Abstract |
We have used three selective inhibitors of arachidonic acid metabolism in order to investigate the role of lipoxygenase metabolites in the pathogenesis of traumatic shock (LD90). The following inhibitors were used: CGS-5391B (2.5 mg/kg), a cyclooxygenase and lipoxygenase inhibitor, CGS-5677 (2.0 mg/kg), a selective lipoxygenase inhibitor, and U-60,257 (0.3 mg/kg), a putative inhibitor of glutathione-s-transferase. These inhibitors did not alter arterial blood pressure or heart rate when given to sham shock rats. The traumatic shock model was characterized by a 4.5-fold increase in plasma cathepsin D activity, a 4-fold increase in plasma myocardial depressant factor ( MDF) activity, and a mean survival time of 1.5 +/- 0.2 h. Only the dual inhibitor significantly blunted the accumulation of cathepsin D in the plasma (7.5 +/- 0.8 vs 11.3 +/- 0.8 U/ml, p less than 0.01). However, all three inhibitors significantly suppressed plasma MDF accumulation by 50-60%: CGS-5391B, CGS-5677, and U-60,257 (p less than 0.01). Moreover, these three agents significantly improved survival time in traumatic shock. The increased survival time and reduced MDF activity afforded by these inhibitors suggest a significant role for lipoxygenase metabolites, particularly LTC4 and LTD4, in the pathogenesis of traumatic shock.
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Authors | C E Hock, L Loprest, A M Lefer |
Journal | Prostaglandins
(Prostaglandins)
Vol. 28
Issue 4
Pg. 557-71
(Oct 1984)
ISSN: 0090-6980 [Print] United States |
PMID | 6441186
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Benzothiepins
- Cyclooxygenase Inhibitors
- Lipoxygenase Inhibitors
- Organic Chemicals
- CGS 5677
- Epoprostenol
- Arachidonate Lipoxygenases
- Lipoxygenase
- piriprost
- enolicam
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Topics |
- Animals
- Arachidonate Lipoxygenases
- Benzothiepins
(therapeutic use)
- Blood Pressure
- Cyclooxygenase Inhibitors
- Epoprostenol
(therapeutic use)
- Heart
(drug effects)
- Lipoxygenase
(therapeutic use)
- Lipoxygenase Inhibitors
- Male
- Models, Biological
- Organic Chemicals
- Rats
- Rats, Inbred Strains
- Shock
(drug therapy, mortality)
- Time Factors
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