Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1984838
- author
- Goodwin, Julie E. ; Zhang, Junhui ; Gonzalez, David ; Albinsson, Sebastian LU and Geller, David S.
- organization
- publishing date
- 2011
- 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
- 2016-04-01 10:41:12
- date last changed
- 2022-02-25 04:44:21
@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<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.}},
author = {{Goodwin, Julie E. and Zhang, Junhui and Gonzalez, David and Albinsson, Sebastian and Geller, David S.}},
issn = {{1473-5598}},
keywords = {{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}},
doi = {{10.1097/HJH.0b013e328347da54}},
volume = {{29}},
year = {{2011}},
}