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Effects of Arg‐Gly‐Asp Sequence Peptide and Hyperosmolarity on the Permeability of Interstitial Matrix and Fenestrated Endothelium in Joints
Author(s) -
POLI A.,
MASON R. M.,
LEVICK J. R.
Publication year - 2004
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680490476024
Subject(s) - evans blue , osmole , synovial fluid , osmotic concentration , saline , chemistry , interstitial fluid , synovial membrane , biophysics , anatomy , endocrinology , medicine , pathology , biology , biochemistry , osteoarthritis , inflammation , alternative medicine
Objectives: The aims were to assess the contribution of arg‐gly‐asp (RGD) mediated cell integrin–matrix bonds to interstitial hydraulic resistance and to fenestrated endothelial permeability in joints. Joint fluid is generated by filtration from fenestrated capillaries and drains through a fibronectin‐rich synovial intercellular matrix. The role of parenchymal cell–matrix bonding in determining tissue hydraulic resistance is unknown. Methods: The knee cavity of anesthetized rabbits was infused with saline or the competitive hexapeptide blocker GRGDTP, with or without added osmotic stress (600 mosm saline). Intra‐articular pressure P j , net trans‐synovial drainage rate s , and the permeation of Evans blue‐labeled albumin (EVA) from plasma into the joint cavity were measured. Results: GRGDTP increased the hydraulic conductance of the synovial drainage pathway, d s / dP j , by 71% ( p = .02, paired t test, n = 6 animals). Synovial plasma EVA clearance (control 7.1 ± 0.8 μL h −1 , mean ± SEM, n = 15) was unaffected by GRGDTP (7.0 ± 2.3 μL h −1 , n = 6) or hyperosmolarity (4.9 ± 1.5 μL h −1 , n = 8) but was increased by GRGDTP and hyperosmolarity together (15.9 ± 4.8 μL h −1 , n = 5) ( p = .01, ANOVA). Changes in dP j / dt evoked by GRGDTP plus hyperosmolarity, but neither alone, demonstrated increased microvascular filtration into the joint cavity ( p < .001, ANOVA), as did changes in fluid absorption from the infusion system at fixed P j . Conclusions: RGD‐mediated bonds between the parenchymal cells and interstitial polymers reduce the interstitial hydraulic conductance by 42%. This helps to retain the lubricating fluid inside a joint cavity. RGD‐mediated bonds also support the macromolecular barrier function of fenestrated endothelium, but in vivo this is evident only in stressed endothelium (cf. in vitro ).