VASOCONSTRICTION AND BRONCHOCONSTRICTION INDUCED BY 2,5-DI-(TERT-BUTYL)1,4-BENZOHYDROQUINONE, AN ENDOPLASMIC RETICULAR CA2+-ATPASE INHIBITOR, IN ISOLATED AND PERFUSED RAT LUNG

The microsomal Ca2+-ATPase inhibitor 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) induced bronchoconstriction and vasoconstriction in the isolated perfused and ventilated rat lung. Thes effects were accompanied by increased levels of thromboxane and prostacyclin in the effluent perfusate. The effect of tBuBHQ was inhibited by L-655,240, a thromboxane receptor antagonist, indicating thromboxane-A2-mediated bronchoconstriction and vasoconstriction. Accordingly, the cyclooxygenase inhibitor indomethacin largely blocked the effects of tBuBHQ. The involvement of a phospholipase in the generation of thromboxane A2 (TXA2) was supported by dibucaine protection on tBuBHQ effects. The results from this study indicate that tBuBHQ, probably by inhibiting the microsomal Ca2+-ATPase, can trigger the arachidonic acid cascade leading to the formation of TXA2, which in turn causes bronchoconstriction and vasoconstriction in rat lung

SULFUR DIOXIDE-INDUCED BRONCHOCONSTRICTION IN THE ISOLATED PERFUSED AND VENTILATED GUINEA-PIG LUNG

SO2 exposure (50-500 ppm) of isolated, perfused and ventilated guinea pig lungs, via the air passages, caused a concentration-related reduction in dynamic compliance and conductance. No changes in pulmonary perfusion flow was noted at any SO2 concentration. Formed sulfite was detected in lung lavage fluid as well as in the perfusate. Pretreatment of the lungs with a low concentration of SO2 (10 ppm) for 30 min protected against bronchoconstriction by a high concentration of SO2 (250 ppm). A similar protective effect was noted by pretreatment with sodium sulfite (3 mM) in the lung perfusate