Published Online
on June 26, 2006

A more recent version of this article appeared on August 1, 2006

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Submitted on March 7, 2006
Revised on March 23, 2006

Deletion of Endothelial Cell Endothelin B Receptors Does Not Affect Blood Pressure or Sensitivity to Salt

Alan J. Bagnall^*; Nicholas F. Kelland; Fiona Gulliver-Sloan; Anthony P. Davenport; Gillian A. Gray; Masashi Yanagisawa; David J. Webb; and Yuri V. Kotelevtsev

From the Centre for Cardiovascular Science (A.J.B., N.F.K., F.G.-S., G.A.G., D.J.W., Y.V.K.), University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom; Clinical Pharmacology Unit (A.P.D.), University of Cambridge, Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, United Kingdom; University of Texas Southwestern Medical Center at Dallas (M.Y.).

^* To whom correspondence should be addressed. E-mail: Alan.Bagnall{at}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.

Key words: endothelin • mice • endothelium • receptors, endothelin • vasodilation

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