EDRF-release and Ca++-channel blockade by magnolol, an antiplatelet agent isolated from Chinese herb ,in rat thoracic aorta

Magnolol is an antiplatelet agent isolated from Chinese herb Magnoliaofficinalis. It inhibited norepinephrine (NE, 3 μM)-induced phasic and tonic contractions in rat thoracic aorta. At the plateau of the NE-induced tonic contraction, addition of magnolol caused two phases (fast and slow) of relaxation. These two relaxations were concentration-dependent (10–100 μg/m1), and were not inhibited by indomethacin (20 μM). The fast relaxation was completely antagonized by hemoglobin (10 μM) and methylene blue (50 μM), and disappeared in de-endothelialized aorta while the slow relaxation was not affected by the above treatments. Magnolol also inhibited high potassium (60 mM)-induced, calcium-dependent (0.03 to 3 mM) contraction of rat aorta in a concentration-dependent manner. 45Ca++ influx induced by high potassium or NE was markedly inhibited by magnolol. Cyclic GMP, but not PGI2, was increased by magnolol in intact, but not in de-endothelialized aorta. It is concluded that magnolol relaxed vascular smooth muscle by releasing endothelium-derived relaxing factor (EDRF) and by inhibiting calcium influx through voltage-gated calcium channels.