The role of
oxygen radicals in
exsanguination-induced bronchoconstriction (EIB) was investigated using intratracheal instillation of
antioxidants. In series 1, 49 guinea pigs (331 +/- 6 g) were employed in the functional study. These animals were divided into seven groups: control,
superoxide dismutase (SOD),
catalase (CAT), erythrocytes (RBCs), N-[2-(2-oxo-1-imidazolindinyl)-ethyl]-
N'-phenylurea (EDU),
ruthenium red (RR), and systemic
capsaicin pretreatment. SOD, CAT, RBCs, and EDU are
antioxidants, whereas RR is a blocker of transmembrane Ca2+ fluxes. All agents except
capsaicin were administered by intratracheal instillation 30 min before
exsanguination; each animal of the last group received a 5-day subcutaneous
capsaicin pretreatment. All animals were anesthetized, sternotomized, and exsanguinated. Before as well as 1-30 min after
exsanguination, the maximal expiratory flow maneuver was performed and the minimal volume was obtained. In the control group,
exsanguination caused gradual decreases in the maximal expiratory flow at 50% baseline total lung capacity, forced expiratory volume at 0.1 s, and total lung capacity as well as a gradual increase in the minimal volume, indicating that EIB becomes more severe with time. EIB was significantly ameliorated by intratracheal instillation of SOD, CAT, RBCs, EDU, and RR, and it was almost abolished by systemic
capsaicin pretreatment. In series 2, however, inactivated CAT did not significantly affect EIB. We determined tracheal
neutral endopeptidase (NEP) activity in 23 animals. Thirty minutes after
exsanguination, there was a significant decrease in NEP activity in the control but not the CAT group. These results indicate that EIB is modulated by
oxygen radicals, which inactivate NEP.(ABSTRACT TRUNCATED AT 250 WORDS)