Renal interstitial corticosterone and 11-dehydrocorticosterone in conscious rats

Kristie Usa, Ravinder Jit Singh, Brian C. Netzel, Yong Liu, Hershel Raff, Mingyu Liang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Deficiencies in the conversion between active and inactive glucocorticoids in the kidney can lead to hypertension. However, the significance of glucocorticoid metabolism in specific kidney regions in vivo is not clear, possibly in part due to the difficulty in measuring glucocorticoid levels in kidney regions in vivo. We used microdialysis techniques to sample renal interstitial fluid from conscious rats. The levels of corticosterone (active) and 11-dehydrocorticosterone (inactive) were analyzed by liquid chromatography-tandem mass spectrometry. Direct infusion of the 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibitor carbenoxolone into the renal medulla induced hypertension, and significantly increased corticosterone levels and the corticosterone/11-dehydrocorticosterone ratio, an index of 11β-HSD activity, in the renal medullary microdialysate, but not in urine or the plasma. Further characterization of conscious, untreated rats (n = 13-16) indicated that corticosterone concentrations (ng/ml) 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 corticosterone/11-dehydrocorticosterone ratios were 0.8 ± 0.1, 0.6 ± 0.1, 10.6 ± 1.4, and 1.7 ± 0.1, respectively, in these 4 types of sample. The expression level of 11β-HSD1 was higher in the medulla than in the cortex, whereas 11β-HSD2 was most enriched in the outer medulla. Microdialysate levels of corticosterone were ∼1.6-fold higher in afternoons than in mornings, whereas plasma levels differed by 2.8-fold. These results demonstrated that corticosterone excess in the renal medulla might be sufficient to cause hypertension and provided the first characterization of renal interstitial glucocorticoids.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 2007

Fingerprint

Corticosterone
Kidney
Glucocorticoids
11-beta-Hydroxysteroid Dehydrogenases
Hypertension
Carbenoxolone
Urine
11-dehydrocorticosterone
Extracellular Fluid
Microdialysis
Tandem Mass Spectrometry
Liquid Chromatography

Keywords

  • 11β-hydroxysteroid dehydrogenase
  • Hypertension
  • Mass spectrometry
  • Microdialysis

ASJC Scopus subject areas

  • Physiology

Cite this

Renal interstitial corticosterone and 11-dehydrocorticosterone in conscious rats. / Usa, Kristie; Singh, Ravinder Jit; Netzel, Brian C.; Liu, Yong; Raff, Hershel; Liang, Mingyu.

In: American Journal of Physiology - Renal Physiology, Vol. 293, No. 1, 07.2007.

Research output: Contribution to journalArticle

Usa, Kristie ; Singh, Ravinder Jit ; Netzel, Brian C. ; Liu, Yong ; Raff, Hershel ; Liang, Mingyu. / Renal interstitial corticosterone and 11-dehydrocorticosterone in conscious rats. In: American Journal of Physiology - Renal Physiology. 2007 ; Vol. 293, No. 1.
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