ANGIOTENSIN-II-STIMULATED PROTEIN-SYNTHESIS IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS
ANGIOTENSIN-II-STIMULATED PROTEIN-SYNTHESIS IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS
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DOI：
10.1161/01.hyp.13.4.305
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发表时间：
1989-04-01
期刊：
影响因子：
8.3
通讯作者：
TSUDA, T
中科院分区：
文献类型：
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作者：
BERK, BC;VEKSHTEIN, V;TSUDA, T
为了研究血管收缩激素在血管平滑肌细胞生长中的作用，我们在培养的大鼠主动脉细胞模型中研究了强效血管收缩素II对细胞生长的影响。通过测定细胞数量来评估，血管紧张素II对这些细胞没有促丝性，也没有与10%小牛血清在这方面的协同作用。然而，通过氚化亮氨酸掺入测量，24小时暴露于100 nM血管紧张素II导致蛋白质合成增加80%（与对照组相比增加0.4%）。这是一种“肥厚”反应，蛋白质含量增加30%，细胞体积增加45%。血管紧张素II诱导的平滑肌细胞肥大在100 nM时达到最大，ED50为1 nM，并被竞争拮抗剂[Sar1， Ile8]血管紧张素II抑制。蛋白质合成的增加需要血管紧张素II持续存在6小时，并且需要信使RNA （mRNA）的合成，这表明在暴露于放线菌素d后完全抑制。血管紧张素II刺激的蛋白质合成依赖于细胞内Ca2+浓度的上升，这可以通过25 .mu螯合Ca2+后氚化亮氨酸掺入减少70%来证明。群凌晨2点。该处理未改变10%小牛血清诱导的蛋白质合成。减少细胞外Na+以阻止Na+/H+交换和细胞内碱化不会抑制血管紧张素II反应，但会使10%犊牛血清刺激的蛋白质合成减少35%。12、13-二丁酸佛博尔24小时对蛋白激酶C的下调没有抑制血管紧张素ii诱导的蛋白质合成，而12-肉豆蔻酸13-乙酸佛博尔刺激的蛋白质合成被消除。这些发现表明，血管紧张素ii诱导的肥大，通过Ca2+机制，可能在某些形式的高血压血管平滑肌细胞异常生长中起重要作用。
To investigate the role of vasoconstrictor hormones in vascular smooth muscle cell growth we have studied the effects of the potent vasoconstrictor angiotensin II on cell growth in a cultured rat aortic cell model. Angiotensin II was not mitogenic for these cells, as assessed by determining cell number, nor was it synergistic in this regard with 10% calf serum. However, 24-hour exposure to 100 nM angiotensin II caused an 80% increase in protein synthesis (compared with 0.4% increase with serum control) as measured by tritiated leucine incorporation. This was a "hypertrophic" response as indicated by a 30% increase in protein content and a 45% increase in cell volume. Angiotensin II-induced smooth muscle cell hypertrophy was maximal at 100 nM, had an ED50 of 1 nM, and was inhibited by the competitive antagonist [Sar1, Ile8]angiotensin II. The increase in protein synthesis required continuous presence of angiotensin II for 6 hours and required messenger RNA (mRNA) synthesis as suggested by complete inhibition after exposure to actinomycin D. Angiotensin II-stimulated protein synthesis was dependent on a rise in intracellular Ca2+ concentration evidenced by a 70% decrease in tritiated leucine incorporation after chelation of Ca2+ with 25 .mu.M qun 2-AM. This treatment did not alter protein synthesis induced by 10% calf serum. Decreasing extracellular Na+ to prevent Na+/H+ exchange and intracellular alkalinization did not inhibit the angiotensin II response but decreased the 10% calf serum-stimulated protein synthesis by 35%. Downregulation of protein kinase C by 24-hour treatment with phorbol 12,13-dibutyrate did not inhibit angiotensin II-induced protein synthesis, while phorbol 12-myristate 13-acetate-stimulated protein synthesis was abolished. These findings suggest that angiotensin II-induced hypertrophy, acting via a Ca2+ mechanism, may play an important role in abnormal vascular smooth muscle cell growth in certain forms of hypertension.