, bumetanide, or furosemide, respectively. For control values, diuretic-free saline was used. Conductivity measurements of early distal tubular fluid were performed in situ with a conductivity microprobe and were recorded continuously during variations of loop perfusion rate. A recently described micro-stop-flow technique was used to measure the conductivity of fluid emerging from the ascending limb, thereby evaluating the amount of sodium chloride reabsorbed. A significant electrolyte transport inhibition occurred within the concentration range between 10(-6) and 10(-4) M. Bumetanide and piretanide were slightly more effective than furosemide. Luminal diuretic concentrations of 10(-6) M or below were without influence on electrolyte reabsorption. Concentrations of 10(-4) M resulted in complete inhibition of the diluting segment electrolyte transfer.