Nonfasting Munich-Wistar Fromter rats were surgically prepared for in vivo imaging (n = 6). Rats were placed on the microscope stage with the exposed kidney placed in a cover slip-bottomed dish bathed in warm isotonic saline. Rats were then injected i.v. with rat serum albumin conjugated to Texas Red that was observed to enter capillary loops of superficial glomeruli, move into Bowman's space, bind to the proximal tubular cell brush border and reabsorbed across the apical membrane. Glomerular sieving coefficient (GSC) was calculated as the ratio of conjugated albumin within the glomerular capillary versus that in Bowman's space. Rats were again studied after 2 weeks of chronic ET-1 (2 pmol/kg/min; i.v. osmotic minipump).
Glomerular sieving coefficient was significantly increased in rats following chronic ET-1 infusion (0.025 ¡À 0.005 vs. 0.017 ¡À 0.003, p < 0.05). Mean fluorescence intensity for conjugated albumin within proximal tubules was increased by ET-1 infusion: 118.40 ¡À 6.34 vs. 74.27 ¡À 4.45 pixel intensity (p < 0.01).
These data provide in vivo evidence that ET-1 directly increases glomerular permeability to albumin and that albuminuria is prevented by increased PT albumin uptake in the rat.