Molecular Cell Biological Analysis on Renal Structure and Function

本研究项目的研究结果包括：1)与正常血压大鼠系膜细胞相比，自发性高血压大鼠（SHR）和达尔盐敏感型高血压大鼠（DS）系膜细胞不存在前列腺素分泌增强、Ca信号衰减和细胞外Cl浓度降低时收缩的现象；2)胰岛素样生长因子(IGF)- 1受体激活可减弱正常系膜细胞Ca信号和收缩；3) SHR系膜细胞中不存在igf - 1对Ca信号和收缩的调节，而DS系膜细胞中存在；4)输注igf - 1对SHR大鼠GFR无影响，而正常对照组GFR升高；5) Na/H交换器- i仅存在于LLCPK-1细胞的基底外侧；6) β 1受体mRNA表达分析显示其在远端小管中表达；7)兔近端小管基底外侧存在Cl传导。此外，我们提出了我们的假设，即在本研究项目中，系膜细胞调节的紊乱是通过改变肾小球血流动力学（包括干扰小管肾小球反馈）导致高血压的发生的基础。

The findings of the present research project include ; 1) in contrast to mesangial cells from normotensive rat, enhanced prostaglandin production and attenuation of Ca signal and contraction when extracellular Cl concentration was decreased were absent in mesangial cells of spontaneously hypertensive rat (SHR) and Dahl salt sensitive hypertensive rat (DS) ; 2) normal mesangial cell Ca signal and contraction was attenuated by insulin like growth factor (IGF)-I receptor activation ; 3) modulation of mesangial cell Ca signal and contraction by IGF-I was absent in SHR mesangial cells but present in DS mesangial cells ; 4) IGF-I infusion had no effect on GFR in SHR while it increased GFR in normotensive control rat ; 5) Na/H exchanger-I was present only on the basolateral side of LLCPK-1 cells ; 6) analysis of beta1 receptor mRNA expression revealed its expression in distal tubule ; and 7) Cl conductance was present on the basolateral side of rabbit proximal tubule.Furthermore, we advanced our hypothesis that disturbance of mesangial cell regulation in this research project underlies the development of hypertension via altered glomerular hemodynamics including disturbed tubuloglomerular feedback.