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Renal interstitial corticosterone and 11‐dehydrocorticosterone in conscious rats
Author(s) -
Usa Kristie,
Singh Ravinder J.,
Netzel Brian C.,
Liu Yong,
Liang Mingyu
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a893-c
Subject(s) - microdialysis , corticosterone , endocrinology , medicine , chemistry , glucocorticoid , extracellular fluid , kidney , medulla , extracellular , biochemistry , hormone
Genetic or induced abnormalities in the conversion between active and inactive glucocorticoids in the kidney can lead to local glucocorticoid excess and hypertension. It has been difficult, however, to directly assess local glucocorticoid levels in the kidney. We used chronic microdialysis techniques to sample renal cortical and medullary interstitial fluid from conscious rats. The level of corticosterone (compound B, active) and 11‐dehydrocorticosterone (compound A, inactive) was analyzed with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Levels of B (ng/ml, n = 13–16) were 0.8 ± 0.1, 1.0 ± 0.1, 66.7 ± 8.1, and 7.9 ± 1.1 in cortical microdialysate, medullary microdialysate, the plasma, and urine, respectively. The B/A ratio, an index of 11 β‐hydroxysteroid dehydrogenase activity, was 0.8 ± 0.1, 0.6 ± 0.1, 10.6 ± 1.4, and 1.7 ± 0.1, respectively, in those four types of sample. Microdialysate levels of B were approximately 55% higher in afternoons than in mornings, while plasma levels differed by 2.8 fold. An increase of dietary salt content from 0.4% to 4% did not significantly alter levels of B or B/A ratios in renal microdialysate. The protein abundance (fold) of 11 β‐hydroxysteroid dehydrogenase type 2, which inactivates B to A, was 1.0 ± 0.2, 1.6 ± 0.4, and 0.7 ± 0.3 in the cortex, the outer medulla, and the inner medulla, respectively. Type 1 of the enzyme, which likely reactivates A to B, was 1.0 ± 0.1, 1.3 ± 0.2, and 2.0 ± 0.3 in the three regions. Renal interstitial levels of active and inactive glucocorticoids provide an important basis for understanding local metabolism of glucocorticoids in the kidney. (NIH R01HL077263)