IN-VIVO INHIBITION OF TRANSCELLULAR WATER CHANNELS (AQUAPORIN-1) DURING ACUTE PERITONEAL-DIALYSIS IN RATS

During peritoneal dialysis (PD), a major portion of the osmotically in duced water transport to the peritoneum can be predicted to occur thro ugh endothelial water-selective channels. Aquaporin-1 (AQP-1) has rece ntly been recognized as the molecular correlate to such channels. Aqua porins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tis sue fixation, used to protect the tissues from HgCl2 damage. Dianeal ( 3.86%) was employed as dialysis fluid, I-I25-albumin as an intraperito neal volume market; and Cr-51-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immuno cytochemistry and immunoelectron microscopy revealed abundant AQP-1 la beling in capillary endothelium in peritoneal tissues, representing si tes for HgCl2 inhibition of water transport. HgCl2 treatment reduced w ater flow and inhibited the sieving of Na+ without causing any untowar d changes in microvascular permeability, compared with that of fixed c ontrol rats, in which the peritoneal cavity was exposed to tissue Fixa tion alone. In fixed control rats, the mean intraperitoneal volume (IP V) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 mi in GO min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rat s the dialysate Nai concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibi tion of water flow through aquaporins. The observed HgCl2 inhibition o f transcellular water channels strongly indicates a critical role of a quaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis .