Glomerular Endothelial Cells in Uranyl Nitrate-induced Acute Renal Failure in Rats

Abstract

A B S T R A C T 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 (i±SEM) per 5 cm2 from the scanning electron micrographs (x30,000) was 107+10, 103+9, and 101+11 at 2, 7, and 17h 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 (i± 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 lowu-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% ofthe 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.

Endothelial characteristics of glomerular capillaries in normal, mercuric chloride-induced, and gentamicin-induced acute renal failure in the rat.

“…The high dose of gentamicin used in this study (40 mg/kg b.i.d. for [8][9] d) was reflected in the severe reduction in creatinine clearance 102±39 ,l/min) and elevation of serum creatinine (5.0±0.6 mg/dl). At the time of killing, extensive necrosis was present in the proximal convolutions (79±3%) and in the proximal pars recta (43±10%) (24).…”

“…A (19), by gentamicin (20), and by ischemia (2). It has been proposed that the reduction in endothelial fenestral size and density underlie the decrease in ultrafiltration coefficient (Kf) measured in these different models of acute renal failure (4)(5)(6)(7)(8)(9). The relationship between these ultrastructural lesions and changes in ultrafiltration is unclear, and concern has been expressed that tissue fixation conditions and photographic field selection may influence the assessment of endothelial changes by scanning electron microscopy (21).…”

“…1, 2, 2 inset). Additionally, the large numbers of pores measured in this study (4,680 pores per group of animals studied, Table I) should have helped eliminate bias in pore selection.…”

“…It has been suggested that these changes underlie the decrease in glomerular filtration rate and altered glomerular capillary hemodynamics measured in various experimental models of acute renal failure. We have thoroughly quantitated the surface characteristics of glomerular capillaries in control rats and in rats with either mercuric chloride-induced acute renal failure (2 mg/kg body wt) evaluated at 6 and 24 h after administration of the nephrotoxin or with gentamicin (G)'-induced acute renal failure evaluated after [8][9] d of 40 mg/kg body wt twice a day. Despite reductions in glomerular filtration rate in the experimental groups, no significant differences were observed between control (C) and any experimental group with respect to percent areas occupied by fenestrated endothelium (C = 53.6±2.7%; 6 h HgCl2 = 50.9±1.9%; 24 h HgCl2 = 53.9±5.7%; G = 56.7±2.4%), by cytoplasmic ridges (C = 31.2±1.5%; 6 h HgCl2 = 29.8±1.9%; 24 h HgCl2 = 30.6±3.1%; G = 26.5±1.5%), nonfenestrated endothelium (C = 15.5±4.0%; 6 h HgCl2 = 19.3±2.0%; 24 h HgCl2 = 15.6±4.3%; G = 16.9±2.3%), in the individual pore area expressed in square nanometers (C = 1,494±75; 6 h HgCl2 = 1,326±48; 24 h HgCl2 = 1,559±130; G = 1,340±101), or in the percentage of total pore area within fenestrated areas that were measured (C = 12.8±0.8%; 6 h HgCl2 = 11.2+0.7%; 24 h HgCI2 = 10.9±0.8%; G = 10.9±0.7%).…”

“…This new methodology has allowed for a more thorough evaluation of the glomerular endothelium in a variety of experimental conditions. Using this technique, significant changes in glomerular capillary pore size and pore density have been reported in ischemic (2), glycerol-induced (3), aminoglycoside-induced (4)(5)(6)(7)(8), and nephrotoxic (9) models of experimental acute renal failure, as well as in cases of acute renal failure in man (10). Similar changes have been demonstrated in rats with alloxan-induced diabetes (11), in aminonucleoside-induced nephrosis (12), and in rats with spontaneously developing hypertension (13).…”