Platelet-lung in vivo interactions: an artifact of a multi-purpose model?

The simultaneous evaluation of platelet behaviour in vivo and of the accompanying bronchoconstriction in the guinea pig is described. Arachidonic acid induces bronchoconstriction, accompanied by, but independent from, thrombocytopenia, whereas collagen induces bronchoconstriction also accompanied by, but dependent from, thrombocytopenia. In both cases bronchoconstriction is due to cyclo-oxygenase metabolites of arachidonic acid. Use of potential inhibitors of thromboxane synthetase failed to reveal which of prostaglandin endoperoxides or thromboxane A2 is responsible for aspirin-inhibitive bronchoconstriction and thrombocytopenia. In contrast to PGE1 prostacyclin failed to interfere with bronchoconstriction by serotonin or by arachidonic acid, even though thrombocytopenia by the latter was suppressed. Bronchoconstriction by collagen, in contrast, was inhibited by nanogram doses of prostacyclin, confirming platelet-dependency. The combined bronchoconstriction/thrombocytopenia test in guinea pigs can discriminate sites of action of anti-inflammatory drugs, of agents which block specific platelet and/or bronchial receptors, which stimulate the cyclic AMP system, or generically which interfere with the mechanisms of bronchoconstriction and of thrombocytopenia.