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

• 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
• ISSN: 0916-8737; 1884-8796
• DOI: 10.1540/jsmr.38.39

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.