Neurogenic plasma leakage in mouse airways

1 This study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance P on microva scular plasma leakage in the trachea and lungs of male pathogen-free C57BL/ 6 mice. 2 Single bolus intravenous injections of capsaicin (0.5 and 1 mu mol kg(-1) , i.v.) or substance P (1, 10 and 37 nmol kg(-1), i.v.) failed to induce si gnificant leakage in the trachea. assessed as extravasation of Evans blue d ye, but did induce leakage in the urinary bladder and skin. 3 Pretreatment with captopril (2.5 mg kg(-1), i.v.), a selective inhibitor of angiotensin converting enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg(-1), i.v.), a selective inhibitor of neutral end opeptidase (NEP), increased baseline leakage of Evans blue In the absence o f any exogenous inflammatory mediator. The increase was reversed by the bra dykinin B-2 receptor antagonist Hoe 140 (0.1 mg kg(-1), i.v,). 4 After pretreatment with phosphoramidon and captopril, capsaicin increased the Evans blue leakage above the baseline in the trachea, but not in the l ung. This increase was reversed by the tachykinin (NK1) receptor antagonist SR 140333 (0.7 mg kg(-1), i.v.), but not by the NK2 receptor antagonist SR 48968 (1 mg kg(-1), i.v.). 5 Experiments using Monastral blue pigment as a tracer localized the leakag e to postcapillary venules in the trachea and intrapulmonary bronchi, altho ugh the labelled vessels were less numerous in mice than in comparably trea ted rats. Blood vessels of the pulmonary circulation were not labelled. 6 We conclude that neurogenic inflammation can occur in airways of pathogen -free mice, but only after the inhibition of enzymes that normally degrade inflammatory peptides. Neurogenic inflammation does not involve the pulmona ry microvasculature.