Obesity and heterozygous endothelial overexpression of prepro-endothelin-1 modulate responsiveness of mouse main and segmental renal arteries to vasoconstrictor agents.
Life Sci
; 118(2): 206-12, 2014 Nov 24.
Article
em En
| MEDLINE
| ID: mdl-24412387
ABSTRACT
AIMS:
Levels of the endothelium-derived peptide endothelin-1 (ET-1) are elevated in obese humans, and ET-1 mediated vascular tone is increased. Renal arterial smooth muscle is highly responsive to ET-1. Whether or not endothelium-derived ET-1 affects contractions of the renal artery under normal conditions or in obesity is unknown. The present study was designed to investigate whether or not overexpression of endogenous ET-1 in the endothelium affects the responsiveness of the main and segmental renal arteries differently in obesity. MAINMETHODS:
Mice with tie-1 promoter-driven endothelium-restricted heterozygous overexpression of preproendothelin-1 were used (TET(het)). Obesity was induced in TET(het) mice and wild-type (WT) littermates by feeding a high fat diet for 30 weeks; lean controls were kept on standard chow. The renal arteries were studied in wire myographs testing contractions (in the presence of l-NAME) to ET-1, serotonin, and U46619. KEYFINDINGS:
Contractions to ET-1 were comparable between groups in main renal arteries, but augmented in segmental preparations from obese mice. Serotonin-induced responses were enhanced in obese TET(het) mice renal arteries compared to lean controls. Concentration-contraction curves to U46619 were shifted significantly to the left in main renal arteries of obese animals, and the maximal response was significantly increased between lean and obese TET(het) mice.SIGNIFICANCE:
These results indicate an augmented responsiveness of main renal arteries in obesity particularly to TP receptor activation. When combined with endothelial ET-1 overexpression this effect is even more pronounced, which may help to gain further insights into the mechanisms of hypertension in obesity.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Artéria Renal
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Vasoconstritores
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Endotelina-1
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Obesidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article