Angiotensin II-induced aortic ring constriction is mediated by phosphatidylinositol 3-kinase/L-type calcium channel signaling pathway
Angiotensin II-induced aortic ring constriction is mediated by phosphatidylinositol 3-kinase/L-type calcium channel signaling pathway
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DOI：
10.3858/emm.2009.41.8.062
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发表时间：
2009-08-31
影响因子：
12.8
通讯作者：
Bae, Sun Sik
中科院分区：
文献类型：
--
作者：
Do, Kee Hun;Kim, Min Sung;Bae, Sun Sik
血管紧张素II（AngII）是影响血管收缩并对血管平滑肌细胞施加肥大作用的关键激素。在这里，我们发现，磷脂酰肌醇3-激酶依赖性钙动员在血管紧张素II诱导的血管收缩中起着关键作用。AngII刺激大鼠主动脉血管平滑肌细胞（RASMC）包埋的胶原凝胶快速诱导收缩。用磷脂酰肌醇3-激酶（PI 3 K）抑制剂（LY 294002）预处理可阻断AngII诱导的胶原凝胶收缩，而ERK抑制剂（PD 98059）则无效。血管紧张素II诱导的胶原凝胶收缩被EGTA或硝苯地平（一种L-型钙通道阻滞剂）的细胞外钙耗竭显著阻断。此外，AngII诱导的钙动员也被硝苯地平和EGTA阻断，而thapsigargin对细胞内钙库耗竭无效。最后，用LY 294002和硝苯地平预处理大鼠主动脉环显著减少AngII诱导的收缩。鉴于这些结果，我们认为，PI 3 K依赖性激活的L型钙通道可能参与血管紧张素II诱导的血管收缩。
Angiotensin II (AngII) is a crucial hormone that affects vasoconstriction and exerts hypertrophic effects on vascular smooth muscle cells. Here, we showed that phosphatidylinositol 3-kinase-dependent calcium mobilization plays pivotal roles in AngII-induced vascular constriction. Stimulation of rat aortic vascular smooth muscle cell (RASMC)-embedded collagen gel with AngII rapidly induced contraction. AngII-induced collagen gel contraction was blocked by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) whereas ERK inhibitor (PD98059) was not effective. AngII-induced collagen gel contraction was significantly blocked by extracellular calcium depletion by EGTA or by nifedipine which is an L-type calcium channel blocker. In addition, AngII-induced calcium mobilization was also blocked by nifedipine and EGTA, whereas intracellular calcium store-depletion by thapsigargin was not effective. Finally, pretreatment of rat aortic ring with LY294002 and nifedipine significantly reduced AngII-induced constriction. Given these results, we suggest that PI3K-dependent activation of L-type calcium channels might be involved in AngII-induced vascular constriction.