Renal acification during chronic hypercapnia in the conscious dog

Abstract

Enhanced renal acidification during chronic hypercapnia (CH) results in transient augmentation in net acid excretion (NAE) (adaptation phase) and persistent acceleration in renal bicarbonate reclamation (adaptation and steady-state phases). The mechanisms responsible for the return of NAE to control values despite persistent acidemia during the steady state phase of CH remain undefined. In addition, it remains unsettled whether the enhancement of renal ammoniagenesis known to occur during the adaptation phase of CH persists during the steady-state phase. Furthermore it is uncertain if the alteration in whole-kidney acification observed in CH originates from augmentation in the acification of both proximal and distal nephronal segments.

To shed further light on these issues, observations on the profile of the urine acid-base moieties during the adaptive and steady-state phases of CH were carried out in dogs chronically exposed to hypercapnia (10% FiCO₂) in an environmental chamber (13 days). Additionally, collecting duct hydrogen ion secretion (CDH⁺S) was evaluated by employing the U-BPCO₂ in alkaline urine in intact unanesthetized dogs with either CH (10% FiCO₂) or eucapnia. The balance studies demonstrated that NAE increased in early hypercapnia (4.84 meq/kg body weight, control 3.27 meq/kg body weight,p<0.05) and returned to baseline thereafter; by contrast, urine NH ⁺₄ which was augmented during the adaptation phase (3.71 meq/kg body weight, control 1.97 meq/kg body weight,p<0.05) remained elevated throughout (3.25 meq/kg body weight). Moreover, steady-state chronic hypercapnia was accompanied by a decrease in urine titratable acidity (1.07 meq/kg body weight, control 1.46 meq/kg body weight,p<0.05) and an increase in urine bicarbonate (0.51 meq/kg body weight, control 0.16 meq/kg body weight,p<0.05) and pH (6.44, control 6.06,p<0.05). Evaluation of the U-BPCO₂ in alkaline urine in eucapnic and hypercapnic dogs revealed no significant differences between the two groups at comparable urine bicarbonate concentrations. Our data provide evidence that CH effects a persistent stimulation of renal ammoniagenesis but no augmentation in CDH⁺S. The return of NAE to baseline during the steady-state phase results from a decrease in titratable acidity and persistent bicarbonaturia that counterbalance the chronic enhancement in ammoniagenesis. The results suggest that the entire renal response to CH originates from proximal nephronal sites.