Effect of the cytoskeletal fixation agent phalloidin on transcapillary albumin transport and interstitial fluid pressure following subdermal prostaglandin E1 administration in the rat.
OBJECTIVE
Lowering of interstitial fluid pressure (Pif) facilitates fluid filtration across the capillary membrane and oedema formation in acute inflammation. The cellular mechanism behind this lowering of Pif involves beta1-integrins mediating contact between dermal cells and the extracellular matrix fibres, and also the cell cytoskeleton as disruption of actin filaments using cytochalasin-D induced a lowering of Pif and oedema formation. Fixation of actin with phalloidin attenuates oedema formation and abolishes lowering of Pif in anaphylaxis in the rat. The objective of this study was to determine whether phalloidin modifies lowering of Pif and albumin extravasation in rat skin also after prostaglandin E1 (PGE1).


METHODS
Pif was measured using micropipettes connected to a servo-controlled counterpressure system. Microvascular permeability was estimated as the albumin extravasation (Ealb) using radiolabelled human serum albumin.


RESULTS
Subdermal injection of PGE1 (0.85 mg mL-1) lowered Pif from -0.8 +/- 0.8 mmHg (SD) in control to -3.5 +/- 0.9 mmHg (P < 0.05) within 30 min. Pre-treatment with phalloidin (500 microg kg-1) before PGE1 resulted in Pif of -1.7 +/- 1.0 mmHg (P < 0.05 compared with PGE1). Ealb after subdermal saline was 0.07 +/- 0.04 mL g-1 DW and increased to 0.32 +/- 0.32 mL g-1 DW with PGE1 (P < 0.05) but was unaffected by pre-treatment with phalloidin given before PGE1 0.32 +/- 0.35 mL g-1 DW (P > 0.05 compared with PGE1 alone).


CONCLUSIONS
These results are consistent with the concept that the cytoskeleton actin filaments participate in control of Pif.
Brønstad
A
A
Department of Physiology, University of Bergen, Bergen, Norway.
Reed
R K
RK
Berg
A
A
D000418:Albumins / Q000493:pharmacokinetics*; D000527:Alprostadil / Q000008:administration & dosage*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D004487:Edema / Q000503:physiopathology; D045604:Extracellular Fluid / Q000187:drug effects*; D005260:Female; D005404:Fixatives / Q000494:pharmacology*; D007262:Infusions, Intravenous; D010590:Phalloidine / Q000494:pharmacology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects
D000418:Albumins; D005404:Fixatives; D010590:Phalloidine; D000527:Alprostadil