Intratracheal antioxidants attenuate exsanguination-induced bronchoconstriction in guinea pigs.
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)
Zhang
H Q
HQ
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536.
Lai
Y L
YL
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D006168:Guinea Pigs; D006470:Hemorrhage / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D012123:Pulmonary Ventilation; D014109:Total Lung Capacity; D014132:Trachea / Q000201:enzymology
D000975:Antioxidants; D015260:Neprilysin