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 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.
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan. shimamu@hoku-iryo-u.ac.jp
Keiichi
K
Shimamura
Ming
M
Zhou
Yasuko
Y
Ito
Shinichi
S
Kimura
L B
LB
Zou
Fumiko
F
Sekiguchi
Kenji
K
Kitramura
Satoru
S
Sunano
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000502:physiology; D005439:Flufenamic Acid / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020746:Calcium Channels, L-Type; D024642:Potassium Channels, Voltage-Gated; D005439:Flufenamic Acid; D011188:Potassium; D002118:Calcium