Effects of Arg-Gly-Asp sequence peptide and hyperosmolarity on the permeability of interstitial matrix and fenestrated endothelium in joints.
OBJECTIVE
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 Pj, 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, ds/dPj, by 71% (p =.02, paired t test, n = 6 animals). Synovial plasma EVA clearance (control 7.1 +/- 0.8 microL h-1, mean +/- SEM, n = 15) was unaffected by GRGDTP (7.0 +/- 2.3 microL h(-1), n = 6) or hyperosmolarity (4.9 +/- 1.5 microL h(-1), n = 8) but was increased by GRGDTP and hyperosmolarity together (15.9 +/- 4.8 microL h(-1), n = 5) (p =.01, ANOVA). Changes in dPj/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 Pj.


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).
Poli
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Department of Physiology, St George's Hospital Medical School, London, UK.
Mason
R M
RM
Levick
J R
JR
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D004396:Coloring Agents / Q000493:pharmacokinetics; D004727:Endothelium / Q000187:drug effects* / Q000502:physiology; D005070:Evans Blue / Q000493:pharmacokinetics; D005109:Extracellular Matrix / Q000187:drug effects* / Q000502:physiology; D006982:Hypertonic Solutions / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects*; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009994:Osmolar Concentration; D010539:Permeability; D011312:Pressure; D011817:Rabbits; D000077331:Ringer's Solution; D013582:Synovial Fluid / Q000502:physiology
D000418:Albumins; D004396:Coloring Agents; D006982:Hypertonic Solutions; D007552:Isotonic Solutions; D009842:Oligopeptides; C080493:fibronectin attachment peptide; D005070:Evans Blue; C047981:arginyl-glycyl-aspartic acid; D000077331:Ringer's Solution