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Am J Physiol Heart Circ Physiol 274: H663-H671, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 2, H663-H671, February 1998

Effect of PGE1, PGI2, and PGF2alpha analogs on collagen gel compaction in vitro and interstitial pressure in vivo

Ansgar Berg1, Anna-Karin Hultgård Ekwall2, Kristofer Rubin2, Johan Stjernschantz3, and Rolf K. Reed1

1 Department of Physiology, University of Bergen, N-5009 Bergen, Norway; 2 Department of Medical and Physiological Chemistry, University of Uppsala, S-75123 Uppsala; and 3 Pharmacia and Upjohn Company, S-75182 Uppsala, Sweden

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 (PGF2alpha 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 µM, 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.

acute inflammation; edema; loose connective tissue; latanoprost


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