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1 Department of Exercise Science and 2 Free Radical and Radiation Biology Program, University of Iowa, Iowa City, Iowa 52242
This work tested the hypotheses that
splanchnic oxidant generation is important in determining heat
tolerance and that inappropriate ·NO production may be involved in
circulatory dysfunction with heat stroke. We monitored colonic
temperature (Tc), heart rate, mean arterial pressure, and
splanchnic blood flow (SBF) in anesthetized rats exposed to 40°C
ambient temperature. Heating rate, heating time, and thermal load
determined heat tolerance. Portal blood was regularly collected for
determination of radical and endotoxin content. Elevating
Tc from 37 to 41.5°C reduced SBF by 40% and stimulated
production of the radicals ceruloplasmin, semiquinone, and
penta-coordinate iron(II) nitrosyl-heme (heme-·NO). Portal endotoxin
concentration rose from 28 to 59 pg/ml (P < 0.05).
Compared with heat stress alone, heat plus treatment with the nitric
oxide synthase (NOS) antagonist
N
-nitro-L-arginine methyl
ester (L-NAME) dose dependently depressed heme-·NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF,
increased portal endotoxin concentration, and reduced heat tolerance
(P < 0.05). The NOS II and diamine oxidase antagonist
aminoguanidine, the superoxide anion scavenger superoxide dismutase,
and the xanthine oxidase antagonist allopurinol slowed the rates of
heme-·NO production, decreased ceruloplasmin and semiquinone levels,
and preserved SBF. However, only aminoguanidine and allopurinol
improved heat tolerance, and only allpourinol eliminated the rise in
portal endotoxin content. We conclude that hyperthermia stimulates
xanthine oxidase production of reactive oxygen species that activate
metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for
normal stress tolerance, whereas overproduction of ·NO may contribute
to the nonprogrammed splanchnic dilation that precedes vascular
collapse with heat stroke.
oxidative stress; nitrosative stress; free radicals; ischemia; heat stroke; electron paramagnetic resonance; endotoxemia
Deceased 3 June 2000.
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