Su Jin-Zi, Fukuda Noboru, Jin Xue-Qing, Lai Yi-Mu, Suzuki Ryo, Tahira Yoshiko, Takagi Hiroto, Ikeda Yukihiro, Kanmatsuse Katsuo, Miyazaki Hitoshi
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hypertension. 2002 Dec;40(6):853-8. doi: 10.1161/01.hyp.0000042096.17141.b1.
We recently reported that overexpression of the angiotensin II type 2 (AT2) receptor downregulates the AT1a receptor through the bradykinin/NO pathway in a ligand-independent manner in vascular smooth muscle cells (VSMCs). In the present study, we investigated the effect of AT2 receptor overexpression on the expression of the AT1a receptor and transforming growth factor-beta (TGF-beta) receptor subtypes in VSMCs from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Transfection of the AT2 receptor gene downregulated expression of the AT1a receptor in VSMCs from WKY, but did not affect expression of the AT1a receptor in VSMCs from SHR. Transfection of the AT2 receptor abolished DNA synthesis in response to angiotensin II in VSMCs from WKY; in VSMCs from SHR, basal DNA synthesis was suppressed, but DNA synthesis in response to Ang II was not altered. The NO substrate L-arginine augmented downregulation of the AT1a receptor in VSMCs from WKY, whereas it did not affect expression of the AT1a receptor in VSMCs from SHR. In response to AT2 receptor transfection, expression of TGF-beta type I receptor mRNA was suppressed significantly in VSMCs from WKY, whereas expression of TGF-beta type I receptor was not altered in VSMCs from SHR. These results suggest that the AT2 receptor downregulates AT1a and TGF-beta type I receptors in normal VSMCs, but not in SHR-derived VSMCs. The lack of downregulation of the AT1a receptor may contribute, in part, to the exaggerated growth of VSMCs from SHR.
我们最近报道，血管平滑肌细胞（VSMCs）中血管紧张素II 2型（AT2）受体的过表达通过缓激肽/一氧化氮（NO）途径以配体非依赖方式下调AT1a受体。在本研究中，我们研究了AT2受体过表达对自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）VSMCs中AT1a受体和转化生长因子-β（TGF-β）受体亚型表达的影响。AT2受体基因转染下调了WKY的VSMCs中AT1a受体的表达，但不影响SHR的VSMCs中AT1a受体的表达。AT2受体转染消除了WKY的VSMCs中对血管紧张素II的DNA合成反应；在SHR的VSMCs中，基础DNA合成受到抑制，但对血管紧张素II的DNA合成未改变。NO底物L-精氨酸增强了WKY的VSMCs中AT1a受体的下调，而不影响SHR的VSMCs中AT1a受体的表达。响应AT2受体转染，WKY的VSMCs中TGF-β I型受体mRNA的表达显著受到抑制，而SHR的VSMCs中TGF-β I型受体的表达未改变。这些结果表明，AT2受体在正常VSMCs中下调AT1a和TGF-β I型受体，但在SHR来源的VSMCs中则不然。AT1a受体下调的缺乏可能部分导致SHR的VSMCs过度生长。
