Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure
Key result
Long-term treatment with ET-receptor antagonists significantly improved acetylcholine-induced relaxation in rats with chronic MI, with LU 135252 being more effective than Bosentan.
Why the study?
Does endothelin-receptor blockade improve endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction?
Population
Wistar rats 12 weeks after extensive myocardial infarction compared to sham-operated animals
Comparison
Selective ET-receptor antagonist LU 135252 or… vs Placebo
Design
Preclinical
Follow-up
12 weeks
Authors
Discussion
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Implication
Hypothesis-generating for selective ET(A) blockade in post-MI endothelial dysfunction; requires clinical confirmation before translation.
Key Points
- To elucidate the effects of selective endothelin ET(A)- and mixed ET(A/B)-receptor antagonists on endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction.
- Wistar rats were assessed 12 weeks after undergoing extensive myocardial infarction (>46% left ventricular involvement) or sham surgery.
- Rats received chronic therapy with either the selective ET(A) antagonist LU 135252 (30 mg/kg/day), the mixed ET(A/B) antagonist bosentan (100 mg/kg/day), or placebo.
- Vasoreactivity, nitric oxide-mediated relaxation, aortic superoxide anion production, and plasma renin activity were measured across all cohorts.
- Endothelium-dependent relaxation induced by acetylcholine was significantly reduced in untreated post-infarction rats, but long-term administration of both receptor antagonists significantly improved relaxation, with LU 135252 showing superior efficacy over bosentan.
- Aortic superoxide anion formation and plasma renin activity were significantly elevated in heart failure rats and were completely normalized by LU 135252, whereas bosentan had no corrective effect on either parameter.
- Endothelium-independent vasodilation induced by sodium nitroprusside and contractile responses to endothelin and phenylephrine did not differ between the experimental groups.
Structured PICO
Does endothelin-receptor blockade improve endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction?
P
Population
Wistar rats evaluated 12 weeks after extensive myocardial infarction (>46% of left ventricle) compared to sham-operated animals.
I
Intervention
Selective ET(A)-receptor antagonist LU 135252 (30 mg/kg/day) or mixed ET(A/B)-receptor antagonist Bosentan (100 mg/kg/day)
C
Comparator
Placebo
O
Outcome
Vasoreactivity (endothelium-dependent, nitric oxide-mediated relaxation induced by acetylcholine) and superoxide anion formation in aortic ringssurrogate
Endothelin-receptor blockade, particularly selective ET(A) antagonism, improves endothelial vasomotor dysfunction and reduces oxidative stress in a rat model of post-MI heart failure.
Cite This Study
Johann Bauersachs (2000) studied Heart failure after myocardial infarction. LU 135252 and Bosentan vs. Placebo was evaluated on Endothelium-dependent, nitric oxide-mediated relaxation induced by acetylcholine. Long-term treatment with ET-receptor antagonists significantly improved acetylcholine-induced relaxation in rats with chronic MI, with LU 135252 being more effective than Bosentan.