Regulation of Glomerular Ultrafiltration by Glomerular Epithelial Cells

肾小球滤过是由肾小球超滤压力和超滤系数定义的。前者受肾小球传入和传出动脉收缩或松弛的调节，但超滤在肾小球中的调控机制尚不清楚。心钠素(ANP)是一种促进利尿和利钠的激素，它通过增加超滤系数和随后的肾小球滤过率，并通过抑制集合管对钠的重吸收来促进利尿和利钠。为阐明肾小球细胞在肾小球超滤过程中的调节作用，采用核糖核酸酶保护实验和原位杂交技术，将利钠肽受体的mRNA定位于肾脏。核糖核酸酶保护试验和原位杂交显示肾小球上皮细胞有A型和C型ANP受体亚型的mRNA。由于A型受体而不是C型受体在细胞质区域具有鸟苷酸环化酶结构域，因此ANP被认为通过与A型受体结合来兴奋肾小球上皮细胞，并介导超滤系数的增加。体内注射特异性抗体对肾小球上皮细胞造成的免疫损伤扭曲了肾小球滤过功能，如肾小球超滤系数。形态计量学分析显示，免疫损伤后肾小球cpithclial cclls体积增加，其他变化不明显。反过来，当肾小球系膜细胞被体内注射另一种抗体破坏时，超滤系数降低。这些结果表明，肾小球上皮细胞通过改变超滤系数在调节肾小球滤过中起重要作用，而超滤系数也可能受系膜细胞的调节。

Glomerular filtration is defined by glomerular ultrafiltration pressure and ultrafiltration coefficicnt. The former has been shown to be regulated by constriction or relaxation of the glomerular afferent and efferent arteries, however how the ultrafiltration is controled in the glomerulus has not been clarified yet. Atrial natriuretic peptide (ANP) is a hormone which facilitates diuresis and natriuresis by increasing the ultrafiltration coefficient and subsequently the glomerular filtration rate and by suppressing sodium reabsorption from collecting ducts. To elucidate glomerular cells which play a role on regulation of glomerular ultrafiltration, mRNA for natriuretic peptide receptors was localized in the kidney by ribonucleasc protection assay and in situ hybridization. Ribonuclease protection assay and in situ hybridization showed that the glomerular epithelial cells have mRNA for type A and type C ANP reccptor subtypes. Since type A receptors but not type C receptors have guanylate cyclase domain in the cytoplasmic region, ANP is predicted to excite the glomerular epithelial cells through binding to the type A receptors and to mediate the increase of ultrafiltration coefficient.The immunological injury of the glomerular epithelial cells by an in vivo administration of a specific antibody in rats distorted the glomerular filtration function such as glomcrular ultrafiltration coefficient. Morphometric analysis revealed no alterations except an increase in the volume of glomerular cpithclial cclls after the immune injury of these cells. In turn, the ultrafiltration coeffieient decreased when mesangial cells were damaged by in vivo administration of another antibody against these cells. These results indicate that the glomerular cpithclial cells play an important role in the regulation of glomerular filtration through changing ultrafiltration coefficient which might be also regulated by mesangial cells as well.