Regulation of renin and angiotensinogen gene expression in glomerular mesangial cells.

已知肾小球系膜细胞具有血管紧张素II的特异性受体，可在血管紧张素II的作用下进入，从而有助于调节肾小球滤过率。由于最近有报道称系膜细胞能够产生肾素，系膜细胞功能障碍可能会损害肾内肾素-血管紧张素系统的活性，从而导致糖尿病特有的肾内血流动力学改变。为探讨糖尿病大鼠肾内肾素-血管紧张素系统的变化与血流动力学改变的关系，检测了体外培养的糖尿病大鼠肾小球系膜细胞肾素和血管紧张素原信使RNA水平及血管紧张素转换酶(ACE)活性，但在不同条件下培养的肾小球系膜细胞均未检测到肾素和血管紧张素原信使RNA及ACE活性，提示系膜细胞只能作为肾素-血管紧张素系统的效应因子发挥作用。糖尿病大鼠肾脏肾素和血管紧张素原的信使RNA水平与对照组相比无明显差异。与上述结果相反，糖尿病大鼠肾脏(外皮质和内皮质+外髓质)的ACE活性明显低于对照组，提示糖尿病大鼠肾内肾素-血管紧张素系统的主要变化是ACE活性降低，这可能导致肾内血管紧张素II的生成减少，导致糖尿病特有的小动脉扩张。

Glomerular mesangial cells are known to have receptors specific to angiotensin II, to entract in response to angiotensin II and, thus, to contribute to the regulation of glomerular filtration rates. Since it has been recently reported that mesangial cells are able to produce renin, dysfunction of mesangial cells may impair the activity of intrarenal renin-angiotensin system and, thus, produce intrarenal hemodynamic alterations characteristic to diabetes. In order to evaluate the association of the changes in intrarenal renin- angiotensin system with hemodynamic alterations in diabetes, messenger RNA levels of renin and angioten- sinogen and angiotensin converting enzyme (ACE) activity in cultured mesangial cells and in kidneys of diabetic rats were examined.Neither messenger RNA of renin or angiotensinogen nor ACE activity was detected in glomerular mesangial cells cultured under various conditions, indicating that mesangial cells could function only as an effector of renin-angiotensin system. Messenger RNA levels of renin and angiotensinogen in kidneys of diabetic rats were not different from those in kidneys of control rats. In contrast to these results, ACE activity in kidneys (in both outer cortex and inner cortex plus outer medulla) of diabetic rats was significantly reduced compared with that of control rats.These results indicate that the main change in intrarenal renin-angiotensin system in diabetes is decrease in ACE activity, which could result in decrease in generation of intrarenal angiotensin II, leading to vasodilatation of arterioles characteristic to diabetes.