Reversal of leukotriene D4- and leukotriene E4-induced airway constriction in the guinea pig.

Conscious Hartley guinea pigs were challenged with LTD4 or LTE4 aerosols. When dynamic compliance (Cdyn) decreased to 50% of its baseline value, the challenge aerosols were stopped and treatment aerosols of salbutamol, the LTD4/E4 antagonist LY171883 Na, atropine, or sodium chloride (control) were begun. After 5 min of continuous exposure to the treatment aerosol, each animal was killed and excised lung gas volume (ELGV) was measured. Salbutamol was equally effective in reversing LTD4- and LTE4-induced Cdyn changes. Aerosolized LY171883 Na was effective against both agonists, but was about threefold more potent against LTE4. In contrast, atropine was very effective in reversing LTD4-induced Cdyn changes, but produced minimal reversal when LTE4 was the challenge agent. Pulmonary gas trapping results supported these observations; ELGV values were closely correlated with 5-min Cdyn measurements for both LTD4 (r = -0.817) and LTE4 (r = -0.831). Thus, although LTD4 and LTE4 are though to act on the same or similar receptors, the pattern of pharmacologic reversal at comparable levels of airway obstruction differs for these two agonists.