title: Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension.
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 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.
  
  
  CONCLUSIONS
  Our study highlights the importance of the vascular endothelial glucocorticoid receptor in several fundamental physiologic processes, namely BP homeostasis and circadian rhythm.
authors.affiliation: Section of Nephrology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA. julie.goodwin@yale.edu
authors.forename: Julie E
authors.initials: JE
authors.lastname: Goodwin
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
authors.forename: David S
authors.initials: DS
authors.lastname: Geller
mesh_terms: D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D017931:DNA Primers; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology*; D006339:Heart Rate; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone