Changes in renal metabolite profile and ammoniagenesis during acute and chronic metabolic acidosis in dog and rat.
Acute metabolic acidosis was induced by an i.v. administration of hydrochloric acid to dogs and rats to decrease the plasma bicarbonate concentration from 22 to 12 mM in dogs and from 26 to 10 mM in rats. Chronic metabolic acidosis was also induced in dogs by ammonium chloride feeding for 5 days. Rats also were given ammonium chloride for 24 hours. The renal metabolite profile was determined on the freeze-clamped renal tissue before and after 100 min (dogs) or 30 to 240 min (rats) of acsute acidosis. Measurements on chronically acidotic dogs and rats with 24-hour acidosis were obtained also for comparison with acute acidosis. In both species, kidney glutamine, glutamate, and alpha-ketokglutarate concentrations decreased drastically following induction of acute or chronic acidosis, In the dog, or in the rat during the first 2 hours of acidosis, malate concentration was unchanged. Malate concentration fell significantly in the rat kidney only after 2 hours of acidosis without change in phosphoenolpyruvate (PEP) concentration. In chronically acidotic dogs, malate and oxaloacetate rose fivefold with no change in PEP concentration. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not stimulated by chronic metabolic acidosis in the dog in contrast to the rat. Acute acidosis by hydrochloric acid increased net renal glutamine extraction in the rat but not in the dog. These data suggest that an increased metabolic flux occurs between alpha-ketoglutarate and malate in both rat and dog kidney during acute metabolic acidosis. In the rat, however, after 2 hours, PEPCK activation modifies the kidney metabolite profile. Intrarenal glutamine transport seems to be a rate-limiting factor for adaptation to acute acidosis in the dog but not in the rat kidney.
D000138:Acidosis / Q000201:enzymology / Q000378:metabolism*; D000208:Acute Disease; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D004285:Dogs; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D010071:Oxaloacetates / Q000378:metabolism; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D051381:Rats
D005971:Glutamates; D007656:Ketoglutaric Acids; D008293:Malates; D010071:Oxaloacetates; D005973:Glutamine; D010728:Phosphoenolpyruvate; D000641:Ammonia; D010729:Phosphoenolpyruvate Carboxykinase (GTP)