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Am J Physiol Cell Physiol 286: C1019-C1030, 2004. First published December 24, 2003; doi:10.1152/ajpcell.00394.2003
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin

Hassane Amlal,1 Sulaiman Sheriff,2 and Manoocher Soleimani1,3

Departments of 1Internal Medicine and 2Surgery, University of Cincinnati School of Medicine, and 3Veterans Affairs Medical Center, Cincinnati, Ohio 45267-0585

Submitted 16 September 2003 ; accepted in final form 22 December 2003

Metabolic acidosis is associated with alteration in fluid and electrolyte reabsorption in a number of nephron segments. However, the effects of metabolic acidosis on urine osmolality and aquaporin-2 (AQP-2) remain poorly understood. In these studies, we examined the effects of chronic metabolic acidosis on water handling by the kidney. Rats were placed in metabolic cages and subjected to water (control) or 280 mM NH4Cl loading for 120 h to induce metabolic acidosis. The results indicated a significant increase in urine osmolality with no change in urine volume or urinary Na+ excretion in acid-loaded animals. This effect was independent of alteration in fluid intake or salt/Cl- loading. Immunoblotting and Northern hybridization studies indicated that AQP-2 protein abundance and mRNA expression levels increased significantly along the collecting duct system of NH4Cl-but not NaCl-loaded animals. RIA results indicated that metabolic acidosis was associated with a fourfold increase in circulating levels of vasopressin (AVP) and a significant increase in brain AVP mRNA expression levels. In conclusion, metabolic acidosis upregulates the expression levels of AQP-2 and increases urine osmolality, suggesting an adaptive increase in water reabsorption in the collecting duct. A concomitant increase in AVP synthesis and secretion likely plays an essential role in the adaptation of AQP-2 in metabolic acidosis.

kidney; acid-base; urine osmolality; sodium excretion rate


Address for reprint requests and other correspondence: H. Amlal, 231 Albert Sabin Way, MSB (Rm. G-259), Cincinnati, OH 45267-0585 (E-mail: hassane.amlal{at}uc.edu).




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