Acute
inflammation in skin is accompanied by increased negativity of interstitial fluid pressure (PIF), which will increase capillary fluid filtration and thereby potentiate
edema formation. A series of studies indicates that the connective tissue cells in rat dermis are involved in the control of PIF and mediate this response. The present study describes a novel effect of
prostaglandin (PG) E1 isopropyl
ester,
carbaprostacyclin (PGI2 analog), and
latanoprost (
PGF2 alpha analog) on
edema formation and PIF in parallel with their action on the fibroblast-populated
collagen gel contraction assay. The
prostaglandins were injected subdermally in
pentobarbital-anesthetized rats. PIF was measured with a servo-controlled counterpressure system after circulatory arrest had been induced with saturated
potassium chloride. Circulatory arrest was induced to limit
edema formation that would raise interstitial fluid volume and thereby attenuate a possible increased negativity of PIF.
PGE1 (0.91 mM) and
carbaprostacyclin (1.28 mM) lowered PIF from a control value of -0.8 +/- 0.4 mmHg to -3.0 +/- 0.4 (P < 0.01) and -3.7 +/- 0.9 (P < 0.01) mmHg, respectively, within 45 min in a dose-dependent manner.
Edema formation was measured in separate experiments.
PGE1 and
carbaprostacyclin significantly increased interstitial fluid volume (extravascular 51Cr-
EDTA space) at concentrations as low as 0.1 and 1.1 microM, respectively.
Latanoprost had no effect on PIF or
edema formation. However,
latanoprost reversed, in a dose-dependent manner, an increased negativity of PIF accompanying the
anaphylactic reaction to
dextran. In the gel contraction assay with human diploid fibroblasts (AG 1518), a corresponding specificity was observed where
PGE1 and
carbaprostacyclin effectively inhibited gel contraction although
latanoprost had no effect. Thus the present data demonstrate a novel effect of
prostaglandins and provide further evidence for active modulation of PIF via loose connective tissue cells.