Inhibitory effects of tachykinin receptor antagonists on leukotriene C4-induced cardiovascular responses in guinea pigs

This study is to determine whether sensory neuropeptides are involved in the cardiovascular effects of leukotriene C4 (LTC4). LTC4 (0.8 nmol.kg-1, i.v.) caused hypotensive response and increased Evans blue extravasation from the atria and ventricles in anaesthetized guinea pigs. CP-96345 (2.06 mumol.kg-1, i.v.), a tachykinin NK-1 receptor antagonist, and SR-48968 (1.66 mumol.kg-1, i.v.), 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 microvascular leakage in both atria and ventricles (58.1% and 54.1%, respectively), similar to the inhibition by ONO-1078 (0.06 mumol.kg-1, i.v.), a specific leukotriene antagonist. These results suggest that NK-1 and NK-2 receptors may be involved in the hypotension and the inflammation of heart induced by LTC4.