Role of angiotensin II-induced renal functional changes in mesangial deposition of exogenous ferritin in rats.

The relationship between acute angiotensin II (AII)-induced functional changes of the kidney and mesangial localization of macromolecules was investigated in rats utilizing native horse spleen ferritin as an exogenous tracer. One group of rats received a 30-minute infusion of a pressor dose of AII. Ten minutes before sacrifice they were injected with a single intravenous dose of ferritin. In the other group the injection of ferritin was followed by an 80-minute infusion of AII. Serial measurements of systolic blood pressure (BP), inulin clearance (CIN), p-aminohippuric acid (PAH) clearance (CPAH), filtration fraction (FF), and excretion of albumin (UAlb V) and ferritin (UFe V) were obtained. Although AII-treated rats showed significant increases of BP, FF, UAlb V and UFe V over controls, they were not different from controls with respect to plasma ferritin concentrations, renal delivery of ferritin, CPAH, and CIN. Semiquantitative evaluation of renal tissue by immunofluorescence and electron microscopy revealed that at 10 minutes no differences in the early and mild deposition of ferritin in the mesangium were appreciable. In contrast, at 80 minutes, AII-treated rats had markedly enhanced mesangial localization of ferritin when compared with controls. In the animals infused with AII for 80 minutes, the amount of glomerular ferritin deposition correlated strongly with UAlb V and UFe V. Combining the results of both, AII and controls at 80 minutes, these correlations were still present, in addition to weaker yet significant correlations of glomerular ferritin with BP and absolute changes of FF during the treatment period. The results show that, over a time interval of 80 minutes, AII augments the mesangial accumulation of ferritin in the presence of normal tracer delivery to the kidney. The enhanced mesangial localization of ferritin is observed under circumstances where overall increases in glomerular capillary permeability to albumin and ferritin are present. Although the precise mechanisms underlying these effects are not identified, AII-induced changes of glomerular microcirculatory forces and permeability properties of the glomerular capillary appear to be involved.