Effect of decreased perfusion pressure on glomerular permeability in the rat

In several models of glomerular injury and in studies with tracers that affect systemic or regional hemodynamics, renal perfusion rate and perfusion pressure are often markedly reduced. In order to distinguish the possible effect of these hemodynamic changes from changes in intrinsic properties of the glomerular filter, we investigated alterations in glomerular permeability in anaesthesized rats with acutely lowered perfusion pressure induced by ligation of the aorta to a mean arterial pressure (MAP) of approximately 55 mmHg. Control rats underwent similar surgery except for aorta constriction. Filtration properties were studied by determining the fractional clearance of three differently charged horseradish peroxidases, with a molecular radius of approximately 30 A and an isoelectric point of 4 (anionic), 7.6 (native), or 9 (cationic) (N = 4 per group). Glomerular filtration rate was determined by inulin clearance and renal plasma flow was determined by inulin extraction. In addition, the effect of lowering MAP on penetration of intravenously administered ferritin into the glomerular capillary wall was studied by electron microscopy and morphometric analysis. The results showed that glomerular filtration rate and renal plasma flow decreased proportionally upon lowering MAP. The fractional clearances of the three differently charged peroxidases were unchanged, indicating unaltered charge-selective barrier function of the glomerular filter. In the animals with reduced MAP, no significant differences were found in ferritin concentration in glomerular capillary lumina of superficial glomeruli as compared to control animals. Penetration of ferritin into the capillary wall was found to be proportional with the amount of ferritin in the lumen in both experimental (N = 5) and control animals (N = 4). In conclusion, a decrease in perfusion pressure causing a marked reduction of glomerular filtration rate and renal plasma flow, had no effect on the charge discriminative properties of the glomerular filter and on permeability to large protein molecules such as ferritin. Furthermore, this study shows that in order to assess glomerular permeability by ultrastructural tracer studies, it is necessary to relate the intramembranous and intraluminal concentration of a given tracer.