In uranyl nitrate (UN)-induced acute renal failure (ARF) glomerular ultrafiltration coefficient (Kf) decreases because of unknown reasons. Since transport of water across the glomerular capillary wall occurs predominantly extracellularly through the endothelial fenestrae (EF), a reduction in the diameter and/or the density of EF can reduce the extracellular filtration area and the glomerular Kf. To examine this possibility, ARF was induced in rats by intravenous administration of UN in low (15 mg/kg) and high doses (25 mg/kg). Fenestral density (¯x±SEM) per 5 cm2 from the scanning electron micrographs (×30,000) was 107±10, 103±9, and 101±11 at 2, 7, and 17 h after the intravenous administration of bicarbonate saline to the control rats. In the low-dose UN group the EF density was 91±2, 52±8, and 45±11 at 2, 7, and 17 h after the injection, whereas for the high-dose group at corresponding time intervals the EF density was 95±3, 54±9, and 44±10. Fenestral diameters, in Angstrom units (¯x±SEM), were 751±53, 765±43, and 764±37 at 2, 7, and 17 h after the injection of bicarbonate saline to control rats. At corresponding intervals after the administration of UN, the fenestral diameters were 501±61, 472±28, and 438±98 for the low-dose group and 525±43, 470±39, and 440±56 for the high-dose group. 2, 7, and 17 h after the injection of UN, fenestral area of the low-dose group decreased to 52.1, 30.1, and 24.6% of the controls, whereas in the high-dose group, the fenestral area declined to 54.3, 30.2, and 23.6% of the controls. Administration of UN (15 mg/kg) to sodium-loaded rats did not alter renal function or endothelial cell morphology. It is suggested that in UN-induced ARF the morphological alterations in endothelial cells reduce the Kf of glomerular capillaries by reducing the filtration area.
P. S. Avasthi, A. P. Evan, D. Hay