Proximal tubular acidification in metabolic alkalosis

Metabolic alkalosis was induced in rats by acute bicarbonate loading in the presence and absence of extracellular volume (ECV) expansion. Proximal tubular acidification was studied by stopped-flow microperfusion and the determination of luminal pH by antimony microelectrodes. Stationary pH and bicarbonate were markedly increased in proximal tubules of alkalotic rats, and acidification half-times were increased, leading to a fall in net bicarbonate reabsorption (JHCO-3) to 36% of control values. Net H+ ion secretion (JH+) into phosphate buffer fell to 56% of controls, whereas alkalinization t/2 and H+ fluxes, measured during perfusion with acid phosphate, were unaltered. ECV expansion reduced proximal JHCO-3 36% in control rats, without affecting JH+, and caused a fall in alkalinization t/2, compatible with increased bicarbonate back-flux into the lumen. However, it did not affect JHCO3 and JH+ in alkalotic rats. Carbonic anhydrase inhibition did not significantly reduce acidification in alkalotic rats. An analysis of the components of bicarbonate reabsorption showed that alkalosis reduced catalyzed H+ -ion secretion to 7% of the control values. It is concluded that proximal H+ ion secretion is significantly reduced in metabolic alkalosis leading to lower JHCO-3. No evidence for modification of H+/HCO-3 apparent permeabilities was obtained. The effects of alkalosis were not significantly altered by ECV expansion or by carbonic anhydrase inhibition.