The penetration into the glomerular basement membrane of anionic and cationic ferritin has been studied in rats made proteinuric by intraperitoneal administration of bovine serum albumin. In comparison with control animals anionic ferritin penetrated the glomerular basement membrane to a much greater extent in proteinuric rats. Some ferritin particles were observed in small invaginations of the epithelial cell membrane adjacent to the glomerular basement membrane and incorporated in pinocytotic vesicles within the epithelial cell cytoplasm. This was not seen in control animals. Cationic ferritin distribution in the glomerular basement membrane was similar in control and proteinuric rats suggesting that the increased anionic ferritin penetration observed occurs without any reduction in fixed anionic charge.
Female Wistar rats were made heavily proteinuric by daily intraperitoneal injections of bovine serum albumin over 5 days. The size and charge permeability characteristics of the glomerular filter in this condition were determined by studying the renal handling of poly-dispersed uncharged dextran over the range of molecular radii 2-6 nm (albumin 3.6 nm), and of endogenous rat serum albumin over the same clearance period. In proteinuric rats the clearance of rat serum albumin was significantly increased with a resultant reduction in the circulating levels of rat serum albumin. The clearance of uncharged dextran was not significantly different in proteinuric rats compared with control animals. There does not appear to be any size selective defect of the glomerular filtration barrier in this condition. This suggests that the observed increase in the clearance of the negatively charged endogenous albumin may be due to a reduction in the glomerular charge barrier.
SUMMARY1. Conscious rats received a saline infusion (5-8 ml. hr-') via a tail vein, for a 6 hr period. For the final 2 hr of this infusion period, prolactin (74 ,tg (100 g body wt.)-'. hr-1) was incorporated in the infusate. A control group of animals continued to receive saline alone.2. In the first hour of prolactin administration (in comparison with the control group), urine flow, sodium output and osmolal output were all significantly reduced (P < 0-02); there was also a reduction (P < 0-05) in renal plasma flow (p-aminohippurate clearance), but the filtration fraction did not alter. The changes in urinary excretion, and in renal haemodynamics, did not persist for the second hour of prolactin adminstration, but there was a sustained increase in body fluid volume.3. It is possible that altered renal haemodynamics are responsible for the reduced urinary water and solute excretion which occurs during acute prolactin administration.
In ketamine-anaesthetized rats, the infusion of 10 ml either isotonic (0.9%) or hypertonic (3.0%) saline over a 30-min period was associated with a decrease in the secretory activity of the anterior pituitary prolactin cells (assessed morphologically by electron microscopy), and a decrease in the serum prolactin concentration (determined by radioimmunoassay). The hypertonic saline infusion significantly (P less than 0.01) increased the serum osmolality whereas the isotonic infusion did not. The results indicated that prolactin release is reduced in response to volume expansion regardless of whether the fluid load is isotonic or hypertonic, and suggested that, in the rat, the hormone may play a role in volume regulation rather than osmoregulation.
Female Munich-Wistar rats were given intraperitoneal injections either of bovine serum albumin to induce proteinuria or of water as a control. Their kidneys were fixed in situ. An ultrastructural technique was used to demonstrate IgG antiperoxidase antibodies either injected from a heterologous species or autologous, induced by immunization with horseradish peroxidase. Photometry of electron micrographic negative was used to determine the distribution of antiperoxidase antibodies. In glomeruli of control animals IgG was present in the basement membrane. There were three sites at which the passage of IgG across the basement membrane was hindered: between blood plasma and the lamina rara interna, between the lamina densa and the lamina rara externa, and between the lamina rara externa and the urinary space. Glomeruli of proteinuric animals were variable in appearance, some showing little structural damage and others showing marked changes with loss of epithelial foot processes and accumulation of vacuoles and protein droplets in epithelial cells. Both types of glomeruli contained IgG in the urinary space. The distribution of IgG in the basement membrane of both types was similar. Compared with control animals there was less IgG in the basement membrane and IgG was distributed uniformly across the basement membrane. The proteinuria in hyperalbuminaemia (protein-overload) is associated with a diffuse change in the barrier function of the glomerular basement membrane to IgG which is, at least in the initial stages, not related to structural changes in glomerular epithelial cells.
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