Bone medullary arterioles from ovariectomized rats have smaller baseline diameters but normal eNOS expression and NO-mediated dilation.
Bone medullary arterioles from ovariectomized rats have smaller baseline diameters but normal eNOS expression and NO-mediated dilation.
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卵巢切除大鼠的骨髓小动脉具有较小的基线直径，但 eNOS 表达和 NO 介导的扩张正常。
DOI：
10.1016/j.lfs.2004.10.083
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Fleming,JohnT
中科院分区：
文献类型：
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作者：
Soukhova-O'Hare,Galia;Lei,Zhenmin;Falcone,JeffC;Barati,MichelleT;Feitelson,JeremyBA;Rao,ChV;Fleming,JohnT
本研究旨在验证内源性雌激素降低阻力大小骨小动脉内皮型一氧化氮合酶（eNOS）表达，从而降低内皮依赖性血管舒张功能的假设。切除性成熟雌性大鼠卵巢以减少内源性雌激素。将配对的雌性大鼠作为对照。卵巢切除术后7至10天，从股骨髓管收集骨髓组织。免疫组化法检测雌激素受体α、β和eNOS的表达。采用Western blot分析比较骨髓小动脉中eNOS蛋白含量。内皮细胞功能的评估，通过量化的扩张分离，加压骨小动脉对乙酰胆碱的反应。结果表明，去卵巢大鼠和对照大鼠骨微动脉内皮细胞均表达ER-α、ER-β和eNOS。两组小动脉中eNOS蛋白含量无差异。然而，去卵巢大鼠的小动脉基线直径（63±4 μm）显著小于对照大鼠的小动脉直径（75±3 μm，p<0.05）。两组小动脉对乙酰胆碱的反应相同。eNOS的抑制剂L-NAME几乎完全消除了对乙酰胆碱的扩张反应，但对硝普钠没有影响。左旋精氨酸恢复乙酰胆碱诱导的扩张后l-NAME治疗。因此，小动脉扩张乙酰胆碱似乎几乎完全由NO介导。卵巢切除大鼠的小动脉直径较小，表明内源性雌激素对骨小动脉产生显著的扩张影响。然而，扩张剂的影响似乎并不介导的eNOS表达的增加或增强NO依赖性血管舒张。这些结果表明，雌激素不降低eNOS表达或减少NO介导的骨髓小动脉扩张。
This study was designed to test the hypothesis that endogenous estrogens decrease the expression of endothelial nitric oxide synthase (eNOS) in resistance-size bone arterioles, thereby reducing endothelium-dependent vasodilator function. Sexually mature female rats were ovariectomized to reduce endogenous estrogens. Age-matched female rats served as controls. Seven to ten days after ovariectomy, bone marrow tissue was collected from the femoral canal. Immuno-histochemistry was performed to detect expression of estrogen receptors, α and β and eNOS. eNOS protein content in medullary bone arterioles was compared using Western blot analysis. Endothelial cell function was assessed by quantitating the dilation of isolated, pressurized bone arterioles in response to acetylcholine. The results indicate that the endothelium of bone arterioles from ovariectomized and control rats express ER-α, ER-β and eNOS. eNOS protein content in the two groups of arterioles did not differ. However, the baseline diameter of arterioles from ovariectomized rats (63±4 μm) was significantly smaller than the diameter of arterioles from control rats (75±3 μm, p<0.05). The two groups of arterioles dilated equally in response to acetylcholine. l-NAME, an inhibitor of eNOS, almost completely abolished the dilator responses to acetylcholine, but not to sodium nitroprusside. l-Arginine restored acetylcholine-induced dilation after l-NAME treatment. Thus, arteriole dilation to acetylcholine appears to be mediated almost exclusively by NO. The smaller diameter of arterioles from ovariectomized rats suggests that endogenous estrogens exert a significant dilator influence on bone arterioles. However, the dilator influence does not appear to be mediated by an increase in eNOS expression or enhanced NO-dependent vasodilation. These results indicate that estrogens do not decrease eNOS expression or diminish NO-mediated dilation of bone medullary arterioles.