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Hypertension. 2006 Aug;48(2):286-93. Epub 2006 Jun 26.

Deletion of endothelial cell endothelin B receptors does not affect blood pressure or sensitivity to salt.

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  • 1Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Little France Crescent, Edinburgh, EH16 4TJ United Kingdom. Alan.Bagnall@ed.ac.uk

Abstract

Endothelin B receptors in different tissues regulate diverse physiological responses including vasoconstriction, vasodilatation, clearance of endothelin-1, and renal tubular sodium reabsorption. To examine the role of endothelial cell endothelin B receptors in these processes, we generated endothelial cell-specific endothelin B receptor knockout mice using a Cre-loxP approach. We have demonstrated loss of endothelial cell endothelin B receptor expression and function and preservation of nonendothelial endothelin B receptor-mediated responses through binding and functional assays. Ablation of endothelin B receptors exclusively from endothelial cells produces endothelial dysfunction in the absence of hypertension, with evidence of decreased endogenous release of NO and increased plasma endothelin-1. In contrast to models of total endothelin B receptor ablation, the blood pressure response to a high-salt diet is unchanged in endothelial cell-specific endothelin B receptor knockouts compared with control floxed mice. These findings suggest that the endothelial cell endothelin B receptor mediates a tonic vasodilator effect and that nonendothelial cell endothelin B receptors are important for the regulation of blood pressure.

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PMID:
16801484
[PubMed - indexed for MEDLINE]
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