Effect of respiratory acidosis and respiratory alkalosis on renal transport enzymes

Abstract

We studied the effect of respiratory acidosis and respiratory alkalosis on acid-base composition and on microdissected renal adenosinetriphosphatase (ATPase) enzymes. Rats were subjected to hypercapnia or hypocapnia of 6, 24, and 72 h duration. After 6 h of hypercapnia, collecting tubule (CT) ATPases were not changed. At 24 h, plasma bicarbonate was 35 +/- 1 meq/l (P < 0.01) and CT H-ATPase and H-K-ATPase activities were 90% greater than controls (P < 0.01). By 72 h, plasma bicarbonate was 37 +/- 1 meq/l (P < 0.005 vs. control) and CT enzyme activity had increased even more, averaging approximately 130% of control (P < 0.05). Significant increases in enzyme activities were also observed in the proximal convoluted tubule and medullary thick ascending limb. Plasma aldosterone was three to four times that of control at all three time periods. In hormone-replete adrenalectomized rats, acid-base parameters and ATPase activities were the same as those seen in adrenal intact animals. After 6 h of hypocapnia, plasma bicarbonate was not significantly changed, but H-ATPase and Na-K-ATPase activities were decreased by 35% along the entire nephron (P < 0.05). H-K-ATPase activity in CT also decreased by 35%. At 24 h, plasma bicarbonate was 20.5 +/- 0.5 meq/l (P < 0.05 vs. control) and CT H-ATPase and H-K-ATPase activities were 60% less than control (P < 0.01). By 72 h, plasma bicarbonate was 18.5 +/- 0.5 meq/l (P < 0.05); however, only CT H-ATPase activity continued to fall, averaging 75% less than control (P < 0.005). Hypocapnia had no effect on plasma aldosterone or potassium. These results demonstrate that chronic, but not acute, respiratory acidosis stimulates activity of both renal proton ATPases. By contrast, both acute and chronic respiratory alkalosis decrease the two renal proton pumps. The stimulatory effect of hypercapnia and the inhibitory effect of hypocapnia on the renal ATPases appear to be potassium and aldosterone independent. Although the precise mechanisms for these results are not known, a direct effect of PCO2, pH, or changes in bicarbonate delivery may be involved.