Abstract

Hydrochlorothiazide (HCTZ)-induced Na requirement was examined in rats fed a standard diet containing 250 mg of HCTZ per kg of food and given a free choice between water and 0.46 M NaCl. HCTZ treatment led to a persistent 8-fold increase of NaCl intake. An increase of the K content of the food from 100 to 600 mmol/kg reduce the NaCl intake by 75%. Maintenance on a high K diet prevented the HCTZ-induced requirement for extra Na and diminished HCTZ-induced loss of body weight and urinary loss of Na. Determinations of lithium clearance (CLi) in unanesthetized rats by using nontoxic doses of lithium was used as a measure of Na clearance at the end of the proximal tubules (CNa prox). The urinary sodium clearance divided by the urinary lithium clearance (CNa/CLi) was used to express the fractional escape of Na from distal reabsorption. In HCTZ-treated rats, maintenance on a high K diet reduced CNa and CNa/CLi. A high potassium intake increased CNa prox, but this effect was least in HCTZ-treated rats. The results show that a high K intake reduced the natriuretic effect of HCTZ. The renal mechanism is presumably a potassium-induced compensatory increase of the reabsorption of Na delivered from the proximal tubules.