Effect of PGE1, PGI2, and PGF2α analogs on collagen gel compaction in vitro and interstitial pressure in vivo

Acute inflammation in skin is accompanied by increased negativity of interstitial fluid pressure (P-IF), 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 P-IF and mediate this response. The present study describes a novel effect of prostaglandin (PG) E-1 isopropyl ester, carbaprostacyclin (PGI(2) analog), and latanoprost (PGF(2 alpha) analog) on edema formation and P-IF in parallel with their action on the fibroblast-populated collagen gel contraction assay. The prostaglandins were injected subdermally in pentobarbital-anesthetized rats. P-IF 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 P-IF PGE(1) (0.91 mM) and carbaprostacyclin (1.28 mM) lowered P-IF 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 dosedependent manner. Edema formation was measured in separate experiments. PGE(1) and carbaprostacyclin significantly increased interstitial fluid volume (extravascular Cr-51-EDTA space) at concentrations as low as 0.1 and 1.1 mu M, respectively. Latanoprost had no effect on P-IF or edema formation. However, latanoprost reversed, in a dose-dependent manner, an increased negativity of P-IF accompanying the anaphylactic reaction to dextran. In the gel contraction assay with human diploid fibroblasts (AG 1518), a corresponding specificity was observed where PGE(1) 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 P-IF via loose connective tissue cells.