Determinants of proximal bicarbonate, chloride, and water reabsorption during carbonic anhydrase inhibition

To examine the magnitude and load dependency of proximal reabsorption during carbonic anhydrase inhibition with acetazolamide, Munich-Wistar rats were studied in hydropenia and following an increase in single nephron glomerular filtration rate (SNGFR) by either plasma or colloid-free Ringer expansion. During acetazolamide administration, when plasma loading increased SNGFR 50% compared with hydropenia, total CO2, chloride, and water proximal reabsorption rose proportionally, so that fractional proximal reabsorption rates remained constant (0.20-0.27). When SNGFR was comparably increased with Ringer expansion, total CO2, chloride, and water reabsorption were decreased relative to their respective rates during plasma expansion and, in fact, were not changed compared with hydropenic values. At all flow rates during carbonic anhydrase inhibition, end-proximal total CO2 and chloride concentrations were only slightly higher than in the glomerular ultrafiltrate, so that reabsorption was isohydric. In further studies, proximal reabsorption remained isohydric when the glomerular ultrafiltrate bicarbonate concentration was reduced in metabolic acidosis. In conclusion, absolute proximal reabsorption of bicarbonate, chloride, and water during carbonic anhydrase inhibition 1) proceeds isohydrically, with minimal anion concentration gradients generated, over a wide range of filtered loads, and 2) can be flow dependent (with plasma loading) as well as modulated by peritubular protein concentration, even though passive chloride transport is minimized.