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Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension

Goodwin, Julie E.; Zhang, Junhui; Gonzalez, David; Albinsson, Sebastian LU and Geller, David S. (2011) In Journal of Hypertension 29(7). p.1347-1356
Abstract
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... (More)
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 mm Hg, 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. J Hypertens 29: 1347-1356 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
circadian rhythm, endothelium, mouse model, steroids
in
Journal of Hypertension
volume
29
issue
7
pages
1347 - 1356
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000291480800016
  • pmid:21659825
  • scopus:79958773563
ISSN
1473-5598
DOI
10.1097/HJH.0b013e328347da54
language
English
LU publication?
yes
id
708c0052-fc72-4caa-a502-4e16a99715de (old id 1984838)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21659825?dopt=Abstract
date added to LUP
2011-07-01 09:12:28
date last changed
2017-09-10 03:19:01
@article{708c0052-fc72-4caa-a502-4e16a99715de,
  abstract     = {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 mm Hg, whereas knockout animals have only a 2.7 mmHg increase (P&lt;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. J Hypertens 29: 1347-1356 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams &amp; Wilkins.},
  author       = {Goodwin, Julie E. and Zhang, Junhui and Gonzalez, David and Albinsson, Sebastian and Geller, David S.},
  issn         = {1473-5598},
  keyword      = {circadian rhythm,endothelium,mouse model,steroids},
  language     = {eng},
  number       = {7},
  pages        = {1347--1356},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Hypertension},
  title        = {Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension},
  url          = {http://dx.doi.org/10.1097/HJH.0b013e328347da54},
  volume       = {29},
  year         = {2011},
}