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Uninephrectomy reduces 11β-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats.
MedLine Citation:
PMID:  22739210     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Renal allograft donors are at risk to develop hypertension. Here we hypothesized that this risk is at least in part explained by an enhanced intracellular availability of 11β-hydroxyglucocorticoids due to an increased 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), an intracellular prereceptor activator of biologically inactive 11-ketocorticosteroids in the liver and/or a diminished 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an inactivator of 11β-hydroxyglucocorticoids in the kidney.METHODS: To test this hypothesis uninephrectomized (n=9) (UNX) and sham-operated (n=10) adult Sprague-Dawley rats were investigated. Mean arterial blood pressure and heart rate were measured continuously by telemetry for 6 days in week five after UNX. The mRNA of 11β-HSD1 and 11β-HSD2 were assessed by RT-PCR in liver and kidney tissue and the 11β-HSD activities directly quantified in their corresponding tissues by determining the ratios of (tetrahydrocorticosterone+5α-tetrahydrocorticosterone)/tetrahydrodehydrocorticosterone [(THB+5α-THB)/THA] and of corticosterone/dehydrocorticosterone (B/A) by gas chromatography-mass spectrometry. The apparent total body activities of 11β-HSD1 and 11β-HSD2 were estimated using the urinary and plasma ratios of (THB+5α-THB)/THA and B/A.RESULTS: Mean arterial blood pressure was increased after UNX when compared to sham-operation. Hepatic mRNA content of 11β-HSD1 and hepatic, plasma and urinary ratios of (THB+5α-THB)/THA were decreased after UNX, indicating diminished access of glucocorticoids to glucocorticoid receptors. In renal tissue 11β-HSD2 mRNA was reduced and B/A ratios measured in kidney, plasma and urine were increased, indicating reduced 11β-HSD2 activity and enhanced access of glucocorticoids to mineralocorticoid receptors.CONCLUSIONS: Both 11β-HSD1 and 11β-HSD2 are down regulated after UNX in rats, a constellation considered to induce hypertension.
Authors:
Meret Lauterburg; Geneviève Escher; Bernhard Dick; Daniel Ackermann; Felix Frey
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-27
Journal Detail:
Title:  The Journal of endocrinology     Volume:  -     ISSN:  1479-6805     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
M Lauterburg, Nephrology, Inselspital, Bern, Switzerland.
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