Abstract
In a recent clinical study, tranilast, an anti-allergic agent, was shown to reduce the rate of coronary restenosis after percutaneous transluminal coronary angioplasty, although the mechanism of this effect is unclear. The present study was undertaken to investigate the effects of tranilast on contraction and Ca 2+ movement of the coronary arteries. We characterized the effects of tranilast on isometric force and aequorin-estimated intracellular Ca 2+ concentrations ([Ca 2+] i) of porcine coronary artery strips. Tranilast concentration-dependently (10–500 μM) inhibited histamine (3×10 −5 M)-induced contraction of the coronary arteries. A similar tendency was observed in the response to high K + (30 mM) stimulation. Histamine caused phasic and tonic increases in [Ca 2+] i, and high K + caused a tonic increase in [Ca 2+] i of smooth muscle, both of which were significantly suppressed in the presence of tranilast. These results suggest that tranilast inhibits the contraction of coronary arteries by inhibiting both Ca 2+ influx from extracellular environment and Ca 2+ release from intracellular Ca 2+ stores, which might be related to its preventive effect on restenosis after coronary angioplasty.
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