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 (JHCO3) 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 (FEHCO3) increased threefold, but LOH JHCO3 was unchanged. In ARA, blood pH fell to 7.2, and blood [HCO3-] rose from 28 to 34 mM; FEHCO3 was reduced to < 0.1%, but LOH JHCO3 was unaltered. In CRA, blood pH fell to 7.2, and blood [HCO3-] increased to > 50 mM, whereas FEHCO3 decreased to < 0.1%. JHCO3 was reduced by approximately 30%. Bicarbonaturia occurred when CRA rats breathed air, yet LOH JHCO3 increased (by 30%) to normal. These results suggest that LOH JHCO3 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 JHCO3 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 JHCO3) was used, JHCO3 was -112.8 +/- 5.6 pmol/min. Comparable values for JHCO3 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 JHCO3 in vivo.