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DOI: 10.1055/s-2002-34934
© Georg Thieme Verlag Stuttgart · New York
Mechanisms of Relaxant Action of a Pyranocoumarin from Peucedanum japonicum in Isolated Rat Thoracic Aorta
Publication History
Received: January 25, 2002
Accepted: May 5, 2002
Publication Date:
21 October 2002 (online)
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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.
Key words
Peucedanum japonicum Thunb. - Umbelliferae - (+)-cis-4′-O- acetyl-3′-O-angeloylkhellactone - vasorelaxation (rat aorta)
References
- 1 Berridge M J. Capacitative calcium entry. Biochem. J.. 1995; 312 1-11
- 2 Himpens B, De Smedt H, Cstells R. Kinetics of nucleo-cytoplasmic transients in DDT1MF-2 cells. Am. J. Physiol.. 1992; 260 C978-85
- 3 Chandra S, Kable E PW, Morrison G H, Webb W W. Calcium sequestration in the Golgi apparatus of cultured mammalian cells revealed by laser scanning confocal microscopy and ion microscopy. J. Cell Sci.. 1990; 100 742-52
- 4 Felder C C, Singer-Lahat D, Mathes C. Voltage-independent calcium channels. Regulation by receptor and intracellular calcium stores. Biochem. Pharmacol.. 1994; 48 1997-2004
- 5 Vanhoutte P M. Endothelium and control of vascular function. Hypertension.. 1989; 13 658-67
- 6 De Mey J G, Claeys M, Vonhoutte P M. Endothelium dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery. J. Pharmacol. Exp. Ther.. 1982; 222 166-73
- 7 Palmer R MJ, Ferrige A G, Moneada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987; 327 524-6
- 8 Duh C Y, Wang S K, Wu Y C. Cytotoxic pyranocoumarins from the aerial parts of Peucedanum japonicum . Phytochemistry. 1991; 30 2812-4
- 9 Ikeshiro Y, Mase I, Tomita Y. Dihydropyranocoumarins from roots of Peucedanum japonicum . Phytochemistry.. 1992; 31 4303-6
- 10 Ikeshiro Y, Mase I, Tomita Y. Coumarins glycosides from Peucedanum japonicum . Phytochemistry. 1994; 35 1339-41
- 11 Moore P K, Al-Swateh O A, Chong N WS, Evans R, Mirza-Zadeh S, Gibson A. L-N G-nitroarginine (L-NOARG) inhibits endothelium dependent vasodilatation in the rabbit aorta and perfused rat mesentery. Br. J. Pharmacol.. 1989; 98 905-14
- 12 Beny J L, Brunet P C. Neither nitric oxide nor nitroglycerin accounts for all the characteristics of endothelially mediated vasodilatation of pig coronary arteries. Blood Vessels. 1988; 25 3-9
- 13 Feletou M, Vanhoutte P M. Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br. J. Pharmacol.. 1988; 93 515-4
- 14 Karaki H, Nakagawa H, Urakawa N. Comparative effects of verapamil and sodium nitroprusside on contraction and 45Ca2+ uptake in the smooth muscle of rabbit aorta, rat aorta and guinea pig taenia coli. Br. J. Pharmacol.. 1984; 81 393-4
- 15 Bolton T B. Mechanisms of action of transmitters and other substance on smooth muscle. Physiol. Rev.. 1979; 59 607-18
- 16 Meisheri K D, Cipkus-Dubray L A, Oleynek A J. A sensitive in vitro functional assay to detect K+ channel-dependent vasodilators. J. Pharmacol. Exp. Ther.. 1990; 24 251-61
Dr. Hyun Sun Lee
Cardiovascular Research Laboratory
Korea Research Institute of Bioscience and Biotechnology
P.O. Box 115, Yusong, Taejon 305-333
Korea
Email: leehs@mail.kribb.re.kr
Fax: +82-42-861-2675
Phone: +82-42-860-4314