Adaptive Responses to Dexamethasone Treatment in Rat Kidney Proximal Tubules

Lee, Song Eun; Nam, Kwang Il; Bae, Choon Sang; Kim, Baik Yoon; Park, Sung Sik; Ahn, Kyu Youn

Abstract

Excess accumulation of glucocorticoid increases acid secretion and HCO3- reabsorption in the kidney. Reabsorption of HCO3-, which almost occurs at the proximal tubule, is mediated Na+ / H+ exchanger-3 (NHE-3) and H+ -ATPase on the apical membrane and the Na + /HCO3- cotransporter-1 (NBC-1)on the basolateral membrane. Impact of glucocorticoid was investigated by immunohistochemistry and electron microscopy to correlate the changes with the effect of in vivo dexamethasone treatment for the rat kidney proximal tubule. In a control group, immunoreactivity of NHE-3 was detected in the apical membrane and the brush borders of S1, S2 and 3 segments of the proximal tubule. Immunoreactivity of NBC-1 was detected in the basolateral membrane of S1 and S2 segments of the proximal tubule. Immunoreactivity of NHE-3 and NBC-1 protein was more pronounced in dexamethasone treated groups than the control group. Dexamethasone 1 mg/kg caused most intense immunoreactivity for NHE-3 and NBC-1 protein, however, 0.01 mg/kg and 0.1 mg/kg produced less intense immunoreactivity with no appreciable differences between these lower doses of dexamethasone groups. By electron microscopy, the tubular cells of S1 segment of the control group revealed numerous mitochondria, endocytic apparatuses, lysosomes and many basal cytoplasmic processes. In dexamethasone treated groups, the cells of S1 and S2 segments of the proximal tubule had more mitochodria and more basolateral invaginations and had an increased number of more elongated microvilli, compared with the control group. The cells of the S3 segment of the control group showed scant lateral interdigitations and had a few smaller mitochondria. The cells of the S3 segment of dexamethasone treated groups had many mitochodria and an increased number of microvilli in the brush border, but revealed no difference of basolateral invaginations among the different groups of dexamethasone. These results indicate that prolonged administration of excess glucocorticoid increases NHE-3 and NBC-1 protein, and the up-regulation of these proteins could result in increased HCO3 - reabsorption in the rat renal proximal tubules. It also suggests that these adaptive responses closely correlate to morphological alterations of proximal tubular epithelial cells.