Lowering of interstitial fluid pressure after neurogenic inflammation is inhibited by mystixin-7 peptide

Abstract

Soft tissue injury is accompanied by lowering of interstitial fluid pressure (P(if)), plasma protein extravasation, and edema. Inflammation was produced by electrical stimulation (ES) of the vagus and the effects of the synthetic peptide mystixin-7 (p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH(2)) on P(if) were examined. Micropuncture measurement of P(if) in submucosa, without opening the trachea, was conducted on rats anesthetized with pentobarbital sodium (50 mg/kg) and euthanized with intravenous KCl. P(if) in control (intravenous saline) was -1.2 +/- 0.7 mmHg before ES and decreased to -4.7 +/- 1.0 mmHg (P < 0.01, n = 8) after ES. Mystixin-7 (10 and 20 microg/kg iv) blocked the fall in P(if) after ES (-1.1 +/- 0.3 and -0.8 +/- 0.2 mmHg, P < 0.01, n = 8 and n = 4). The 1 microg/kg dose was without effect. When trachea from animals pretreated with mystixin-7 (20 microg/kg iv) were soaked in phosphate-buffered saline (0.15 M, pH 7.4), the rate of fluid accumulation was significantly reduced. This study suggests that mystixin peptides, which have structural similarity to a fragment from laminin-alpha1 chain, may be useful tools for studying cell adhesion and factors that maintain the structural integrity of connective tissue after injury.