Frusemide pretreatment blunts the inhibition of renal tubular sodium reabsorption by ANF in man.

The effects of atrial natriuretic factor (ANF) 15 pmol/kg/min on renal function were studied in 7 normal male volunteers during maximal water diuresis. Subjects were studied in neutral salt balance either before, or after, seven days treatment with 40 mg oral frusemide. The post-frusemide state was associated with activation of the renin-angiotensin system (RAAS) and generally higher noradrenaline levels; this state was also associated with sodium retention, mainly due to enhanced distal nephron reabsorption. Without diuretic pretreatment ANF produced a natriuresis and diuresis associated with inhibition of both proximal and distal nephron sodium reabsorption. In contrast, after frusemide pretreatment, ANF caused an increase in water excretion (urinary flow rate) but no change in sodium excretion. In the post-diuretic condition ANF did not affect renal tubular handling of sodium. The enhanced tubular reabsorption of sodium post-frusemide, and the failure of ANF to suppress this, could be due to activation of the RAAS and SNS.