Vasodilation of intramuscular arterioles under shear stress in dystrophin-deficient skeletal muscle is impaired through decreased nNOS expression.
Vasodilation of intramuscular arterioles under shear stress in dystrophin-deficient skeletal muscle is impaired through decreased nNOS expression.
复制标题
在肌营养不良蛋白缺乏的骨骼肌中，剪切应力下肌内小动脉的血管舒张功能会因 nNOS 表达减少而受损。
作者：
K. Sato;T. Yokota;S. Ichioka;M. Shibata;S. Takeda
杜氏肌营养不良症（DMD）是一种致命的横纹肌x连锁疾病，由肌营养不良蛋白缺乏引起。近年来，在DMD中发现了剪切应力对血管扩张的损害，但其潜在的分子机制尚不完全清楚。此外，肌内小动脉的扩张可能是分子发病的关键，但尚未得到解决。我们观察了由于结扎引起的剪应力下小鼠胸肌小动脉的扩张。肌营养不良蛋白缺陷小鼠和神经元型一氧化氮合酶（nNOS）缺陷小鼠的血管舒张功能明显受损；然而，内皮nos缺陷小鼠和α 1-syntrophin缺陷小鼠在血管舒张方面与对照小鼠没有任何差异。这些结果表明，在剪切应力诱导的骨骼肌血管舒张中，nNOS是一氧化氮的主要供应者，但nNOS的肌层定位并不是必不可少的。相比之下，mdx或nnos缺陷小鼠对乙酰胆碱或硝普钠的反应并未受损，这表明使用血管活性药物进行药物治疗可能改善DMD的骨骼和心肌症状。
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder of striated muscle caused by the absence of dystrophin. Recently, impairment of vascular dilation under shear stress has been found in DMD, but the underlying molecular mechanism is not fully understood. Moreover, dilation of intramuscular arterioles, which may be a key to the molecular pathogenesis, has not been addressed yet. We examined dilation of arterioles in the mouse cremaster muscle under shear stress due to ligation. The vasodilation was significantly impaired in dystrophin-deficient mdx mice as well as in neuronal nitric oxide synthase (nNOS)-deficient mice; however, neither endothelial NOS-deficient mice nor alpha1-syntrophin-deficient mice showed any difference in vasodilation from control mice. These results indicate that nNOS is the main supplier of nitric oxide in shear stress-induced vasodilation in skeletal muscle, but that the sarcolemmal localization of nNOS is not indispensable for the function. In contrast, the response to acetylcholine or sodium nitroprusside was not impaired in mdx or nNOS-deficient mice, suggesting that pharmacological treatment using a vasoactive agent may ameliorate skeletal and cardiac muscle symptoms of DMD.
影响因子：
20.1
作者：
KOLLER, A;SUN, D;KALEY, G
通讯作者：
KALEY, G