Me. Koller et al., ALPHA-TRINOSITOL PREVENTS INCREASED NEGATIVITY OF INTERSTITIAL FLUID PRESSURE IN RAT SKIN AND TRACHEA INDUCED BY DEXTRAN ANAPHYLAXIS, European journal of pharmacology, 331(2-3), 1997, pp. 259-266
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 beta(1)-integrins, and m
ay therefore represent a novel principle for therapy of the phenomena
associated with acute inflammation. Increased negativity of interstiti
al 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 mu m)
connected to a servocontrolled counterpressure system. alpha-Trinosito
l (10 mg) was given before or after dextran. Circulatory arrest was in
duced 2 min after i.v. dextran to limit the increased capillary fluid
filtration associated with the anaphylactic reaction. This increased f
iltration will otherwise raise interstitial volume and thereby p(if) a
nd cause an underestimation of a potential increased negativity of p(i
f). 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 de
xtran) and -4.7 +/- 3.0 mmHg (P < 0.01 versus control and dextran), re
spectively. 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 p
rior to dextran the corresponding figures were -0.4 +/- 0.8 and -0.9 /- 11 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-trinos
itol prevented the increased negativity of p(if) induced by dextran an
aphylaxis when administered prior to as well as after dextran showing
that the alpha-trinositol also could influence an already started infl
ammatory reaction. (C) 1997 Elsevier Science B.V.