Chronic endothelin-1 (ET-1) infusion in Sprague-Dawley rats increases glomerular permeability to albumin (Palb) as assessed in vitro independent of blood pressure with no observed albuminuria. In this study, we hypothesized that ET-1 increases glomerular albumin filtration with accompanied increase in albumin uptake via the proximal tubule (PT). Munich-Wistar rats were surgically prepared for in vivo imaging (n=3). Rats were placed on the microscope stage with the exposed kidney placed in a coverslip-bottomed dish bathed in warm isotonic saline. Rats were then injected i.v. with rat serum albumin conjugated to Texas Red (AT) and studied again after 2 wk of chronic ET-1 (2 pmol/kg/min; i.v. osmotic minipump). AT was observed to enter capillaries of superficial glomeruli, move into Bowman's space, bind to the PT cell brush border and reabsorbed across the apical membrane. Glomerular-sieving coefficient(GSC) was calculated as the ratio of AT within the glomerular capillaryvs. that in Bowman's space. GSC was significantly increased in rats following chronic ET-1 infusion (0.039 ± 0.001 vs. 0.028 ± 0.001, p<0.05). Mean fluorescence intensity for ATin PTs was increased by ET-1: 118 ± 6 vs. 76 ± 3 pixel intensity (p<0.05). These data provide in vivo evidence that ET-1 directly increases Palb and that albuminuria is prevented by increased PT albumin uptake in the rat (NIH P-30 O'Brien Center for Advanced Renal Microscopy).