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The separate modes and sites of action of furosemide and amiloride.

The effect of furosemide and amiloride on the transport of sodium, potassium, hydrogen and bicarbonate ions was studied in microperfusion experiments on the main excretory duct of the submaxillary gland of the rat. Furosemide did not impair transport of Na+, K+ and H+/HCO-3. Amiloride, however, completely abolished Na+ transport. Blockade of Na+ transport was accompanied by abolition of passive K+ secretion, whereas the active components of K+ and HCO-3 secretion were not affected. In urinary excretion studies, amiloride, which is known to block sodium transport selectively, was used in order to assess whether furosemide has a distinct effect that is independent of sodium transport. Oral administration of amiloride caused a selective excretion of Na+ in a more alkaline urine with an extremely low K+ concentration. The injection of furosemide caused a copious diuresis of an isotonic urine, in which excretion of Na+ and K+ was balanced by the excretion of Cl- ions. Combined administration of amiloride and furosemide produced summation of the individual effects of both diuretics, indicating that the two drugs had different sites and modes of action. In the presence of furosemide the kidney no longer responded to antidiuretic hormone, which suggested that the urine concentrating mechanism in Henle's loop was blocked by furosemide.