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Assessing Endothelial Vasodilator Function with the Endo-PAT 2000
Published on: October 16, 2010
Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure.
J Bauersachs1, D Fraccarollo, P Galuppo
1Medizinische Klinik der Julius-Maximilians-Universität Würzburg and II. Medizinische Klinik, Universitätsklinikum Mannheim, Mannheim, Germany. j.bauersachs@medizin.uni-weurzburg.de
Cardiovascular Research
|June 28, 2000
Summary
Endothelin receptor antagonists improved endothelial dysfunction in rats with heart failure after myocardial infarction (MI). Selective ET(A) blockade with LU 135252 showed greater efficacy than mixed ET(A/B) blockade with Bosentan.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Endocrinology
Background:
- Heart failure following myocardial infarction (MI) is associated with endothelial vasomotor dysfunction.
- Endothelin (ET) receptor pathways play a role in the pathophysiology of heart failure.
Purpose of the Study:
- To investigate the effects of selective endothelin ET(A)-receptor antagonists and mixed ET(A/B)-receptor antagonists on endothelial vasomotor dysfunction in a rat model of chronic heart failure post-MI.
- To compare the efficacy of a selective ET(A) antagonist (LU 135252) versus a mixed ET(A/B) antagonist (Bosentan).
Main Methods:
- Wistar rats underwent extensive MI or sham operation.
- Twelve weeks post-MI, aortic rings were assessed for vasoreactivity and superoxide anion formation.
- Rats were treated long-term with LU 135252 (selective ET(A)), Bosentan (mixed ET(A/B)), or placebo.
Main Results:
- MI rats exhibited impaired endothelium-dependent relaxation to acetylcholine and increased aortic superoxide formation.
- Both LU 135252 and Bosentan significantly improved acetylcholine-induced relaxation in MI rats.
- LU 135252 demonstrated superior efficacy, normalizing superoxide formation and improving relaxation more effectively than Bosentan.
- Endothelium-independent relaxations and agonist-induced contractions were similar across groups.
Conclusions:
- Long-term treatment with endothelin receptor antagonists ameliorates endothelial vasomotor dysfunction in chronic heart failure post-MI.
- Selective ET(A) receptor blockade appears to be a promising therapeutic strategy, potentially offering greater benefits than mixed ET(A/B) blockade.
- The improvement in endothelial function may be a key mechanism underlying the beneficial effects of ET receptor blockade in heart failure.
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