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Asthma Research Group, Smooth Muscle Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
We examined the ionic mechanisms underlying
the responses of canine trachealis to superoxide (generated in vitro by
using xanthine oxidase or added exogenously) and peroxide (generated spontaneously in vitro by the dismutation of superoxide or added exogenously). Although neither had any effect on resting tone, both
triggered relaxations in carbachol-precontracted tissues. These
relaxations were eliminated by catalase but were much less sensitive to
the hydroxyl radical scavenger dimethylthiourea, indicating they were
mediated primarily by peroxide. These relaxations were decreased in
magnitude and/or slowed by nifedipine
(10
6 M), ouabain
(106 M), or tetraethylammonium (25 mM),
but not by 4-aminopyridine (5 mM), and were small or absent in tissues
precontracted with 30 mM KCl. Finally, peroxide triggered membrane
hyperpolarization and elevated cytosolic concentration of
Ca2+ (primarily via release from the internal store). Thus
peroxide-mediated relaxations seem to involve Ca2+ release,
opening of Ca2+-dependent K+ channels,
hyperpolarization, closure of Ca2+ channels, and
relaxation. In addition, some other free radical (hydroxyl radical?)
may activate the Na+-K+ pump, also
hyperpolarizing the membrane and causing relaxation.
reactive oxygen species; free radicals; sarcoplasmic reticulum; contraction/relaxation
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