Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure

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Abstract
A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. The maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g l-1) at different flow rates and hence arterial pressures (PA). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant PA of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 +/- 2.9 ml min-1 100 g-1) were similar in the two kidneys at equal PA and remained constant throughout the experiment. The ratio of albumin clearance over GFR (theta) was initially around 0.4% at constant PA and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of PA from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10-15 mmHg and in a two-fold increase of theta when measured at an identical PA of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated PGC per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria.