Tubular site of the natriuresis after unilateral nephrectomy in the rat

Unilateral nephrectomy (UNX) is followed by a prompt increase in sodium excretion from the remaining kidney. Recently, an important role for atrial natriuretic peptide (ANP) in mediating the UNX-associated natriuresis has been suggested. The present studies were undertaken to gain insight into the intrarenal mechanisms participating in the post-UNX natriuresis in circumstances in which the release or the action of endogenous ANP were suppressed by prior removal of the right atrial appendage and by administration of monoclonal anti-ANP antibodies, respectively. In anesthetized euvolemic untreated rats, UNX resulted in a twofold increase in urinary excretion of sodium (from 0.93 +/- 0.23 to 2.14 +/- 0.34 microE/min; p < 0.03), whereas glomerular filtration rate did not change significantly. Fractional excretion of lithium, an index of proximal tubular handling of sodium, increased from 30.7 +/- 3.4% to 39.4 +/- 4.0%, and fractional distal reabsorption of sodium decreased from 98.6 +/- 0.2% to 96.5% +/- 0.4% (both p < 0.006). Neither sham atrial appendectomy nor the administration of nonspecific antibodies affect the natriuretic response of the remaining kidney. The natriuretic response to UNX was abolished in right atrial appendectomized rats, as well as in rats receiving anti-ANP antibodies. Post-UNX changes in both proximal and distal tubular reabsorption of sodium were also suppressed in these animals. These observations indicate that ANP may be an important mediator of the natriuretic response to UNX and that the proximal and the distal part of the nephron contribute to the postnephrectomy natriuresis.