The effects of respiratory alkalosis and acidosis on net bicarbonate flux along the rat loop of Henle in vivo

We have studied the effects of acute respiratory alkalosis (ARALK, hyperventilation) and acidosis (ARA, 8% CO2), chronic respiratory acidosis (CRA; 10% CO2 for 7-10 days), and subsequent recovery from CRA breathing air on loop of Henle (LOH) net bicarbonate flux (J(HCO3)) by in vivo tubule microperfusion in anesthetized rats. In ARALK blood, pH increased to 7.6, and blood bicarbonate concentration ([HCO3 ]) decreased from 29 to 22 mM. Fractional urinary bicarbonate excretion (FE(HCO3)) increased threefold, but LOH J(HCO3) was unchanged. In ARA, blood pH fell to 7.2, and blood [HCO3] rose from 28 to 34 mM; FE(HCO3) was reduced to <0.1%, but LOH J(HCO3) was unaltered. In CRA, blood pH fell to 7.2, and blood [HCO3/-] increased to >50 mM, whereas FE(HCO3) decreased to <0.1%. J(HCO3) was reduced by ~30%. Bicarbonaturia occurred when CRA rats breathed air, yet LOH J(HCO3) increased (by 30%) to normal. These results suggest that LOH J(HCO3) is affected by the blood-to-tubule lumen [HCO3/-] gradient and HCO3/- backflux. When the usual perfusing solution at 20 nl/min was made HCO3 free, mean J(HCO3) was -34.5 ± 4.4 pmol/min compared with 210 ± 28.1 pmol/min plus HCO3. When a low-NaCl perfusate (to minimize net fluid absorption) containing mannitol and acetazolamide (2 x 10-4 M, to abolish H+-dependent J(HCO3)) was used, J(HCO3) was -112.8 ± 5.6 pmol/min. Comparable values for J(HCO3) at 10 nl/min were -35.9 ± 5.8 and -72.5 ± 8.8 pmol/min, respectively. These data indicate significant backflux of HCO3 along the LOH, which depends on the blood-to-lumen [HCO3] gradient; in addition to any underlying changes in active acid-base transport mechanisms, HCO3/- permeability and backflux are important determinants of LOH J(HCO3) in vivo.