Transvascular passage of macromolecules into the peritoneal cavity of normo- and hypothermic rats in vivo: active or passive transport?
During the last decades there has been a debate regarding whether transvascular protein transport is an active (transcytosis) or a passive (porous) process. To separate cooling-sensitive transcytosis from passive transport processes between blood and peritoneal fluid, we induced hypothermia in rats in vivo, reducing their body temperature to 19 degrees C. Control rats were kept at 37 degrees C. Either human albumin, or IgG, or IgM, or LDL, radiolabeled with (125)I, was given intra-arterially together with (51)Cr-EDTA. During tracer administration, a 2-hour peritoneal dialysis dwell was performed. Clearance of the tracers to dialysate, and the permeability-surface area coefficient (PS) for (51)Cr-EDTA and glucose were assessed. During cooling, mean arterial blood pressure (MAP) was reduced to 40% of control and plasma viscosity increased by 48.5%, while peritoneal blood flow was reduced to 10%. At 19 degrees C, clearance of albumin to dialysate fell from 9.30 +/- 1.62 (SEM) to 3.13 +/- 0.28 microl/min (p < 0.05), clearance of IgG from 6.33 +/- 0.42 to 2.54 +/- 0.12 microl/min (p < 0.05), clearance of IgM from 3.65 +/- 0.33 to 1.10 +/- 0.12 microl/min (p < 0.05), and clearance of LDL from 3.54 +/- 0.20 to 0.73 +/- 0.06 microl/min (p < 0.05). The fall in PS for (51)Cr-EDTA was from 0.320 +/- 0.01 to 0.075 +/- 0.003 ml/min (p < 0.05), and that for glucose from 0.438 +/- 0.02 to 0.105 +/- 0.01 ml/min (p < 0.05). Tissue cooling reduced large solute transport largely in proportion to the cooling-induced reductions of MAP (to 40%), and the concomitant increase in viscosity (to 67%), i.e. to approximately 20-30% (0.40 x 0.67) of control, though LDL clearance was reduced further. The fall in small solute PS, in excess of the viscosity effect, mirrored the fall in peritoneal blood flow occurring during hypothermia. In conclusion, the good correlation of predicted to calculated changes suggests that the overall transendothelial macromolecular passage in vivo occurs passively, and not due to active processes.
Rosengren
Bert-Inge
BI
Department of Nephrology and Department of Physiological Sciences, Lund University, Lund, Sweden. Bert-Inge.Rosengren@mphy.lu.se
Carlsson
Ola
O
Venturoli
Daniele
D
al Rayyes
Osama
O
Rippe
Bengt
B
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology*; D001794:Blood Pressure; D002199:Capillary Permeability / Q000502:physiology; D021941:Caveolae / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D006339:Heart Rate; D007035:Hypothermia / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D008970:Molecular Weight; D010529:Peritoneal Cavity / Q000502:physiology*; D010530:Peritoneal Dialysis; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D000418:Albumins; D008078:Cholesterol, LDL; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D046911:Macromolecular Substances