Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx.
OBJECTIVE
In this study, we wished to determine whether angiopoietin-1 (Ang1) modified the permeability coefficients of non-inflamed, intact continuous, and fenestrated microvessels in vivo and to elucidate the underlying cellular mechanisms.


RESULTS
Permeability coefficients were measured using the Landis-Michel technique (in frog and rat mesenteric microvessels) and an oncopressive permeability technique (in glomeruli). Ang1 decreased water permeability (L(P): hydraulic conductivity) in continuous and fenestrated microvessels and increased the retention of albumin (sigma: reflection coefficient) in continuous microvessels. Endothelial glycocalyx is common to these anatomically distinct microvascular beds, and contributes to the magnitude of both L(P) and sigma. Ang1 treatment increased the depth of endothelial glycocalyx in intact microvessels and increased the content of glycosaminoglycan of cultured microvascular endothelial cell supernatant. Ang1 also prevented the pronase-induced increase in L(P) (attributable to selective removal of endothelial glycocalyx by pronase) by restoration of glycocalyx at the endothelial cell surface. The reduction in permeability was inhibited by a cell transport inhibitor, Brefeldin.


CONCLUSIONS
Ang1 modifies basal microvessel permeability coefficients, in keeping with previous reports demonstrating reduced solute flux in inflamed vessels. Anatomical, biochemical, and physiological evidence indicates that modification of endothelial glycocalyx is a novel mechanism of action of Ang1 that contributes to these effects.
Salmon
Andrew H J
AH
Department of Physiology and Pharmacology, Preclinical Veterinary School, Microvascular Research Laboratories, Bristol Heart Institute, University of Bristol, Southwell Street, Bristol, UK.
Neal
Christopher R
CR
Sage
Leslie M
LM
Glass
Catherine A
CA
Harper
Steven J
SJ
Bates
David O
DO
D000418:Albumins / Q000378:metabolism; D042683:Angiopoietin-1 / Q000502:physiology*; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D019276:Glycocalyx / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply; D055806:Microvessels / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D011402:Pronase / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011896:Rana temporaria; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014867:Water / Q000378:metabolism
D000418:Albumins; D042683:Angiopoietin-1; D006025:Glycosaminoglycans; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D014867:Water; D020126:Brefeldin A; D011402:Pronase