Kinugawa K, Takahashi T, Kohmoto O, Yao A, Ikenouchi H, Serizawa T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Cardiovasc Res. 1995 Sep;30(3):419-31.
There remain some controversies about the effect of angiotensin II on intracellular Ca2+ concentration ([Ca2+]i) in cardiac myocytes. The aim of this study was to investigate different roles of intracellular Ca2+ in the responses to angiotensin II between cardiac myocytes and nonmyocytes.
Primary cultures of neonatal rat cardiac myocytes and nonmyocytes were prepared. [Ca2+]i was measured with indo-1. Cellular growth was assayed by [3H]thymidine uptake, RNA content, [3H]phenylalanine incorporation and protein content. Induction of immediate-early gene was examined by Northern blot analysis.
In myocytes, angiotensin II decreased [Ca2+]i transients, induced c-fos mRNA, and accelerated hypertrophy. These effects were completely suppressed by AT1 receptor blockade or protein kinase C inhibition. After chelation of extracellular Ca2+, angiotensin II caused no change in [Ca2+]i or no induction of c-fos in myocytes. Phorbol 12-myristate 13-acetate also decreased [Ca2+]i transients, caused c-fos induction, and provoked hypertrophy in myocytes. In nonmyocytes, angiotensin II increased [Ca2+]i transiently, induced c-fos mRNA and hypertrophy. These effects of angiotensin II were not fully abolished by protein kinase C inhibition. Extracellular Ca2+ chelation did not completely inhibit the effects of angiotensin II on [Ca2+]i or c-fos induction in nonmyocytes. Phorbol 12-myristate 13-acetate did not affect [Ca2+]i or cellular growth in nonmyocytes but did cause c-fos induction.
These results suggest that angiotensin II induces cellular hypertrophy and immediate-early genes through the activation of protein kinase C in myocytes, although angiotensin II decreases [Ca2+]i transients via this signaling pathway. Induction by angiotensin II of hypertrophy and immediate-early genes in nonmyocytes may be in part mediated by a transient increase in [Ca2+]i which acts synergistically with protein kinase C activation.
关于血管紧张素II对心肌细胞内钙离子浓度（[Ca2+]i）的影响仍存在一些争议。本研究的目的是探讨细胞内钙离子在心肌细胞和非心肌细胞对血管紧张素II反应中的不同作用。
制备新生大鼠心肌细胞和非心肌细胞的原代培养物。用indo-1测量[Ca2+]i。通过[3H]胸腺嘧啶核苷摄取、RNA含量、[3H]苯丙氨酸掺入和蛋白质含量来检测细胞生长。通过Northern印迹分析检测即刻早期基因的诱导情况。
在心肌细胞中，血管紧张素II降低[Ca2+]i瞬变，诱导c-fos mRNA表达，并加速肥大。这些作用被AT1受体阻断或蛋白激酶C抑制完全抑制。细胞外钙离子螯合后，血管紧张素II对心肌细胞的[Ca2+]i无影响或不诱导c-fos表达。佛波酯12-肉豆蔻酸酯13-乙酸盐也降低[Ca2+]i瞬变，诱导c-fos表达，并引起心肌细胞肥大。在非心肌细胞中，血管紧张素II短暂增加[Ca2+]i，诱导c-fos mRNA表达和肥大。蛋白激酶C抑制并未完全消除血管紧张素II的这些作用。细胞外钙离子螯合并未完全抑制血管紧张素II对非心肌细胞[Ca2+]i或c-fos诱导的作用。佛波酯12-肉豆蔻酸酯13-乙酸盐对非心肌细胞的[Ca2+]i或细胞生长无影响，但可诱导c-fos表达。
这些结果表明，血管紧张素II通过激活心肌细胞中的蛋白激酶C诱导细胞肥大和即刻早期基因，尽管血管紧张素II通过该信号通路降低[Ca2+]i瞬变。血管紧张素II在非心肌细胞中诱导肥大和即刻早期基因可能部分由[Ca2+]i的短暂增加介导，其与蛋白激酶C激活协同作用。
