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1 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States
3 Endocrinology and Diabetes, Medical College of Wisconsin/St. Luke's Medical Ctr, Milwaukee, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: liang.pgeditor{at}mcw.edu.
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 11
-hydroxysteroid dehydrogenase (11-HSD) inhibitor carbenoxolone into the renal medulla induced hypertension, and significantly increased corticosterone levels and the corticosterone/11-dehydrocorticosterone ratio, an index of 11-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 11-HSD1 was higher in the medulla than in the cortex, while 11-HSD2 was most enriched in the outer medulla. Microdialysate levels of corticosterone were approximately 1.6 fold higher in afternoons than in mornings, while 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.
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