The effect of chronic hyperfiltration, a model of cell hypertrophy, on H/HCO3 transporters was examined in the in vivo microperfused rat proximal tubule. Hyperfiltration was induced by uninephrectomy with subsequent increased dietary protein. After 2 wk the hyperfiltration group had a higher glomerular filtration rate (2.21 +/- 0.13 vs. 1.48 +/- 0.12 ml/min), associated with increased kidney weight (1.71 +/- 0.05 vs. 1.23 +/- 0.04 g). HCO3 absorptive rate measured in tubules perfused with an ultrafiltrate-like solution (25 mM HCO3) was higher in the hyperfiltration group (183 +/- 17 vs. 109 +/- 16 pmol/mm per min). The activities of the apical membrane Na/H antiporter and basolateral membrane Na/3HCO3 symporter were assayed using the measurement of cell pH [(2'7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein] in the doubly microperfused tubule in the absence of contact with native fluids. After 2 wk of hyperfiltration Na/H antiporter activity, assayed as the effect of luminal Na removal on cell pH, was increased 114%. Basolateral membrane Na/3HCO3 symporter activity, assayed as the effect of a decrease in peritubular [HCO3] (25 to 5 mM) or in peritubular [Na] (147 to 25 mM) in the absence of luminal and peritubular chloride, was increased 77 and 113%, respectively, in the hyperfiltration group. Steady-state cell pH, measured with physiologic, ultrafiltrate-like luminal and peritubular perfusates, was significantly higher in the hyperfiltration group (7.27 +/- 0.02 vs. 7.14 +/- 0.03). In similar studies, performed 24 h after uninephrectomy and protein feeding, kidney weight was increased 10%, Na/H antiporter activity 39%, and Na/3HCO3 symporter activity 46%. At this time cell pH was not different between the two groups. The results demonstrate that chronic hyperfiltration is associated with parallel increases in Na/H antiporter and Na/3HCO3 symporter activities. If a decrease in cell pH is the signal that triggers these adaptations, it occurs early, and the adaptations can be maintained in the absence of sustained cell acidification.

This content is only available as a PDF.