Effect of the cytoskeletal fixation agent phalloidin on transcapillary albumin transport and interstitial fluid pressure in anaphylaxis in the wistar rat.
OBJECTIVE
Interstitial fluid pressure (P(if)) plays an important role in controlling interstitial fluid volume. In the early phase of rapid edema formation, such as in dextran-induced anaphylaxis in the Wistar rat, P(if) falls from -0.5 mm Hg to a value between -5 and -10 mm Hg. It is believed that P(if) is controlled by the interaction between connective tissue cells and the extracellular matrix. This hypothesis was tested by studying dextran-induced edema formation and the subsequent changes in P(if) in response to a pretreatment with phalloidin, a reagent that fixes the actin filaments within the cell.


METHODS
P(if) was measured in anesthetized female Wistar rats by using a micropuncture technique. The rats were pretreated with phalloidin followed by dextran. Albumin extavasation (E(alb)) was measured as the extravascular space of (125)I-labeled human serum albumin (HSA) after 25 minutes. Total tissue water (TTW) was calculated as the difference between wet weight and dry weight divided by dry weight. Localization of phalloidin was determined histologically by using rhodamine-labeled phalloidin.


RESULTS
Control P(if) values of -0.3 +/- 0.6 mm Hg dropped to -3.1 +/- 0.8 mm Hg after dextran treatment (p < 0.05). Pretreatment with phalloidin completely abolished this decrease in P(if), giving values of -0.6 +/- 0.2 mm Hg (p < 0.05, compared to dextran). The E(alb) in control rats of 0.02 +/- 0.02 mL/g DW increased to 1.35 +/- 0.43 mL/g DW after dextran treatment. Pretreatment with phalloidin before dextran treatment lowered the dextran value to 0.59 +/- 0.32 mL/g DW.


CONCLUSIONS
This study shows that pretreatment with phalloidin, before the administration of dextran, abolishes the lowering of P(if) and edema formation, which is detected after i.v. injection of dextran alone.
Brønstad
Aurora
A
Department of Physiology, University of Bergen, Bergen, Norway. aurora.bronstad@pki.uib.no
Reith
Alison
A
Berg
Ansgar
A
Reed
Rolf K
RK
D000707:Anaphylaxis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002196:Capillaries / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects*; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005404:Fixatives / Q000494:pharmacology*; D006801:Humans; D010590:Phalloidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*
D005404:Fixatives; D012709:Serum Albumin; D010590:Phalloidine