Pharmacological modulation of the endotoxin-induced increase in plasminogen activator inhibitor activity in rats
Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. Both the cyclooxygenase inhibitors acetylsalicylic acid and indomethacin enhanced PAI-1 induction. The combined cyclooxygenase-lipoxygenase inhibitor, BW755C, dose-dependently inhibited induction. Since five other lipoxygenase inhibitors, a phospholipase inhibitor, an inhibitor of leukotriene formation and dexamethasone had no effect on the endotoxin-induced increase in PAI-1 synthesis, the effect of BW755C could not be ascribed to its known pharmacological properties. In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or NG-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. Heparin and hirudin had no effect either. Overall, the data showed that the induction of PAI-1 synthesis by endotoxin in vivo can be up- and down-regulated pharmacologically, but the mechanisms involved remain elusive.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1992 |
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| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
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| Enthalten in: |
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis - 3(1992), 5 vom: 02. Okt., Seite 575-81 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Emeis, J J [VerfasserIn] |
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| Anmerkungen: |
Date Completed 06.01.1993 Date Revised 11.09.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM012606464 |
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| 100 | 1 | |a Emeis, J J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacological modulation of the endotoxin-induced increase in plasminogen activator inhibitor activity in rats |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 06.01.1993 | ||
| 500 | |a Date Revised 11.09.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. Both the cyclooxygenase inhibitors acetylsalicylic acid and indomethacin enhanced PAI-1 induction. The combined cyclooxygenase-lipoxygenase inhibitor, BW755C, dose-dependently inhibited induction. Since five other lipoxygenase inhibitors, a phospholipase inhibitor, an inhibitor of leukotriene formation and dexamethasone had no effect on the endotoxin-induced increase in PAI-1 synthesis, the effect of BW755C could not be ascribed to its known pharmacological properties. In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or NG-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. Heparin and hirudin had no effect either. Overall, the data showed that the induction of PAI-1 synthesis by endotoxin in vivo can be up- and down-regulated pharmacologically, but the mechanisms involved remain elusive | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Plasminogen Activator Inhibitor 1 |2 NLM | |
| 650 | 7 | |a 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine |2 NLM | |
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| 650 | 7 | |a Tissue Plasminogen Activator |2 NLM | |
| 650 | 7 | |a EC 3.4.21.68 |2 NLM | |
| 650 | 7 | |a Aspirin |2 NLM | |
| 650 | 7 | |a R16CO5Y76E |2 NLM | |
| 650 | 7 | |a 1-Methyl-3-isobutylxanthine |2 NLM | |
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| 650 | 7 | |a Indomethacin |2 NLM | |
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| 700 | 1 | |a Van den Hoogen, C M |e verfasserin |4 aut | |
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