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Journal of Lipid Research, Vol. 46, 2667-2672, December 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Responses to neither exogenous nor endogenous endothelin-1 are altered in patients with hypercholesterolemia

Lauren M. Boak, Anthony M. Dart, Stephen J. Duffy and Jaye P. F. Chin-Dusting¹

Alfred and Baker Medical Unit, Wynn Domain, Baker Heart Research Institute, Melbourne 3004, Australia

Published, JLR Papers in Press, September 21, 2005. DOI 10.1194/jlr.M500236-JLR200

¹ To whom correspondence should be addressed. e-mail: j.chin{at}alfred.org.au

There is some controversy regarding whether vascular responses to endothelin are altered in hypercholesterolemia. Studies performed to date have been compromised by the use of endothelin antagonists at inappropriate concentrations. In the current study, we examine the role of endothelin-1 in hypercholesterolemic patients using lower, more selective doses of specific endothelin antagonists. Twenty-two patients with hypercholesterolemia (total plasma cholesterol > 6.0 mmol/l) and 17 healthy controls were recruited. Forearm vascular responses to endothelin-1 (5 pmol/min), the endothelin A antagonist BQ-123 (10 nmol/min), and the endothelin B antagonist BQ-788 (1 nmol/min) were obtained. Endothelin-1 caused a significant vasoconstriction in both hypercholesterolemic and control subjects, an effect that was not significantly different between the two groups (P = 0.784). BQ-123 caused a significant vasodilatation that was not significantly different between the two groups (P = 0.899). Similarly, responses to BQ-788 (P = 0.774) and mean plasma endothelin-1 levels were not different (control vs. hypercholesterolemia, 1.16 ± 0.18 vs. 1.06 ± 0.15 fmol/ml; P = 0.64).

Responses to neither exogenous nor endogenous endothelin are influenced by plasma cholesterol levels in humans. It is thus unlikely that the endothelin system contributes to early vascular disease pathology in patients with hypercholesterolemia.

Supplementary key words cholesterol • endothelium • vascular

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