CELL BIOLOGY OF GLOMERULAR ULTRAFILTRATION

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The ability to regulate glomerular filtration rate is essential for the normal functioning of kidneys. In recent years, it has become evident that significant alterations in the permeability of the glomerular wall and/or surface area available for ultrafiltration (i.e. the ultrafiltration coefficient) can occur in response to a wide variety of important hormones, nephrotoxic compounds, and other altered physiological states. At present, the glomerular cells and morphological changes which are responsible for these alterations in the ultrafiltration coefficient are very speculative or unknown. In the proposed investigations, in vitro and in vivo studies are designed to carefully evaluate the morphological responses of glomerular epithelial podocytes, the glomerular endothelium, and the glomerular mesothelial cells in situations which alter the ultrafiltration coefficient in Munich-Wistar rats. Particular attention will be paid to the roles that cytoplasmic contractile elements, cytoskeletal elements, calcium ions, and prostaglandins play in affecting ultrastructural changes in these cells. Together, it is believed that the above studies will provide important insights into the roles played by the different cell types which make up the kidney glomerulus in regulating flow of filtrate across the glomerular wall, the cell biological parameters which underlie ultrafiltration coefficient related morphological changes in these cells, and will help define the mechanisms of action of many important compounds and conditions.