Chua B H, Chua C C, Diglio C A, Siu B B
Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201.
Biochim Biophys Acta. 1993 Aug 18;1178(2):201-6. doi: 10.1016/0167-4889(93)90010-m.
In a series of experiments carried out in cultured endothelial cells derived from rat hearts (RHE), angiotensin II (AII) is shown to stimulate preproendothelin-1 mRNA in a dose- and time-dependent manner. The induction of preproendothelin-1 mRNA is rapid, reaching a maximal level 1 h after the addition of AII (1 x 10(-8) M). The mRNA levels decline rapidly to basal levels in 4 h. The addition of Losartan (Dup 753; 1 x 10(-6) M), an AII receptor (type I) antagonist, blocks the AII effect. Calphostin C, a potent protein kinase C inhibitor, is able to abolish this effect of AII suggesting that the induction of preproendothelin-1 mRNA is mediated by a protein kinase C-dependent pathway. Since endothelial cells line the inner surface of the myocardium and blood vessels and sense the rise of AII associated with renovascular hypertension at the endothelial surface, these data suggest that endothelin which is produced by RHE cells in response to AII could be an important mediator which may play a role in modulating gene expression in AII-mediated cardiac hypertrophy.
在一系列对源自大鼠心脏的培养内皮细胞（RHE）进行的实验中，血管紧张素II（AII）被证明以剂量和时间依赖性方式刺激前内皮素-1 mRNA。前内皮素-1 mRNA的诱导迅速，在添加AII（1×10⁻⁸ M）后1小时达到最大水平。mRNA水平在4小时内迅速下降至基础水平。添加AII受体（I型）拮抗剂氯沙坦（Dup 753；1×10⁻⁶ M）可阻断AII的作用。强效蛋白激酶C抑制剂钙泊三醇C能够消除AII的这种作用，表明前内皮素-1 mRNA的诱导是由蛋白激酶C依赖性途径介导的。由于内皮细胞排列在心肌和血管的内表面，并在内皮表面感知与肾血管性高血压相关的AII升高，这些数据表明，RHE细胞响应AII产生的内皮素可能是一种重要的介质，可能在调节AII介导的心脏肥大中的基因表达中发挥作用。
