Urinary pCO₂ as an index of collecting duct hydrogen ion secretion during chronic hypercapnia

The rise in urinary pCO₂ above blood pCO₂ which occurs in response to bicarbonate loading (i.e. the urine to blood (U-B) pCO₂ gradient), is used with increasing frequency as an index of collecting duct hydrogen ion secretion. We recently proposed, however, that the U-B pCO₂ gradient is not an appropriate index of collecting duct hydrogen ion secretion when blood pCO₂ is altered acutely. This issue was further investigated by examining the effect of chronic hypercapnia on urinary pCO₂ generation. In rats exposed to chronic hypercapnia induced by breathing 10% CO₂ for 3 days in an environmental chamber, acute sodium bicarbonate infusion resulted in a U-B pCO₂ lower than that of normocapnic control rats (11±4.6 and 30±1.8 mm Hg, p<0.001). This finding could be interpreted to indicate that collecting duct hydrogen ion secretion is depressed in rats with chronic hypercapnia. The urinary pCO₂ of rats with chronic hypercapnia was lower than that of the blood (54±6.0 and 86±1.2 mm Hg, p<0.005), respectively). In these rats, NaHCO₃ infusion, while blood pCO₂ was kept constant, elicited a marked rise in urine pCO₂ (from 54±6.0 to 104±6.0 mm Hg, p<0.005) which was not significantly different from that observed in normocapnic control rats. The infusion of carbonic anhydrase resulted in a comparable fall in urine pCO₂ in hypercapnic and normocapnic rats (-27±5 and -30±3 mm Hg). In rats with chronic hypercapnia treated with amiloride to inhibit collecting duct H⁺ secretion, the infusion of NaHCO₃ also resulted in a rise in urine pCO₂ (from 64±5.6 to 90±4.0 mm Hg, p<0.001). This increment in urine pCO₂ (i.e. the ΔpCO₂) was lower than that observed in rats with chronic hypercapnia not treated with amiloride (26±5.0 and 50±11 mm Hg, p<0.05) thereby demonstrating that maximal urinary pCO₂ generation in rats with chronic hypercapnia requires intact collecting duct H⁺ secretion. We conclude that in rats with chronic hypercapnia the U-B pCO₂ achieved during bicarbonate loading is subnormal owing to the high blood pCO₂, and not the result of impaired collecting duct hydrogen ion secretion. The normal rise in urinary pCO₂ elicited by sodium bicarbonate loading and the normal fall in urine pCO₂ after carbonic anhydrase infusion reflect that collecting duct H⁺ secretion in rats exposed to chronic hypercapnia is intact. In contrast, colleting duct H⁺ secretion is clearly underestimated by the U-B pCO₂ gradient.