Document Detail


Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension.
MedLine Citation:
PMID:  21659825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Glucocorticoid-mediated hypertension is incompletely understood. Recent studies have suggested the primary mechanism of this form of hypertension may be through the effects of glucocorticoids on vascular tissues and not to excess sodium and water re-absorption as traditionally believed.
OBJECTIVE: The goal of this study was to better understand the role of the vasculature in the generation and maintenance of glucocorticoid-mediated hypertension.
METHODS: We created a mouse model with a tissue-specific knockout of the glucocorticoid receptor in the vascular endothelium.
RESULTS: We show that these mice are relatively resistant to dexamethasone-induced hypertension. After 1 week of dexamethasone treatment, control animals have a mean blood pressure (BP) increase of 13.1 mmHg, whereas knockout animals have only a 2.7 mmHg increase (P < 0.001). Interestingly, the knockout mice have slightly elevated baseline BP compared with the controls (112.2 ± 2.5 vs. 104.6 ± 1.2 mmHg, P = 0.04), a finding which is not entirely explained by our data. Furthermore, we demonstrate that the knockout resistance arterioles have a decreased contractile response to dexamethasone with only 6.6% contraction in knockout vessels compared with 13.4% contraction in control vessels (P = 0.034). Finally, we show that in contrast to control animals, the knockout animals are able to recover a significant portion of their normal circadian BP rhythm, suggesting that the vascular endothelial glucocorticoid receptor may function as a peripheral circadian clock.
CONCLUSION: Our study highlights the importance of the vascular endothelial glucocorticoid receptor in several fundamental physiologic processes, namely BP homeostasis and circadian rhythm.
Authors:
Julie E Goodwin; Junhui Zhang; David Gonzalez; Sebastian Albinsson; David S Geller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-10     Completed Date:  2011-10-13     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1347-56     Citation Subset:  IM    
Affiliation:
Section of Nephrology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA. julie.goodwin@yale.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Blood Pressure
DNA Primers
Dexamethasone / administration & dosage*
Disease Models, Animal
Endothelium, Vascular / physiology*
Heart Rate
Hypertension / chemically induced,  physiopathology*
Mice
Mice, Knockout
Receptors, Glucocorticoid / genetics,  physiology
Grant Support
ID/Acronym/Agency:
K08 DK078623/DK/NIDDK NIH HHS; K08-DK078623/DK/NIDDK NIH HHS; P30AR053495/AR/NIAMS NIH HHS; U24 DK59635/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Receptors, Glucocorticoid; 50-02-2/Dexamethasone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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