BRADYKININ-INDUCED PLASMA EXUDATION IN GUINEA-PIG AIRWAYS - INVOLVEMENT OF PLATELET-ACTIVATING-FACTOR

1. We studied the effect of bradykinin on plasma exudation in the airways of the anaesthetized guinea-pig in vivo. Tissue content of extravasated Evans blue dye was used as an index of protein exudation in the larynx, trachea, main bronchi and intrapulmonary airways (i.p.a.). 2. Bradykinin increased the content of Evans blue in all tissues studied in a dose-related manner. The response was greatest in the main bronchi and i.p.a., less in the trachea and least in the larynx. A dose of 47 nmol kg-1 was the lowest tested which caused significant (P < 0.001) plasma exudation with increases in leakage above control values of 256% in the larynx, 405% in the trachea, 394% in the main bronchi and 485% in intrapulmonary airways. 3. Leakage was significantly (P < 0.05) increased above control values by 1 min after bradykinin (47 nmol kg-1) in the main bronchi and intrapulmonary airways and was maximal in all airways 5 min after bradykinin. Although reduced by 15 min, the tissue content of dye was still significantly (P < 0.05) increased 2 h after bradykinin. 4. The prolonged tissue dye retention was due to a later phase of slow and maintained exudation preventing full clearance of dye after the initial response. 5. The initial phase of leakage was partially attenuated by the platelet activating factor (PAF) receptor antagonists WEB 2086 or BN 52021, by indomethacin or by inhibiting sensory nerve activation by opioid anaesthesia: it was not affected by mepyramine and cimetidine nor by the sulphidopeptide leukotriene receptor antagonists FPL 55712 or ICI 198,615. Adrenoceptor blockade of the anti-leakage effects of endogenously-released catecholamines significantly (P < 0.05) enhanced leakage. 6. The later phase of plasma leakage was completely inhibited by the PAF antagonists. 7. We conclude that, in guinea-pig airways in vivo, the initial phase of bradykinin-induced plasma exudation is mediated in part by PAF, sensory nerves and prostaglandins, whereas the later, prolonged phase of leakage is mediated exclusively by PAF. If bradykinin is generated in asthma, its potent and prolonged effects on plasma leakage may contribute significantly to airway oedema and may be involved in the development of bronchial hyperresponsiveness.