The pharmacological effects of osthole on isolated rat thoracic aorta were examined. Osthole inhibited norepinephrine (NE, 3 μM)-induced phasic and tonic contractions in rat thoracic aorta in a concentration-dependent manner (40-200 μM). The tonic contraction elicited by NE was also relaxed by the addition of osthole. This relaxing effect of osthole was not affected by indomethacin (20 μM) and was still observed in endothelium-denuded rat aorta. Methylene blue (50 μM) partially antagonized this relaxing effect of osthole. In high-K+ medium (80 mM), the Ca2+ (0.03-3 mM)-induced vasocontraction was inhibited concentration dependently by osthole (20-100 μM). Addition of osthole (100 μM) at the plateau of the K+ (80 mM)-induced contraction caused relaxation. Methylene blue (50 μM) did not antagonize this relaxation. In Ca2+-free medium, the caffeine (10 mM)-induced phasic contraction was also suppressed by osthole in a concentration-dependent manner. Although the cAMP level was not changed by osthole, the cGMP level of rat aorta was increased by osthole in a concentration-dependent manner. The increase in cGMP level caused by osthole was completely blocked by methylene blue. [3H]Inositol monophosphate formation caused by NE was not affected by osthole at a concentration of 200 μM. The 45Ca2+ influx elicited by either NE or high K+ was inhibited by osthole in a concentration-dependent manner. It is concluded that osthole relaxes rat thoracic aorta by virtue of its Ca2+-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.
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