Effects of thromboxane synthase and cyclooxygenase inhibition on PAF-induced changes in lung function and arachidonic acid metabolism
| Autor: | Brian W. Christman, James R. Snapper, G. A. King, Peter L. Lefferts, D.S. Trochtenberg, Y.S. Hwang |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
Tetrahydronaphthalenes Thromboxane Pilot Projects Pulmonary compliance Biochemistry chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Platelet Activating Factor Lung Meclofenamic Acid Arachidonic Acid Sheep biology Platelet-activating factor Chemistry Imidazoles respiratory system Body Fluids Eicosanoid Enzyme inhibitor Prostaglandin-Endoperoxide Synthases biology.protein Respiratory Mechanics lipids (amino acids peptides and proteins) Cyclooxygenase Thromboxane-A synthase Lymph Thromboxane-A Synthase |
| Zdroj: | Prostaglandins. 44(6) |
| ISSN: | 0090-6980 |
| Popis: | PAF was administered as an intravenous bolus (0.1 μg/kg) to eight chronically instrumented awake sheep. The effects of pretreatment with an inhibitor of cyclooxygenase (meclofenamate) on PAF-induced changes in lung function were compared to those observed with a specific inhibitor of thromboxane synthase (DP1904). Each animal was studied four times in varied order: PAF alone, PAF + DP1904, PAF + meclofenamate, and DP1904 alone. Saline alone (control), DP1904 alone, and meclofenamate alone did not cause changes in any of the measured variables. DP1904 and meclofenamate significantly attenuated the PAF-induced fall in lung compliance, elevation in peak pulmonary artery pressure, and increased lung lymph flow. Both drugs abolished the PAF-induced increases in lung lymph thromboxane B 2 concentrations. Meclofenamate, but not DP1904, blocked the rise in lymph 6-keto-PGF 1α . Although meclofenamate blocked the rise in lymph PGE 2 , DP1904 resulted in levels 2.7 times higher than PAF alone. We conclude that: (1) inhibition of thromboxane synthase is as effective as inhibition of cyclooxygenase in attenuating PAF-induced changes in lung function, and (2) thromboxane synthase inhibition results in augmented production of PGE 2 following PAF administration in vivo . |
| Databáze: | OpenAIRE |
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