Chatterjee P K, Weerackody R P, Mistry S K, Hawksworth G M, McLay J S
Department of Medicine & Therapeutics, University of Aberdeen, Scotland, United Kingdom.
Kidney Int. 1997 Sep;52(3):699-705. doi: 10.1038/ki.1997.385.
The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10(-10) M, 10(-8) M, 10(-6) M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proximal tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a significant early increase in [3H]thymidine uptake by 19% and 56% (P < 0.01), respectively, and a later increase in total protein content by 30% (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD 123319, indicating that the responses are mediated via the AT1 receptor and dependent upon the inhibition of adenylate cyclase.
肾近端小管细胞肥大是对多种刺激的一种适应性反应，可能与肾脏疾病的进展有关。单独或与其他生长因子联合作用的血管紧张素II已被证实参与了这一过程。本研究的目的是确定血管紧张素II和血管紧张素受体亚型在人肾近端小管细胞DNA合成和蛋白质合成中的作用。将人肾近端小管细胞原代培养物与血管紧张素II（10^(-10)M、10^(-8)M、10^(-6)M）单独或与氯沙坦、PD123319或8-溴-cAMP联合孵育24至120小时。用血管紧张素II（10^(-10)M、10^(-8)M）孵育人近端小管细胞，分别使[3H]胸苷摄取量在早期显著增加19%和56%（P<0.01），后期总蛋白含量增加30%（P<0.01）。血管紧张素II对DNA和蛋白质合成的作用被8-溴-cAMP和氯沙坦抑制，但未被PD 123319抑制，这表明这些反应是通过AT1受体介导的，并且依赖于腺苷酸环化酶的抑制。
