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Department of Pediatrics, University of Iowa, Iowa City, Iowa, 52242
Activation of a
Cl
current is critical to
agonist-induced activation of rat aortic smooth muscle contraction.
Substituting extracellular
Cl
with 130 mM
methanesulfonate (8 mM
Cl
) increases the
contractile response to norepinephrine (NE) but not to KCl. We
hypothesized that endothelial factors modulate this effect. Removing
the endothelium (rubbing) or treatment with N-nitro
L-arginine
(L-NNA) markedly increased the
potentiation of NE-induced contraction by
low-Cl
buffer. Indomethacin
had no effect. The previously demonstrated ability of
Cl
-channel blockers (DIDS,
anthracene-9-carboxylic acid, niflumic acid) or
Cl
transport inhibitors
(bumetanide, bicarbonate-free buffer) to inhibit responses to NE was
not altered by L-NNA.
Low-Cl
buffer alone did not
contract intact rings but produced nifedipine-sensitive contractile
responses after rubbing or L-NNA
treatment. These data suggest that the
Cl
conductance of smooth
muscle in intact blood vessels is low but increases with withdrawal of
reduced nitric oxide (NO') or agonist stimulation. Rubbing or
L-NNA increased the sensitivity
of rings to KCl but not to NE. Nifedipine reduced both sensitivity and maximum response to NE in intact vessels.
L-NNA increased the maximum
response to NE in nifedipine-treated rings without changing sensitivity. We conclude that although NO' affects both the
voltage-dependent and voltage-independent components of contraction,
sensitivity to NE is determined by the voltage-dependent portion. The
voltage change required for a full response to NE is dependent on
activation of a Cl
current
that may be under the tonic regulatory influence of NO'.
nitric oxide; N-nitro-L-arginine; nifedipine; indomethacin; methanesulfonate
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