Effects of furosemide,acetazolamide, and mannitol on medullary collecting-duct function in the rat kidney

The microcatheterization technique was used to study transport of fluid, sodium, and potassium in the medullary collecting duct in rats (232–357 g) before and during administration of diuretic drugs. Series I received furosemide (1.5 mg initial dose + 1.5 mg/h), Series II acetazolamide (0.75 mg +0.75 mg/h), and Series III and IV mannitol at 0.3 g+0.3 g/h, and 0.3 g+1.0 g/h, respectively. All diuretics caused diuresis, natriuresis, and kaliuresis. The renal response to furosemide and acetazolamide was associated with increased hematocrit and decreased filtration rate, indicating depletion of blood volume. No such effect was seen in Series III and IV. In the collecting duct furosemide completely abolished the normal reabsorption of sodium and fluid and initiated net secretion of potassium. Partial inhibition of salt and water transport in the collecting duct was observed with acetazolamide and the low dose of mannitol (III). Both treatments resulted in potassium secretion. In Series IV the high rate of mannitol infusion was associated with complete inhibition of salt and water reabsorption from the medullary collecting system similar to that of Series I. The greater excretory response in this group compared to the furosemide series was due to increased delivery of tubular load to the collecting duct. It is concluded that a major site of action of furosemide is in the medullary duct, resulting in quantitative inhibition of salt and water reabsorption from this nephron segment. The partial transport inhibition during acetazolamide or modest mannitol diuresis can be explained by the presence of poorly absorbable solute in duct fluid. The mechanism of inhibition of reabsorption after the high rate of mannitol infusion remains undetermined.