| First Author | Goodwin JE | Year | 2011 |
| Journal | J Hypertens | Volume | 29 |
| Issue | 7 | Pages | 1347-56 |
| PubMed ID | 21659825 | Mgi Jnum | J:242123 |
| Mgi Id | MGI:5904461 | Doi | 10.1097/HJH.0b013e328347da54 |
| Citation | Goodwin JE, et al. (2011) Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension. J Hypertens 29(7):1347-56 |
| abstractText | 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. |
