INHIBTORY EFFECTS OF TACHYKININ RECCEPTOR ANTAGONISTS ON LEUK0TKIENE C₄-INDUCED CARDIOVASCULAR RESPONSES IN GUINEA PIGS

This study is to determine whether sensory neuropeptides are involved in thecardiovascular effects of leukotriene C₄(LTC₄).LTC₄(0. 8 nmol·kg^-1,iv)caused hypotensiveresponse and increased Evans blue extravasation frOm the atria and ventricles in anaesthetized guineapigs.CP-96345(2.06umol·kg^-1,iv), a tachykinin NK-1 receptor antagonist,and SR-48968(1.66umol· kg^-1,iv), an NK-2 receptor antagonist,partially inhibited LTC₄-induced increase(46. 6%and 37. 5%, respectively)of dye extravasation from the atria of guinea pigs. COmbination of CP-96345 and SR-48968 markedly inhibited LTC₄-induced hypotension and increase of microvascularleakage in both atria and ventricles(58.1%and 54.1%, respectively),similar to the inhibition byONOI078(0. 06umol·kg^-1,iv),a specific leukotriene antagonist.These resuIts suggest that NK-1and NK-2 receptors may be involved in the hypotension and the inflammation of heart induced byLTC₄.