Effect of the Cytoskeletal Fixation Agent Phalloidin on Transcapillary Albumin Transport and Interstitial Fluid Pressure in Anaphylaxis in the Wistar Rat

• Published in: Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2002-06, Vol.9 (3), p.197-205
• Main Authors: BRØNSTAD, AURORA, REITH, ALISON, BERG, ANSGAR, REED, ROLF K.
• Format: Article
• Language: English
• Subjects: connective tissue cells; cytoskeleton; dextran; edema; inflammation; interstitial fluid pressure (Pif); phalloidin
• ISSN: 1073-9688; 1549-8719
• DOI: 10.1038/sj.mn.7800134

ABSTRACT Objective: Interstitial fluid pressure (Pif) 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, Pif falls from −0.5 mm Hg to a value between −5 and −10 mm Hg. It is believed that Pif 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 Pif in response to a pretreatment with phalloidin, a reagent that fixes the actin filaments within the cell. Methods: Pif was measured in anesthetized female Wistar rats by using a micropuncture technique. The rats were pretreated with phalloidin followed by dextran. Albumin extavasation (Ealb) was measured as the extravascular space of 125I‐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 Pif 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 Pif, giving values of −0.6 ± 0.2 mm Hg (p < 0.05, compared to dextran). The Ealb 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. Conclusion: This study shows that pretreatment with phalloidin, before the administration of dextran, abolishes the lowering of Pif and edema formation, which is detected after i.v. injection of dextran alone.