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Abstract：
BACKGROUND: Angiotensin II (Ang II) has diverse effects on smooth muscle cells (SMCs). The diversity of effects may relate to the regional location of this cell type.
OBJECTIVE: The aim of this study was to define whether Ang II exerted divergent effects on smooth muscle cells in the aorta and determine the role of blood pressure and specific oxidant mechanisms.
RESULTS: Ang II (1000 ng/kg per minute) infusion for 28 days into mice increased systolic blood pressure and promoted medial expansion of equivalent magnitude throughout the entire aorta. Both effects were ablated by angiotensin II type 1a (AT(1a)) receptor deficiency. Similar increases in systolic blood pressure by administration of norepinephrine promoted no changes in aortic medial thickness. Increased medial thickness was attributable to SMC expansion owing to hypertrophy in most aortic regions, with the exception of hyperplasia of the ascending aorta. Deficiency of the p47(phox) component of NADPH oxidase ablated Ang II-induced medial expansion in all aortic regions. Analysis of mRNA and protein throughout the aorta revealed a much higher abundance of the inhibitor of differentiation 3 (Id3) in the ascending aorta compared to all other regions. A functional role was demonstrated by Id3 deficiency inhibiting Ang II-induced SMC hyperplasia of the ascending aorta.
CONCLUSIONS: In conclusion, Ang II promotes both aortic medial hypertrophy and hyperplasia in a region-specific manner via an oxidant mechanism. The ascending aortic hyperplasia is dependent on Id3.
OBJECTIVE: The aim of this study was to define whether Ang II exerted divergent effects on smooth muscle cells in the aorta and determine the role of blood pressure and specific oxidant mechanisms.
RESULTS: Ang II (1000 ng/kg per minute) infusion for 28 days into mice increased systolic blood pressure and promoted medial expansion of equivalent magnitude throughout the entire aorta. Both effects were ablated by angiotensin II type 1a (AT(1a)) receptor deficiency. Similar increases in systolic blood pressure by administration of norepinephrine promoted no changes in aortic medial thickness. Increased medial thickness was attributable to SMC expansion owing to hypertrophy in most aortic regions, with the exception of hyperplasia of the ascending aorta. Deficiency of the p47(phox) component of NADPH oxidase ablated Ang II-induced medial expansion in all aortic regions. Analysis of mRNA and protein throughout the aorta revealed a much higher abundance of the inhibitor of differentiation 3 (Id3) in the ascending aorta compared to all other regions. A functional role was demonstrated by Id3 deficiency inhibiting Ang II-induced SMC hyperplasia of the ascending aorta.
CONCLUSIONS: In conclusion, Ang II promotes both aortic medial hypertrophy and hyperplasia in a region-specific manner via an oxidant mechanism. The ascending aortic hyperplasia is dependent on Id3.
摘要：
背景：血管紧张素II（AngII）对平滑肌细胞（SMC）具有多种作用。影响的多样性可能与这种细胞类型的区域位置有关。
目的：这项研究的目的是确定AngII是否对主动脉平滑肌细胞产生不同的影响，并确定血压和特定的氧化机制的作用。
结果：AngII（每分钟1000ng/kg）输注28天，可增加小鼠的收缩压，并促进整个主动脉的内侧扩张。血管紧张素II1a型（AT（1a））受体缺乏症消除了两种作用。通过施用去甲肾上腺素引起的收缩压相似的增加不会促进主动脉中层厚度的变化。由于大多数主动脉区域的肥大，中层厚度增加可归因于SMC扩张。除了升主动脉的增生。NADPH氧化酶的p47（phox）成分的缺乏消融了AngII诱导的所有主动脉区域的内侧扩张。对整个主动脉的mRNA和蛋白质的分析显示，与所有其他区域相比，升主动脉中分化抑制剂3（Id3）的丰度要高得多。Id3缺乏抑制AngII诱导的升主动脉SMC增生证明了其功能作用。
结论：结论：AngII通过氧化剂机制以区域特异性方式促进主动脉内侧肥大和增生。升主动脉增生依赖于Id3。
目的：这项研究的目的是确定AngII是否对主动脉平滑肌细胞产生不同的影响，并确定血压和特定的氧化机制的作用。
结果：AngII（每分钟1000ng/kg）输注28天，可增加小鼠的收缩压，并促进整个主动脉的内侧扩张。血管紧张素II1a型（AT（1a））受体缺乏症消除了两种作用。通过施用去甲肾上腺素引起的收缩压相似的增加不会促进主动脉中层厚度的变化。由于大多数主动脉区域的肥大，中层厚度增加可归因于SMC扩张。除了升主动脉的增生。NADPH氧化酶的p47（phox）成分的缺乏消融了AngII诱导的所有主动脉区域的内侧扩张。对整个主动脉的mRNA和蛋白质的分析显示，与所有其他区域相比，升主动脉中分化抑制剂3（Id3）的丰度要高得多。Id3缺乏抑制AngII诱导的升主动脉SMC增生证明了其功能作用。
结论：结论：AngII通过氧化剂机制以区域特异性方式促进主动脉内侧肥大和增生。升主动脉增生依赖于Id3。
