Effect of selective aldosterone deficiency on acidification in nephron segments of the rat inner medulla.
Mineralocorticoid plays a role in urinary acidification and acid-base balance, but the response of the inner medulla to aldosterone has not been elucidated. A model of selective aldosterone deficiency (SAD) with hyperkalemia and hyperchloremic metabolic acidosis was employed to assess segmental acidification by measuring in situ pH, titratable acidity (TA) and total ammonia (Am). Hydrogen ion secretion was also examined as a function of the increment in in situ PCO2 in the collecting duct during bicarbonate loading. SAD rats were compared to ADX controls that received adrenalectomy and chronic replacement of gluco- and mineralocorticoid and to rats with chronic metabolic acidosis induced by oral NH4Cl (CMA). Both fractional and absolute delivery of Am to the loop of Henle was lower in SAD vs. CMA rats (1.34 to 3.63 mM, P less than 0.01). Delivery of Am to the base and tip collecting duct (BCD and TCD) was also markedly lower in SAD (1.50 vs. 0.52 and 1.77 vs. 0.47 mM, respectively, P less than 0.01). Net addition of Am and net acid between BCD and TCD, observed in CMA rats, was not observed in SAD despite equivalent degrees of systemic metabolic acidosis. Similarly, the concentration gradient favoring transfer of NH3 between loop of Henle and CD was reduced in SAD. During bicarbonate loading the increment in PCO2 at BCD, TCD and in final urine was significantly lower in SAD rats than in adrenal intact bicarbonate-loaded rats. Therefore, the acidification defect in this model of SAD appears to be a result of a decrease in ammonia production and delivery to the loop of Henle, impaired transfer from loop to collecting duct and reduction in the rate of H+ secretion by the collecting duct.
DuBose
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Division of Nephrology, University of Texas Medical Branch, Galveston 77550-2778.
Caflisch
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D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000503:physiopathology; D000450:Aldosterone / Q000172:deficiency* / Q000494:pharmacology; D000641:Ammonia / Q000032:analysis; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002712:Chlorides / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004573:Electrolytes / Q000652:urine; D006947:Hyperkalemia / Q000150:complications; D007679:Kidney Medulla / Q000503:physiopathology*; D008138:Loop of Henle / Q000503:physiopathology; D009399:Nephrons / Q000503:physiopathology*; D051381:Rats; D011922:Rats, Mutant Strains
D001639:Bicarbonates; D002712:Chlorides; D004573:Electrolytes; D000450:Aldosterone; D000641:Ammonia; D003907:Dexamethasone