title: Effect of PGE1, PGI2, and PGF2 alpha analogs on collagen gel compaction in vitro and interstitial pressure in vivo.
abstract: 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.
authors.affiliation: Department of Physiology, University of Bergen, Norway. Ansgar@pki.uib.no
authors.forename: A
authors.initials: A
authors.lastname: Berg
authors.forename: A K
authors.initials: AK
authors.lastname: Ekwall
authors.forename: K
authors.initials: K
authors.lastname: Rubin
authors.forename: J
authors.initials: J
authors.lastname: Stjernschantz
authors.forename: R K
authors.initials: RK
authors.lastname: Reed
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D003094:Collagen / Q000737:chemistry*; D004487:Edema / Q000209:etiology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005782:Gels; D007700:Kinetics; D000077338:Latanoprost; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011312:Pressure; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005782:Gels; D010982:Platelet-Derived Growth Factor; D011461:Prostaglandins F, Synthetic; D011465:Prostaglandins, Synthetic; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C026678:carboprostacyclin; D000077338:Latanoprost; D003094:Collagen; D011464:Epoprostenol; D000527:Alprostadil