[The effect of elastase on aminonucleoside nephrosis--on renal vascular system].

This study was performed to investigated the relationship between cross sectional areas of glomerular arterioles and glomerular volume in rats with puromycin aminonucleoside (PAN)-induced nephrosis, which is an experimental model of glomerular sclerosis. We also evaluated the effect of an anti-arteriosclerotic agent, elastase on these parameters. Six-week-old male Sprague-Dawley rats were divided into 3 groups; control, PAN-treated (70 mg/kg i.p.), or PAN+elastase-treated (5 mg/kg/day i. m.) group. After 12 weeks of experimental period, microvascular cast of the kidney was prepared, and the cross sectional areas of afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary glomeruli with minor abnormalities, the efferent arteriole was narrower in PAN-treated rats than in the control rats and the elastase-treatment partially corrected it (control 55.7, PAN 35.9, PAN+elastase 43.7 x 10 microns 2). On the other hand, the cross sectional area of afferent arteriole was not different among the 3 groups. In glomeruli showing sclerosis, the cross sectional area of efferent arteriole correlated positively with the glomerular volume. There results suggest that constriction of the efferent arterioles contributes to the development of glomerular sclerosis in PAN-induced nephrosis. In addition, elastase possibly inhibits this process and thereby protect glomeruli from sclerosis.

Mesangial anionic sites are decreased in human focal glomerular sclerosis.

We studied the mesangial anionic sites in two patients with focal glomerular sclerosis (FGS), using polyethyleneimine as a cationic probe. The mesangial negative charge in the FGS patients was less than that in three control patients. The decrease in negative charge in FGS concerned the central, paramesangial, as well as the subendothelial region of the mesangium; the decrease was most pronounced in the central region. It is proposed that loss of mesangial negative charge may have pathogenic significance in FGS.

Morphometric analysis of the glomerular capillary area--a comparison of minimal change nephrotic syndrome, focal glomerular sclerosis, and pre-eclampsia.

A morphometric analysis was performed to compare the capillary area in non-sclerotic glomeruli in focal glomerular sclerosis (FGS), pre-eclampsia with focal sclerotic change of the glomeruli, and minimal change nephrotic syndrome (MCNS). The mean and standard deviation of the capillary area was greater in FGS than in pre-eclampsia and MCNS. Tubulo-interstitial lesions, such as tubular atrophy, interstitial fibrosis, and lymphocytic infiltration, were more severe in FGS than in pre-eclampsia. The presence of tubulo-interstitial changes including tubular atrophy and interstitial fibrosis with lymphocytic infiltration is thought to be an important prognostic factor in pre-eclampsia as well as in FGS. Unequal dilatation of the glomerular capillaries in non-sclerotic glomeruli may be harmful to the glomeruli and may lead to the development of glomerular sclerosis.

Focal segmental glomerular hyalinosis and/or sclerosis in rats with congenital unilateral hydronephrosis.

Focal segmental glomerular hyalinosis and/or sclerosis (FSHS) was observed in five Wistar-Imamichi rats with congenital unilateral hydronephrosis (CUH rats). Marked proteinuria (164.9 +/- 138.4 mg/day) was observed in the CUH rats. Immunoperoxidase staining for IgM, C3 and IgG was positive in the glomeruli, showing in a focal, segmental pattern that corresponded to the areas of FSHS seen by light microscopy. These glomerular findings were extremely similar to those of human focal glomerular sclerosis (FGS). FSHS was found to be common to both the hydronephrotic kidney and the contralateral kidney without hydronephrosis. Morphometry revealed that the glomerular area of the juxtamedullary glomeruli was greater than that of superficial glomeruli in control rats (11,037 micron2 vs. 6,847 microns2). On the other hand, glomerular hypertrophy was observed in non-sclerotic glomeruli of CUH rats (superficial glomeruli; 12,477-16,123 microns2, juxtamedullary glomeruli; 14,635-18,418 microns2). Also, a decreased in the number of glomeruli within the range 1.8-4.1 per unit area (1 mm2) was seen in CUH rats compared with control rats (mean 4.4). These results suggest that the increased rate of development of FSHS is based on hyperfiltration in the remaining functional nephrons.

Changes of anionic sites in the mesangium with aging in rats: a comparison of the immersion and intravenous PEI methods.

We investigated the changes in anionic sites of the mesangial matrix related to aging in rats, employing polyethyleneimine (PEI) as a cationic probe. We compared the numbers of anionic sites detected by the immersion method and by the intravenous administration of PEI. Analysis of the mean numbers of PEI particles per 0.1 micron2 in the mesangial matrix revealed a significant decrease related to aging. Our results suggested that there was no significant difference in efficacy between the immersion and intravenous methods. Loss of negative charge of the mesangial matrix is believed to promote mesangial dysfunction and the entrapment of macromolecular substances, and so to play an important role in the onset of glomerular sclerosis.

[Pathomorphological studies on arterial cushion. 2. Aminonucleoside nephrotic rat].

The present study is an attempt to solve the problem of pathogenesis of focal glomerular sclerosis (FGS), especially in juxtamedullary cortex, we were investigated by measurement of luminal diameters of afferent arterioles (Aff), efferent arterioles (Eff) of numerous glomeruli, arterial cushion (AC), afferent arterioles (AC-aff) at a region of branching arteries from the interlobular arteries, using scanning electron micrographs of methyl methacrylate casts of intrarenal arteries of aminonucleoside nephrotic rats. As regards luminal diameters, Eff were nearly equal Aff in minor glomerular abnormalities (Minor). Nevertheless Eff of glomeruli with segmental sclerosis (FSHS) were smaller than Aff (t-test). AC with FSHS were smaller than ones of Minor, statistically (t-test). The results of these examination, the cushion may be important factor for the regulation of blood flow in sclerotic glomeruli.