title: Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.
abstract: Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ET(A) receptor (BQ123) but not by ET(B) receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ET(A) receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation.
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Justin Wai-Chung
authors.initials: JW
authors.lastname: Leung
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.forename: Hon Wai
authors.initials: HW
authors.lastname: Koon
authors.forename: Fong Ming
authors.initials: FM
authors.lastname: Mo
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Stephen Sum Man
authors.initials: SS
authors.lastname: Chung
authors.forename: Sookja Kim
authors.initials: SK
authors.lastname: Chung
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D004562:Electrocardiography; D042783:Endothelial Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000502:physiology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size
chemical_list: D019332:Endothelin-1
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