alpha-Trinositol prevents increased negativity of interstitial fluid pressure in rat skin and trachea induced by dextran anaphylaxis.
The new anti-inflammatory agent alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate), is suggested to act on the cellular adhesion receptor towards extracellular matrix components, the beta1-integrins, and may therefore represent a novel principle for therapy of the phenomena associated with acute inflammation. Increased negativity of interstitial fluid pressure (p(if)) is a major driving force for the rapid edema formation in trachea and skin associated with dextran anaphylaxis in the rat. We therefore used this experimental model to study the effect of alpha-trinositol in skin and trachea of pentobarbital anesthetized rats. p(if) was measured with sharpened glass capillaries (3-7 microm) connected to a servocontrolled counterpressure system. alpha-Trinositol (10 mg) was given before or after dextran. Circulatory arrest was induced 2 min after i.v. dextran to limit the increased capillary fluid filtration associated with the anaphylactic reaction. This increased filtration will otherwise raise interstitial volume and thereby p(if) and cause an underestimation of a potential increased negativity of p(if). In the trachea, p(if) was 0.0 +/- 1.0 mmHg (S.D.) and -1.4 +/- 0.5 mmHg in controls given saline vehicle and alpha-trinositol (P > 0.05), respectively, and fell to -8.5 +/- 2.7 mmHg after dextran (P < 0.01). alpha-Trinositol given 2 min prior to or after dextran resulted in p(if) of -1.7 +/- 1.2 mmHg (P > 0.05 versus control, P < 0.01 versus dextran) and -4.7 +/- 3.0 mmHg (P < 0.01 versus control and dextran), respectively. In skin, i.v. dextran caused p(if) to fall from -0.6 +/- 0.5 to -4.6 +/- 1.9 mmHg (P < 0.001). When alpha-trinositol was given prior to dextran the corresponding figures were -0.4 +/- 0.8 and -0.9 +/- 1.1 mmHg, respectively (P > 0.05). Subdermal administration of alpha-trinositol after i.v. dextran and circulatory arrest normalized p(if) in concentration of 100, 10 and partly at 1 mg/ml. Thus, alpha-trinositol prevented the increased negativity of p(if) induced by dextran anaphylaxis when administered prior to as well as after dextran showing that the alpha-trinositol also could influence an already started inflammatory reaction.
Koller
M E
ME
Department of Anesthesiology, University of Bergen, Norway.
Berg
A
A
Rodt
S A
SA
Westerberg
E
E
Reed
R K
RK
D000707:Anaphylaxis / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001826:Body Fluids / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D003911:Dextrans; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007275:Injections, Intravenous; D007295:Inositol Phosphates / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000473:pathology / Q000503:physiopathology; D014132:Trachea / Q000473:pathology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003911:Dextrans; D007295:Inositol Phosphates; D011189:Potassium Chloride; C059368:atrinositol