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Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242
The inducible isoform of nitric oxide synthase
(iNOS) is expressed after systemic administration of lipopolysaccharide
(LPS). The importance of expression of iNOS in blood vessels is poorly defined. Because nitric oxide from iNOS may alter vasomotor function, we examined effects of LPS on vasomotor function in carotid arteries from iNOS-deficient mice. We studied contraction of the carotid artery
from wild-type and iNOS-deficient mice in vitro 12 h after injection of
LPS (20 mg/kg ip). Contractile responses to
PGF2
(3-30 µM) and
thromboxane A2 analog (U-46619;
3-100 nM) were evaluated using vascular rings from mice treated
with vehicle or LPS. Maximum force of contraction generated by rings in
response to PGF2
was 0.39 ± 0.02 and 0.25 ± 0.01 (SE) g (n = 14) in vehicle and LPS-treated wild-type mice, respectively
(P < 0.001 vs. vehicle). Thus LPS
reduced constrictor responses in wild-type mice. Thiocitrulline and
aminoguanidine (inhibitors of iNOS) improved contractile responses from
LPS-treated wild-type vessels. Indomethacin also improved constrictor
responses in arteries from wild-type mice injected with LPS. In
contrast, contraction of the carotid arteries in response to
PGF2
and U-46619 was not
impaired in LPS-treated iNOS-deficient mice, and contraction was not
altered by inhibitors of iNOS. Expression of iNOS mRNA was confirmed
using RT-PCR in carotid arteries from wild-type mice after injection of
LPS but not vehicle. PCR products for iNOS were not observed in
iNOS-deficient mice. These findings provide the first direct evidence
that iNOS mediates impairment of vascular contraction after treatment
with LPS.
carotid artery; acetylcholine; vasoconstriction; reverse transcriptase-polymerase chain reaction; lipopolysaccharide
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