Hydrogen peroxide-induced broncho- and vasoconstriction in the isolated perfused and ventilated guinea pig lung.
The effect of hydrogen peroxide on perfusion flow, airway conductance (Gaw) and dynamic compliance (Cdyn of isolated perfused and ventilated guinea pig lungs was investigated. Hydrogen peroxide (50 microM in the perfusion buffer) induced a decrease in Gaw and Cdyn and perfusion flow during 5 min. of exposure. Hydrogen peroxide also caused an increase in the levels of thromboxane in the perfusate of the lung. The constrictor effects as well as the formation of thromboxane were inhibited by the cyclooxygenase inhibitor ibuprofen (50 microM). The thromboxane/prostaglandin endoperoxide receptor antagonist L-670,596 (1 microM) abolished the effects of hydrogen peroxide on perfusion flow, Gaw and Cdyn, but did not affect the formation of thromboxane. The thromboxane-synthetase inhibitor carboxyheptylimidazole (100 microM) reduced both the hydrogen peroxide-induced formation of thromboxane and vaso- and bronchoconstriction, suggesting a predominant role for thromboxane A2 versus prostaglandin H2 in these effects. A role for platelet-activating factor in mediating the effect of hydrogen peroxide could not be supported, as the platelet-activating factor receptor antagonist WEB 2086 (10 microM) did not affect hydrogen peroxide induced vaso- and brochoconstriction. The results of this study show that hydrogen peroxide induces thromboxane A2 mediated vaso- and bronchoconstriction in the isolated perfused and ventilated guinea pig lung. Platelet-activating factor does not appear to play a significant role in the hydrogen peroxide-induced vaso- and bronchoconstriction. Our results also suggest that the perfused guinea pig lung is more sensitive to hydrogen peroxide than the perfused rat lung.
Department of Toxicology and Environmental Health, Karolinska Institutet, Stockholm, Sweden.
G
G
Bannenberg
M
M
Kimland
A
A
Ryrfeldt
P
P
Moldeus
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects*
D002227:Carbazoles; D010972:Platelet Activating Factor; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C055662:prostaglandin endoperoxide receptor; C061299:L 670596; D013928:Thromboxane A2; D006861:Hydrogen Peroxide