Decreased angiotensin II receptors mediate decreased vascular response in hepatocellular cancer.

Decreased angiotensin II receptors mediate decreased vascular response in hepatocellular cancer.
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血管紧张素 II 受体减少介导肝细胞癌血管反应降低。

DOI:
10.1097/00000658-199602000-00017
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发表时间:
1996
期刊:
影响因子:
9
通讯作者:
Sitzmann,JV
Sitzmann,JV
中科院分区:
医学1区
文献类型:
--
作者:
Wu,Y;Cahill,PA;Sitzmann,JV

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目的通过对正常肝、肝癌、培养肝细胞和H4-IIE细胞血管紧张素II受体状态的评价,探讨血管紧张素II输注在肝癌中升压反应减弱的原因。肿瘤新生血管对血管收缩物质的反应异常,包括对血管紧张素II的反应。肿瘤血管对血管紧张素II的反应改变为调节肿瘤血流量提供了潜在的治疗机会。方法应用放射性微球测定正常肝脏和肿瘤的肝动脉血流量,评价血管紧张素II对肝血管反应的影响。用放射配基结合分析法检测正常肝、肝癌组织、培养肝细胞和H4 IIE细胞的血管紧张素II受体状态,并用生物素标记的血管紧张素II原位结合分析法检测正常肝和肝癌的冰冻切片中血管紧张素II受体的状态。正常肝脏血管紧张素II受体的数量显著高于肝癌(239±20fmol/mg蛋白和162±15fmoL/mg蛋白),而亲和力无明显变化(正常肝脏4.4±0.8 nM,肝癌4.7±1.2 nM)。H4 IIE细胞和原代肝细胞的受体密度较低。原位结合分析显示血管紧张素II受体主要分布在新生血管的平滑肌细胞上。结论血管紧张素II受体在肿瘤新生血管中的缺失可能与血管紧张素II受体的缺失有关。
Objective The authors' objective was to determine the origin of the diminished pressor responsiveness of angiotensin II infusion in hepatoma by evaluating angiotensin II receptor status in normal liver, hepatoma tumor, and cultured hepatocytes and H 4 IIE cells.Summary Background Data Hepatocellular cancer is a highly vascular tumor, where the neovasculature is unique in that it arises only from the hepatic arterial circulation, whereas normal liver has both hepatic arterial and portal venous blood supply. The tumor neovasculature is also characterized by an abnormal vascular reactivity to vasoconstrictors, including the response to angiotensin II. The altered response of tumor vasculature to angiotensin II offers a potential therapeutic opportunity for modulation of tumor blood flow. However, the origin of the decreased vascular response is unknown.Methods The authors evaluated the hepatic vascular response to angiotensin II infusion by determining hepatic arterial blood flow to normal liver and to tumor by means of radioactive microspheres. The angiotensin II receptor status in the normal liver, hepatoma tumor, and cultured hepatocytes and H 4 IIE cells was determined by radioligand binding analysis and in cryostat sections derived from normal liver and hepatoma tumor by means of in situ binding analysis with biotinylated angiotensin II.Results Angiotensin II infusion decreased the hepatic arterial flow to normal liver and increased hepatoma to liver flow ratio. The number of angiotensin II receptors in normal liver was significantly higher than that in hepatoma (239±20 fmol/mg protein in normal liver vs. 162±15 fmol/mg protein in hepatoma) without a change in the affinity (4.4±0.8 nM in normal liver vs. 4.7±1.2 nM in hepatoma). H 4 IIE cells and primary hepatocytes had low receptor density. In situ binding analysis revealed that angiotensin II receptors were mainly on the smooth muscle cells of the neovasculature.Conclusions The data suggests that the diminished vascular response to angiotensin II hepatoma may relate a loss of angiotensin II receptor on tumor neovasculature.
DOI: 10.1016/0022-4804(89)90116-9
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影响因子: --
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通讯作者: Grochow,LB
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DOI: --
发表时间: 1980
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DOI: --
发表时间: 1991
影响因子: 8.8
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DOI: --
发表时间: 1991
期刊: Surgery
影响因子: 3.8
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