VASORELAXATION OF RAT THORACIC AORTA CAUSED BY OSTHOLE ISOLATED FROM ANGELICA-PUBESCENS

The pharmacological effects of osthole on isolated rat thoracic aorta were examined. Osthole inhibited norepinephrine (NE, 3-mu-M)-induced phasic and tonic contractions in rat thoracic aorta in a concentration-dependent manner (40-200-mu-M). 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-mu-M) and was still observed in endothelium-denuded rat aorta. Methylene blue (50-mu-M) 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-mu-M). Addition of osthole (100-mu-M) at the plateau of the K+ (80 mM)-induced contraction caused relaxation. Methylene blue (50-mu-M) 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. [H-3]Inositol monophosphate formation caused by NE was not affected by osthole at a concentration of 200-mu-M. The Ca-45(2+) 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.