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(Hypertension. 2006;48:286.)
© 2006 American Heart Association, Inc.

Original Articles

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; 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.).

Correspondence to Alan Bagnall, Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Little France Crescent, Edinburgh, EH16 4TJ United Kingdom. E-mail Alan.Bagnall{at}ed.ac.uk

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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Clarifying Endothelin Type B Receptor Function

David M. Pollock and Markus P. Schneider
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