Inducible human endothelin-1 overexpression in endothelium raises blood pressure via endothelin type A receptors.
Hypertension
; 66(2): 347-55, 2015 Aug.
Article
de En
| MEDLINE
| ID: mdl-26101346
ABSTRACT
The mechanisms of blood pressure regulation by endothelin-1 produced by endothelial cells are complex and still unclear. Transgenic mice with endothelium-restricted human endothelin-1 (EDN1) overexpression presented vascular damage but no significant change in blood pressure, which could be because of adaptation to life-long exposure to elevated endothelin-1 levels. We now generated a tamoxifen-inducible endothelium-restricted EDN1 overexpressing transgenic mouse (ieET-1) using Cre/loxP technology. Sixteen days after tamoxifen treatment, ieET-1 mice presented ≥10-fold increase in plasma endothelin-1 (P<0.01) and ≥20 mm Hg elevation in systolic blood pressure (P<0.01), which could be reversed by atrasentan (P<0.05). Endothelin-1 overexpression did not cause vascular or kidney injury or changes in kidney perfusion or function. However, endothelin type A and B receptor expression was differentially regulated in the mesenteric arteries and the kidney. Our results demonstrate using this ieET-1 mouse model that 21 days of induction of endothelin-1 overexpression caused endothelin-1-dependent elevated blood pressure mediated by endothelin type A receptors.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pression sanguine
/
Endothélium vasculaire
/
Régulation positive
/
Endothéline-1
/
Récepteur de type A de l'endothéline
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Hypertension
Année:
2015
Type de document:
Article