Long-term administration of endothelin receptor antagonist improves coronary endothelial function in patients with early atherosclerosis

Martin Reriani, Eugenia Raichlin, Abhiram Prasad, Verghese Mathew, Geralyn M. Pumper, Rebecca E. Nelson, Ryan Lennon, Charanjit Rihal, Lilach O. Lerman, Amir Lerman

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Background-: Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ETA) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Methods and results-: Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ETA receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10-6 to 10-4 mol/L) in the left anterior descending coronary artery. NG-monomethyl-L-arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus-2.22%, 95% confidence interval-27.37% to 15.28%; P<0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N-monomethyl-l-arginine were similar between the groups at baseline and at 6 months. Conclusions-: This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans.

Original languageEnglish (US)
Pages (from-to)958-966
Number of pages9
JournalCirculation
Volume122
Issue number10
DOIs
StatePublished - Sep 7 2010

Keywords

  • blood flow
  • coronary disease
  • endothelin
  • endothelium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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