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1 Women's Health Research Center, University of Colorado Health Sciences Center, and 3 Department of Anthropology, University of Colorado at Denver, Denver, Colorado 80262; and 2 Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico 00936
Chronic hypoxia alters contractile
sensitivity of isolated arteries to 
-adrenergic stimulation and
other agonists. However, most studies have been performed in thoracic
aortas or other large vessels making little contribution to vascular
resistance in their respective circulations. To determine the effect of
chronic hypoxia on the vasoconstrictor response in a small,
resistance-sized vessel, we studied second and third generation middle
cerebral arteries (MCA; ~75-µm internal diameter before mounting).
MCA were isolated from normoxic (inspired oxygen = 125 Torr) and
hypoxic (8 wk at 3,960 m; inspired oxygen = 90 Torr) guinea pigs,
and their vasoconstrictor responses were determined to the
thromboxane mimetic U-46619 by using dual-pipette video microscopy.
Arteries from hypoxic animals had greater contractile sensitivity to
U-46619 compared with those of the normoxic animals (
log
EC50 = 7.86 ± 0.11 vs. 7.62 ± 0.06, respectively, P < 0.05). Addition of the nitric oxide
(NO) inhibitor nitro-L-arginine (200 µM) to the vessel
bath eliminated the differences in contractile sensitivity between the
MCA from the normoxic and chronically hypoxic groups. Supplementation
with L-arginine in the drinking water sufficient to raise
plasma L-arginine levels 41% reduced MCA contractile
sensitivity to U-46619 in the normoxic group (log
EC50 = 7.22 ± 0.31, P < 0.05 compared with the nonsupplemented normoxic group) but not in the
chronically hypoxic group. These results show that chronic hypoxia
increases the sensitivity of the MCA to the vasoconstrictor U-46619,
likely because of a reduction in NO production and/or activity.
vascular reactivity; nitric oxide; thromboxane; L-arginine; cerebral circulation; middle cerebral arteries
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