Mechanisms of Relaxant Action of a Pyranocoumarin fromPeucedanum japonicumin Isolated Rat Thoracic Aorta

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Abstract
The CHCl3-soluble fraction obtained from the MeOH extract of Peucedanum japonicum Thunb. inhibited phenylephrine-induced vasoconstriction in isolated rat thoracic aorta. We isolated a vasorelaxing compound, as one of the bioactive components, which was identified as (+)-cis-4′-O-acetyl-3′-O-angeloylkhellactone (1), a pyranocoumarin, and examined the mechanisms of vasorelaxant effect caused by 1. This compound (1) (10-6 - 10-4 M) concentration-dependently relaxed the isolated rat thoracic aorta pre-contracted with phenylephrine (PE). This vasorelaxant potency was diminished by endothelial removal (by 20 %), L-N G-nitro-arginine or methylene blue (MB), but not indomethacin treatment. These findings indicate that the vasorelaxant effect of 1 was partially endothelium dependent and mediated by nitric oxide and cyclic GMP pathway. To determine if the effect of 1 was mediated through the activation of some of the receptors known to lead to vascular relaxation, the effects of atropine, triprolidine and propranolol were determined. 1-induced vasorelaxation was not affected by atropine, triprolidine and propranolol. Compound 1 inhibited high potassium (80 mM)-induced, calcium-dependent contractions in a concentration-dependent manner. But it slightly relaxed the rat aorta precontracted with PE in the presence of nifedipine, a blocker of voltage-operated calcium channels. Tetraethylammonium (TEA, a non-specific K+ channel blocker) did not affect the vasodilatory effect of 1 against PE-induced contraction. Mechanisms of the vasorelaxant effect of 1 were multiple, including endothelium dependence and Ca2+ channel blockade.

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