Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.
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 E...
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doaj-bdf878c5bcd743a1beff9b3e7cb75f322020-11-24T20:50:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2699410.1371/journal.pone.0026994Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.Justin Wai-Chung LeungWing Tak WongHon Wai KoonFong Ming MoSidney TamYu HuangPaul M VanhoutteStephen Sum Man ChungSookja Kim ChungEndothelin-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.http://europepmc.org/articles/PMC3214015?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Justin Wai-Chung Leung Wing Tak Wong Hon Wai Koon Fong Ming Mo Sidney Tam Yu Huang Paul M Vanhoutte Stephen Sum Man Chung Sookja Kim Chung |
spellingShingle |
Justin Wai-Chung Leung Wing Tak Wong Hon Wai Koon Fong Ming Mo Sidney Tam Yu Huang Paul M Vanhoutte Stephen Sum Man Chung Sookja Kim Chung Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. PLoS ONE |
author_facet |
Justin Wai-Chung Leung Wing Tak Wong Hon Wai Koon Fong Ming Mo Sidney Tam Yu Huang Paul M Vanhoutte Stephen Sum Man Chung Sookja Kim Chung |
author_sort |
Justin Wai-Chung Leung |
title |
Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. |
title_short |
Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. |
title_full |
Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. |
title_fullStr |
Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. |
title_full_unstemmed |
Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. |
title_sort |
transgenic mice over-expressing et-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3214015?pdf=render |
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