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

已知肾小球系膜细胞具有对血管紧张素II特异的受体，以响应血管紧张素II而吸引，从而有助于调节肾小球滤过率。近年来研究发现，肾小球系膜细胞能产生肾素，系膜细胞功能障碍可损害肾内肾素-血管紧张素系统的活性，从而引起糖尿病肾内血流动力学改变。为探讨糖尿病肾内肾素-血管紧张素系统的变化与血流动力学改变的关系，本实验检测了体外培养的肾小球系膜细胞和糖尿病大鼠肾脏中肾素和血管紧张素原信使RNA（mRNA）水平及血管紧张素转换酶（ACE）活性。提示系膜细胞仅作为肾素-血管紧张素系统的效应细胞发挥作用。糖尿病大鼠肾脏中的肾素和血管紧张素原的mRNA水平与对照组大鼠肾脏中的mRNA水平无差异。与此相反，糖尿病大鼠肾脏（外皮质和内皮质加外髓质）ACE活性均显著低于对照组，提示糖尿病肾内肾素-血管紧张素系统的主要变化是ACE活性降低，从而导致肾内血管紧张素II生成减少，导致糖尿病特征性小动脉血管舒张。

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.