Regulation of Na/H exchange in renal microvillus vesicles in chronic hypercapnia

Abstract

Several disturbances of acid-base balance, including chronic metabolic and respiratory acidoses and metabolic alkalosis, are associated with enhanced proximal tubule bicarbonate reabsorption. To determine whether augmented brush border Na/H exchange might mediate enhanced proximal tubule bicarbonate reabsorption in these disorders, we measured Na/H exchange activity in cortical brush border membrane vesicles (BBMV) prepared from rats and rabbits adapted to hypercapnia and other chronic acid-base disturbances. BBMV prepared from control animals and animals with chronic acid-base disturbances were similar as judged by marker enzymes, alkaline phosphatase, and ouabain-sensitive phosphatase. Despite profound respiratory acidosis, no increase in Na/H exchange activity could be detected in vesicles prepared from rats adapted to chronic (8 to 10 days) or subacute (24 hr) respiratory acidosis. In addition, vesicles prepared from rabbits exposed to chronic hypercapnia did not show increased Na/H exchange when compared with contemporaneous controls. By contrast, in agreement with previously published results, amiloride-sensitive sodium uptake was increased by 30% in vesicles derived from animals with ammonium chloride-induced acidosis compared with contemporaneous controls. Two models of chronic metabolic alkalosis were also studied; vesicles from alkalotic rats did not show any alteration in Na/H exchange. We conclude that metabolic acidosis, but not respiratory acidosis or metabolic alkalosis, leads to enhanced activity of the luminal Na/H exchanger.