Mechanisms of relaxant action of a pyranocoumarin from Peucedanum japonicum in isolated rat thoracic aorta.
The CHCl(3) -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 Ca(2+) channel blockade.
Lee
Jong Wha
JW
Department of Environmental Health Science, Soonchunhyang University, Asan, Korea.
Roh
Tae Cheol
TC
Rho
Mun-Chual
MC
Kim
Young Kook
YK
Lee
Hyun Sun
HS
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D019661:Apiaceae; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D018517:Plant Roots; D039681:Pyranocoumarins / Q000008:administration & dosage / Q000494:pharmacology*; D011753:Pyrones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
C469046:4'-O-acetyl-3'-O-angeloylkhellactone; D003374:Coumarins; D010936:Plant Extracts; D039681:Pyranocoumarins; D011753:Pyrones; D014665:Vasodilator Agents