Mechanisms of Relaxant Action of a Pyranocoumarin from Peucedanum japonicum in Isolated Rat Thoracic Aorta

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.

Peucedanum japonicum Thunb. - Umbelliferae - (+)-cis-4′-O- acetyl-3′-O-angeloylkhellactone - vasorelaxation (rat aorta)

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