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

Abstract

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