We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block Na+ transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (30 mg/kg) Na+ and K+ excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved -subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriuresis that coincided with decreased pT53NCC and increased cleaved ENaC. Alterations in post-translational membrane protein processing correlated with an increase in plasma K+ of 0.6 to 0.8 mM. Decreased pT53NCC occurred within one hour after amiloride injection, while changes in ENaC were slower and were blocked by the mineralocorticoid receptor antagonist spironolactone. Increased ENaC cleavage correlated with elevation of the surface expression of the subunit as assessed by in situ biotinylation. Na depletion induced by 2 hours of furosemide or HCTZ treatment increases total NCC expression without affecting ENaC protein. However restriction of Na intake for 10 hours (during the day) or 18 hours (overnight) increased the abundance of both total NCC and of cleaved α and ENaC. We conclude that the kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC. They respond to hypovolemia more slowly, increasing Na+ reabsorptive capacities of both of these transporters.