Adventitia as a source of inducible nitric oxide synthase in the rat aorta.
Adventitia as a source of inducible nitric oxide synthase in the rat aorta.
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DOI：
10.1016/s0895-7061(98)00271-4
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发表时间：
1999-05
影响因子：
3.2
通讯作者：
Hui Zhang;Yue Du;Richard A. Cohen;A. Chobanian;P. Brecher
中科院分区：
文献类型：
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作者：
Hui Zhang;Yue Du;Richard A. Cohen;A. Chobanian;P. Brecher
在当前的研究中，我们使用体外和体内模型来确定细胞因子刺激后大鼠主动脉组织中一氧化氮产生的位点。将完整的大鼠主动脉环与内毒素 (1 μg/mL) 或干扰素-γ (600 U/mL) 一起孵育的体外研究表明，通过 Northern blot 分析或亚硝酸盐产量测定测量，诱导型一氧化氮合酶 (iNOS) 活性的表达增加。原位杂交显示 iNOS mRNA 存在于孵育的主动脉环的内皮和外膜中，但不在中层中。免疫组织化学染色显示 iNOS 蛋白在孵育环中具有类似的定位。还进行了其他研究，其中向大鼠施用细菌内毒素（4 mg/kg），并使用原位杂交和免疫组织化学分析 iNOS 表达。主动脉组织中 iNOS mRNA 和蛋白质明显增加。内皮细胞和外膜细胞是 iNOS 的主要来源，内侧平滑肌中 iNOS mRNA 的含量相对较低，这与体外研究结果一致。这些研究表明主动脉外膜是NO的潜在来源，并表明外膜成纤维细胞在调节动脉结构和功能中可能具有重要的旁分泌作用。 Am J Hypertens 1999；12:467–475 © 1999 American Journal of Hypertension, Ltd.
In the current study we used in vitro and in vivo models to determine the sites of nitric oxide production in rat aortic tissue following cytokine stimulation. In vitro studies in which intact rat aortic rings were incubated with endotoxin (1 μg/mL) or interferon-γ (600 U/mL) indicated that the expression of inducible nitric oxide synthase (iNOS) activity was increased as measured by Northern blot analysis or determination of nitrite production. In situ hybridization showed iNOS mRNA in the endothelium and adventitia of the incubated aortic rings but not in the media. Immunohistochemical staining showed a similar localization for iNOS protein in the incubated rings. Additional studies were performed in which bacterial endotoxin (4 mg/kg) was administered to rats, and iNOS expression was assayed using in situ hybridization and immunohistochemistry. Clear increases in iNOS mRNA and protein were found in aortic tissue. Endothelial and adventitial cells were the major source of iNOS, with relatively low amounts of iNOS mRNA present in medial smooth muscle, consistent with in vitro findings. These studies indicate that the aortic adventitia is a potential source of NO, and suggest that the adventitial fibroblast may have an important paracrine role in regulating arterial structure and function. Am J Hypertens 1999;12:467–475 © 1999 American Journal of Hypertension, Ltd.