In
puromycin aminonucleoside (PAN)-treated nephrotic rats,
sodium retention is associated with increased (Na+/K+)-
ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-
ATPase in the CCD is a feature of other experimental
nephrotic syndromes, whether it might be responsible for renal
sodium retention, and whether it is mediated by increased plasma
vasopressin levels or activation of
calcineurin. For this purpose, the time courses of urinary excretion of
sodium and
protein,
sodium balance,
ascites, and (Na+/K+)-
ATPase activities in microdissected CCD were studied in rats with PAN or
adriamycin nephrosis or
HgCl2 nephropathy. The roles of
vasopressin and
calcineurin in PAN
nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with
cyclosporin or
tacrolimus. Despite different patterns of changes in urinary
sodium and
protein excretion in the three
nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-
ATPase activities and
sodium excretion in all three cases. The results also indicated that there was no correlation between
proteinuria and
sodium retention, but
ascites was present only when
proteinuria was associated with marked reduction of
sodium excretion. Finally, the lack of
vasopressin in Brattleboro rats or the inhibition of
calcineurin by administration of either
cyclosporin or
tacrolimus did not prevent development of the
nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-
ATPase. It is concluded that stimulation of Na(+/K+)-
ATPase in the CCD of nephrotic rats might be responsible for
sodium retention and that this phenomenon is independent of
proteinuria and
vasopressin and
calcineurin activities.