Proximal tubule response in aldosterone escape

The response of the proximal tubule to chronic aldosterone administration (15 micrograms.kg-1.day-1) was evaluated in eight conscious female mongrel dogs. Temporal profiles between hemodynamic and hormonal changes and the fractional excretions of sodium and lithium were established. Aldosterone infusion resulted in a significant decrease in urinary sodium excretion from 9.2 +/- 1.3 to 5.8 +/- 0.9 meq/h after 1 day, returning to normal by the 5th day. These changes in urinary sodium excretion were associated with significant elevations of the mean arterial pressure (MAP) from 105 +/- 5 to 111 +/- 6 mmHg and plasma atrial natriuretic factor concentrations (ANF) from 30 +/- 2 to 57 +/- 7 pg/ml beginning the 1st day of infusion. Plasma renin activity (PRA), on the other hand, was depressed by aldosterone, falling below the level of detectability. The fractional excretion of lithium increased significantly by day 2 of aldosterone infusion (from 29 +/- 3 to 44 +/- 6%), reflecting the proximal tubular response to the above changes. We conclude that the proximal tubule responds to increases in MAP and ANF and decreases in PRA during aldosterone infusion by decreasing sodium reabsorption. Subsequent nephron segments must also respond to the volume expansion produced by aldosterone, since the sustained proximal tubule natriuretic response is insufficient to explain all of escape.