a-192621 has been researched along with Neointima* in 2 studies
2 other study(ies) available for a-192621 and Neointima
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Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury.
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.. These results suggest that ETA receptor antagonism would be more effective than combined ETA /ETB receptor antagonism at reducing neointimal lesion formation. Topics: 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 | 2015 |
Non-endothelial cell endothelin-B receptors limit neointima formation following vascular injury.
The potent vasoconstrictor endothelin-1 (ET-1), acting on the endothelin-A (ETA) receptor, promotes intimal lesion formation following vascular injury. The endothelin-B (ETB) receptor, which mediates nitric oxide release and ET-1 clearance in endothelial cells, may moderate lesion formation, but this is less clear. We used selective ET receptor antagonists and cell-specific deletion to address the hypothesis that ETB receptors in the endothelium inhibit lesion formation following arterial injury.. Neointimal proliferation was induced by wire or ligation injury to the femoral artery in mice treated with selective ETA (ABT-627) and/or ETB antagonists (A192621). Measurement of lesion formation by optical projection tomography and histology indicated that ETA blockade reduced lesion burden in both models. Although ETB blockade had little effect on ligation injury-induced lesion formation, after wire injury, blockade of the ETB receptor increased lesion burden (184% of vehicle; P < 0.05) and reversed the protective effects of an ETA antagonist. Selective deletion of ETB receptors from the endothelium, however, had no effect on neointimal lesion size.. These results are consistent with ETB receptor activation playing an important role in limiting neointimal lesion formation following acute vascular injury, but indicate that this protective effect is not mediated by those ETB receptors expressed by endothelial cells. These data support the proposal that selective ETA antagonists may be preferable to mixed ETA/ETB antagonists for targeting the arterial response to injury. Topics: Animals; Blood Pressure; Endothelin B Receptor Antagonists; Endothelin-1; Male; Mice; Mice, Inbred C57BL; Neointima; Pyrrolidines; Receptor, Endothelin A; Receptor, Endothelin B; Vascular System Injuries | 2012 |