Abstract |
Phorbol myristate acetate (PMA) activates neutrophils and causes acute lung injury. We determined the effect of ONO-5046, a specific neutrophil elastase inhibitor, on the increase in microvascular permeability induced by PMA in isolated dog lung perfused with autologous blood at a constant perfusion flow. The vascular permeability was assessed by the capillary filtration coefficient (Kf, c) and the solvent-drag reflection coefficient (sigma f). PMA (13.3 micrograms) increased vascular permeability, as evidenced by an increase in Kf, c from 0.18 +/- 0.02 to 0.92 +/- 0.14 mL/min/cmH2O/100 g and a decrease in sigma f to 0.35 +/- 0.01 as compared to control values of 0.69 +/- 0.06. The PMA-induced changes in Kf, c and sigma f were dose-dependently attenuated by pretreatment with ONO-5046 (2-20 mg). We conclude that ONO-5046 can effectively attenuate the PMA-induced injury in the isolated blood-perfused dog lungs.
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Authors | H G Wang, T Shibamoto, T Miyahara, H Haniu, S Tanaka, K Fujimoto, T Honda, K Kubo, S Koyama |
Journal | Experimental lung research
(Exp Lung Res)
1999 Jan-Feb
Vol. 25
Issue 1
Pg. 55-67
ISSN: 0190-2148 [Print] England |
PMID | 10027079
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Serine Proteinase Inhibitors
- Sulfonamides
- Vasodilator Agents
- Papaverine
- sivelestat
- Leukocyte Elastase
- Tetradecanoylphorbol Acetate
- Glycine
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Topics |
- Animals
- Capillary Permeability
(drug effects)
- Dogs
- Female
- Glycine
(analogs & derivatives, pharmacology)
- In Vitro Techniques
- Leukocyte Elastase
(antagonists & inhibitors)
- Lung
(blood supply, drug effects, enzymology)
- Lung Diseases
(chemically induced, enzymology)
- Male
- Papaverine
(pharmacology)
- Perfusion
- Serine Proteinase Inhibitors
(pharmacology)
- Substrate Specificity
- Sulfonamides
(pharmacology)
- Tetradecanoylphorbol Acetate
(toxicity)
- Vasodilator Agents
(pharmacology)
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