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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Disease Models, Animal, Endothelin A Receptor Antagonists, Endothelin B Receptor Antagonists, Femoral Artery, Isoxazoles, Male, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Smooth, Vascular, Myography, Neointima, Pyrrolidines, Thiophenes.
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Does selective endothelin A receptor antagonism with sitaxentan reduce neointimal lesion size in a mouse model of intraluminal injury? Context: Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA / B receptor antagonism at inhibiting neointimal proliferation in a mouse model of intraluminal injury. Antagonism of ETA receptors by sitaxentan (1-100 nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15 mg·kg(-1) ·day(-1) ), A192621 (ETB antagonist; 30 mg·kg(-1) ·day(-1) ), the combination of both antagonists or vehicle. Treatment began 1 week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA / B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions.
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These results suggest that ETA receptor antagonism would be more effective than combined ETA /ETB receptor antagonism at reducing neointimal lesion formation. Final Decision: yes