DIMINISHED DIURETIC AND NATRIURETIC RESPONSE TO FUROSEMIDE IN POTASSIUM-DEPLETED RATS

Renal clearance and tubule microperfusion experiments were carried out to investigate the effects of chronic potassium depletion upon the re nal response to furosemide. Rats kept on a potassium-deficient diet fo r 3 weeks developed hypokalemia, metabolic alkalosis, and decreased al dosterone levels. These rats responded to an oral administration of fu rosemide (32 mg/kg) with a blunted excretion rate of urine and sodium. Whereas furosemide increased fractional urine sodium excretion to 5.2 % in control rats, the corresponding rate in potassium-depleted rats w as 2.8%. The urinary excretion of furosemide was also significantly re duced during potassium depletion from 3.06 mg/kg in control rats to 0. 97 mg/kg in potassium-depleted rats. In separate experiments, loops of Henle were pump-perfused with furosemide-containing solutions in cont rol and potassium-depleted rats. No major modification of the inhibito ry effects of furosemide on sodium transport was observed when the pot assium concentration of the perfusion fluid was kept at the low levels expected in hypokalemic rats. Metabolic alkalosis unaccompanied by po tassium deprivation did not decrease the diuretic response to furosemi de. These experiments indicate that potassium deprivation reduces the diuretic effects of furosemide by mechanisms including diminished furo semide delivery to its tubule site of action.