Submitted on June 9, 2005
Revised on September 9, 2005
Accepted on September 21, 2005
Neither responses to exogenous nor endogenous endothelin-1 are altered in patients with hypercholesterolemia
Lauren M. Boak, Anthony M. Dart, Stephen Duffy, and Jaye P. F. Chin-Dusting
Baker Heart Research Institute, Melbourne, Victoria 3004
Corresponding Author: jaye.chin-dusting{at}baker.edu.au
ABSTRACT Objective: There is some controversy as to whether vascular responses to endothelin are altered in patients with hypercholesterolemia. Studies performed thus far have been compromised by the use of endothelin antagonists at concentrations which have been reported to be both nonselective and systemically active. In the current study, we examine the role of both exogenous and endogenous endothelin-1 responses in patients with hypercholesterolemia using lower, more selective doses of the specific endothelin antagonists. Methods and results: 22 patients with hypercholesterolemia (total plasma cholesterol >6.0 mmol/L) and 17 controls (total plasma cholesterol < 5.5 mmol.L) were recruited into the study. Forearm vascular responses to endothelin-1 (5 pmol/min), the endothelin-A receptor antagonist, BQ-123 (10 nmol/min) and the endothelin-B receptor antagonist, BQ-788 (1 nmol/min) were obtained using venous occlusion plethysmography. All participants underwent at least one of the drug infusion protocols. Endothelin-1 caused a significant vasoconstrictor response in both hypercholesterolemic and control subjects; an effect which was not significantly different between the 2 groups (2-way repeated measures ANOVA; p=0.784). BQ-123 caused a significant vasodilatory response which was not significantly different between the 2 groups (p=0.899). Similarly, responses to BQ-788 (p=0.774) and mean plasma endothelin-1 levels were not different between the 2 groups (control vs hypercholesterolemia: 1.16 + 0.18 fmol/ml vs 1.06 + 0.15 fmol/ml; p=0.64) Conclusions: Responses to neither exogenous nor endogenous endothelin are influenced by plasma cholesterol levels in man. It is thus unlikely that the endothelin system contributes to early vascular disease pathology in patients with hypercholesterolemia.
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