diamide and Pulmonary-Edema

Hydrogen peroxide (H2O2), arachidonic acid (AA), and U-44069, a thromboxane analogue, all induced vaso- and bronchoconstriction in the isolated perfused rat lung. The role of protein sulfhydryl modifications in these processes was investigated. The thiol oxidizing agent diamide inhibited both vaso- and bronchoconstriction induced by H2O2, AA, or U-44069. Diamide had only a marginal effect on glutathione and protein thiol levels and no effect on lung mechanics. The diamide inhibition was reversible, and H2O2-induced vaso- and bronchoconstriction was almost maximal after 10 min of perfusion with buffer. The recovery was more rapid if dithiothreitol, a thiol reducing agent, was used in the buffer. H2O2- and AA-induced vaso- and bronchoconstriction is caused by thromboxane release. Diamide did not influence H2O2- or AA-dependent thromboxane formation, indicating that neither AA release nor AA metabolism to thromboxane is sensitive to thiol oxidation. Thus our results indicate that the site of diamide-induced thiol oxidation is the thromboxane receptor or its signal transduction.

Topics: Animals; Arachidonic Acid; Bradykinin; Bronchoconstriction; Diamide; Dithiothreitol; Hydrogen Peroxide; In Vitro Techniques; Indoles; Lung Compliance; Male; Perfusion; Pulmonary Circulation; Pulmonary Edema; Rats; Rats, Inbred Strains; Serotonin; Sulfhydryl Compounds; Sulfhydryl Reagents; Thromboxane B2; Thromboxanes; Vasoconstriction