Molecular Cell Biological Analysis on Renal Structure and Function

本研究的结果包括：1)与正常血压大鼠系膜细胞相比，自发性高血压大鼠(SHR)和Dahl盐敏感型高血压大鼠(DS)的系膜细胞没有增加前列腺素的产生以及细胞外氯浓度降低时钙信号和收缩的减弱；2)胰岛素样生长因子-I受体的激活减弱了正常系膜细胞的钙信号和收缩；3)IGF-I对SHR系膜细胞的钙信号和收缩没有调节作用，但在DS系膜细胞中存在；4)IGF-I对SHR的GFR没有影响，但它增加了正常血压大鼠的GFR；5)Na/H交换器-I仅存在于LLCPK-1细胞的基底外侧；6)β1受体的mRNA表达分析显示其在远端小管表达；7)氯电导存在于兔近端小管的基底外侧。此外，我们提出了我们的假设，即本研究项目中系膜细胞调节障碍是通过肾小球血流动力学改变包括肾小球反馈紊乱而导致高血压的发生。

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.