Effect of acute hypercapnia on renal and proximal tubular total carbon dioxide reabsorption in the acetazolamide-treated rat

The present study evaluates the effect of acute hypercapnia on renal total CO₂ (tCO₂) reabsorption after inhibition of renal carbonic anhydrase. Simultaneous renal clearance studies and free-flow micropuncture studies of the superficial proximal tubule were performed on plasma-repleted Sprague-Dawley rats treated with acetazolamide, 50 mg/kg body weight. Acute hypercapnia (arterial P(CO₂), 120 mmHg; blood pH, 7.02) was induced by ventilation with a 10% CO₂-90% O₂ gas mixture. Control rats (P(CO₂), 49.5 mmHg, pH 7.34) were ventilated with room air. The renal fractional excretion of tCO₂ was ~20% lower in the hypercapnic group compared with the rats given acetazolamide alone. Acute hypercapnia reduced the fractional delivery of tCO₂ to the late proximal tubule by a comparable amount. The absolute proximal reabsorption tCO₂ was increased by hypercapnia to 410 ± 47 vs. 170 ± 74 pmol.min^-1, P < 0.05. The single nephron glomerular filtration rate was 32.6 ± 0.7 nl.min^-1 in the hypercapnic group and 43.8 ± 1.7 nl.min^-1 in the rats given acetazolamide only, P < 0.01. Acute hypercapnia enhances renal sympathetic nerve activity. To eliminate this effect, additional experiments were performed in which the experimental kidney was denervated before study. Denervation prevented the change in the single nephron filtration rate during acute hypercapnia, but absolute and fractional proximal tCO₂ reabsorption remained elevated in comparison to denervated controls. The concentration of H₂CO₃ in the late proximal tubule, calculated from the measured luminal pH and bicarbonate concentration and the estimated cortical P(CO₂), was higher in the hypercapnic group, which was a finding compatible with H₂CO₃ cycling from lumen into proximal tubular cell, which provided a source of hydrogen ions for secretion.