Ca⁺⁺-channel blocking effects of three coumarin compounds, isolated from Citrus grandis, in rat thoracic aorta

Xanthyletin, xanthoxyletin and suberosin are coumarin compounds isolated from Citrus grandis. These three coumarins relaxed the sustained tonic contraction in the rat aorta evoked by norepinephrine (NE, 3 μM) in a concentration-dependent manner. If the aorta was preincubated with these coumarins for 15 min, NE-induced phasic and tonic contractions were suppressed. The tonic contraction was inhibited by coumarins more markedly than phasic contraction. These coumarins also inhibited the sustained contraction evoked by NE in endothelium-denuded aorta. These coumarins and dicumarol inhibited Ca⁺⁺-induced contraction in high potassium (60 mM) medium, shifted the dose-response curve to the right and diminished the maximal response. The concentrations of coumarins that inhibited vasoconstriction induced by high K⁺ were much less than those required to inhibit the NE-induced response. Bay K 8644-induced contraction was also relaxed by coumarins and nifedipine. In the presence of nifedipine (10 μM), NE-induced contraction was relaxed by 100 μM, but not 25 μM of xanthyletin. Caffeine (10 mM)-induced transient contraction was not inhibited by these compounds. They did not elevate intracellular cGMP level of rat thoracic aorta. It is concluded that the coumarin compounds may inhibit both the voltage-dependent (nifedipine-sensitive) Ca⁺⁺ influx, and also the receptor-operated Ca⁺⁺ channel.