This project is designed to examine the mechanisms whereby glomerular filtration rate is regulated in a variety of acute and chronic physiologic states. Nephron filtration rate (sngfr) is determined by the product of the mean effective filtration pressure (EFP) and the glomerular permeability coefficient (L subp A). The effective filtration pressure is determined by a blance of hydrostatic forces (glomerular capillary - P sub G minus Bowman's space - P sub t hydrostatic pressure) and oncotic forces generated by capillary protein concentration pi. These determinants of ultrafiltration force are measured directly with a servo nulling device in Munich-Wistar rats and with microprotein measurements of aortic and peritubular capillary blood samples. Studies have been completed which demonstrate that if systemic oncotic pressure (pi sub A) is elevated by hyperoncotic albumin infusion, sngfr rises 70 percent. This increase is the result primarily of an increase in L sub p A. This value can be accurately calculated because low protein rats were utilized which did not achieve filtration equilibrium. Studies are in progress to determine the mechanism whereby mannitol increases filtration rate in both hydropenic rats and animals with acute myohemoglobinuric renal failure. Also, the mechanism of reduction of sngfr in this form of acute renal failure is being determined. We plan to evaluate the effects of ureteral obstruction, angiotensin infusion and a series of nephron loss models such as chronic nephritis and unilateral nephrectomy to determine the mechanism whereby sngfr changes.