PULMONARY ACTIONS OF THE NEUROKININ(1)-SPECIFIC AGONIST [SAR(9),MET(O-2)(11)]-SUBSTANCE-P

We examined the relationship between airway obstruction and plasma ext ravasation produced by the intravenous administration of the selective NK1 receptor agonist [Sar(9), Met(O-2)(11)]-substance P(SP). Consciou s guinea-pigs were injected with Evans' blue dye followed by intraveno us [Sar(9),Met(O-2)(11)]-SP. Animals were killed 3 min later and airwa y obstruction, determined via excised lung gas volumes, and plasma ext ravasation in the trachea, mainstem bronchi and intrapulmonary airways quantitated. Maximal plasma protein extravasation occurred at a dose about 30 times less than that required to elicit airway obstruction. N either the neutral endopeptidase (NEP) inhibitor, thiorphan, or the an giotensin-converting enzyme (ACE) inhibitor, captopril, altered the ex travasation response to [Sar(9),Met(O-2)(11)]-SP. However, thiorphan a lone or combined with captopril produced a small but significant poten tiation of the airway obstructive response. The marked difference betw een pulmonary gas trapping and Evans' blue extravasation responses sug gest that [Sar(9),Met(O-2)(11)]-SP-induced airway obstruction is not s econdary to increased pulmonary edema.