Effects of Flufenamic Acid on Smooth Muscle of the Carotid Artery Isolated from Spontaneously Hypertensive Rats

Endothelium-removed carotid artery strips from stroke-prone spontaneously hypertensive rats spontaneously developed a tonic myogenic contraction. Flufenamic acid reduced the resting tone observed during superfusion with Tyrode's solution, in a concentration-dependent manner. Flufenamic acid als...

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Bibliographic Details
Published in:Journal of Smooth Muscle Research 2002, Vol.38(1,2), pp.39-50
Main Authors: Shimamura, Keiichi, Zhou, Ming, Ito, Yasuko, Kimura, Shinichi, Zou, L.-B., Sekiguchi, Fumiko, Kitamura, Kenji, Sunano, Satoru
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Ca2+ current
Calcium - metabolism
Calcium Channels, L-Type - physiology
Carotid artery
Carotid Artery, Common - drug effects
Carotid Artery, Common - physiology
Flufenamic acid
Flufenamic Acid - pharmacology
K+ current
Male
Membrane Potentials - drug effects
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - physiology
Patch-Clamp Techniques
Potassium - metabolism
Potassium Channels, Voltage-Gated - physiology
Rats
Rats, Inbred SHR
SHR
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Summary:Endothelium-removed carotid artery strips from stroke-prone spontaneously hypertensive rats spontaneously developed a tonic myogenic contraction. Flufenamic acid reduced the resting tone observed during superfusion with Tyrode's solution, in a concentration-dependent manner. Flufenamic acid also inhibited contractions produced by high-K+ solutions in a concentration-dependent manner. The resting membrane potential of smooth muscle cells in the artery was around -32 mV, with occasional oscillatory potentials. Flufenamic acid hyperpolarized the membrane in a concentration-dependent manner. The voltage-dependent outward currents recorded in isolated cells with micropipettes filled with high-K+ solution (holding potential, -60 mV) were enhanced by flufenamic acid and inhibited by tetraethylammonium. When the recording micropipette was filled with high Cs+ to inhibit the K+-current, depolarizing step pulses evoked nifedipine-sensitive inward currents. Flufenamic acid inhibited the inward currents. These results indicate that flufenamic acid inhibits the spontaneous active tone of the carotid artery by inhibiting L-type Ca2+-channels and possibly by membrane hyperpolarization through activation of the voltage-dependent K+-channels.
ISSN:0916-8737
1884-8796
DOI:10.1540/jsmr.38.39