CV6209 INHIBITS AIRWAY WALT THICKENING AND AIRWAY HYPERRESPONSIVENESSTO HISTAMINE-INDUCED BY INTRAVENOUS ADMINISTRATION OF PLATELET-ACTIVATING-FACTOR IN GUINEA-PIGS

We studied the effect of intravenous administration of platelet-activa ting factor (PAF) on airway responsiveness to histamine and airway wal l thickening in guinea pigs, Guinea pigs were killed and the lungs wer e fixed in formalin. Slides from paraffin-embedded sections of the lun gs were stained and the airways that were cut in transverse section we re measured by tracing enlarged images using a digitizer, Moreover, ai rway resistance (Raw) was determined by a pulmonary mechanics analyzer and we calculated two indices, an index of airway wall thickening and one of airway hyperresponsiveness to histamine, from changes of basel ine-Raw and peak-Raw following intravenous administration of histamine before and after PAF administration, The infusion of 600 ng/kg PAF fo r 1 h induced an increase in the thickness of the airway wall in main bronchi demonstrable by histological examination. In analysis of airwa y function, the infusion of 600 ng/kg PAF for 1 h induced airway hyper responsiveness to histamine with airway wall thickening. The PAF antag onist CV6209, which was given intravenously 30 min prior to PAF admini stration, inhibited these effects of PAF in a dose-dependent manner, s uggesting PAF may induce airway wall thickening and airway hyperrespon siveness through PAF receptors in the airways.