Long-Term Administration of Endothelin Receptor Antagonist Improves Coronary Endothelial Function in Patients With Early Atherosclerosis

• Published in: Circulation (New York, N.Y.) N.Y.), 2010-09, Vol.122 (10), p.958-966
• Main Authors: RERIANI, Martin, RAICHLIN, Eugenia, PRASAD, Abhiram, MATHEW, Verghese, PUMPER, Geralyn M, NELSON, Rebecca E, LENNON, Ryan, RIHAL, Charanjit, LERMAN, Lilach O, LERMAN, Amir
• Format: Article
• Language: English
• Subjects: Adult; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - drug effects; Blood Pressure - drug effects; Cardiology. Vascular system; Coronary Artery Disease - drug therapy; Coronary Artery Disease - metabolism; Coronary Circulation - drug effects; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelin-1 - antagonists & inhibitors; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - administration & dosage; Female; Follow-Up Studies; Heart Rate - drug effects; Humans; Kidney - drug effects; Lipoprotein(a) - blood; Male; Medical sciences; Microcirculation - drug effects; Middle Aged; Nitric Oxide - metabolism; omega-N-Methylarginine - administration & dosage; Pyrrolidines - administration & dosage; Pyrrolidines - adverse effects; Receptor, Endothelin A - metabolism; Triglycerides - blood; Uric Acid - blood
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.110.967406

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 (ET(A)) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. 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 ET(A) 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. N(G)-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