장미근(薔薇根) 메탄올 추출물의 혈관이완 기전에 대한 연구

Study on the Mechanism of Vascular Relaxation of Methanol Extract of Rose multiflora Radix

  • 김대중 (원광대학교 한의학전문대학원) ;
  • 조남근 (원광대학교 한의학전문대학원) ;
  • 이준경 (원광대학교 한의학전문대학원) ;
  • 조려화 (원광대학교 한의학전문대학원) ;
  • 이혁 (원광대학교 한의학전문대학원) ;
  • 안준석 (원광대학교 한의학전문대학원) ;
  • 엄재연 (원광대학교 한의과대학 한의학과) ;
  • 조규원 (원광대학교 한의과대학 한의학과) ;
  • 나한일 (원광대학교 한의과대학 한의학과) ;
  • 경은호 (원광대학교 한의과대학 한의학과) ;
  • 강대길 (원광대학교 한의학전문대학원) ;
  • 이호섭 (원광대학교 한의학전문대학원)
  • Kim, Dae-Joong (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Jo, Nam-Geun (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Lee, Jun-Kyoung (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Cao, Li-Hua (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Lee, Hyuck (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • An, Jung-Seok (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Um, Jae-Yeon (Department of Oriental Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Joe, Gye-One (Department of Oriental Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Na, Han-Il (Department of Oriental Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Kyung, Eun-Ho (Department of Oriental Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Kang, Dae-Gil (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Lee, Ho-Sub (Professional Graduate School of Oriental Medicine, Wonkwang University)
  • 발행 : 2007.04.25

초록

Vascular tone plays an important role in the regulation of blood pressure. In the present study, the methanol extract of Rosae multiflora Radix (MRM) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pretreatment of the endothelium-intact aortic tissues with $N^G$-nitro-L-arginine methly ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-${\alpha}$]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by MRM, respectively. But, the relaxation effect of MRM was not blocked by indomethacine, glibenclamide, tetraethylammonium (TEA), verapamil, diltiazem, atropine, and propranolol, respectively. Moreover, incubation of endothelium-intact aortic rings with MRM increased the production of cGMP. Taken together, the present results suggest that MRM relaxes vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling. These results would be useful for further study to MRM on animal models with cardiovascular diseases.

키워드

참고문헌

  1. Levi, R. Therapies for perioperative hypertension: Pharmacodynamic considerations: Acta Anaesthesiol. Scand. Suppl. 37(99):16-19, 1993
  2. Bosnjak, Z.J. Ion channels in vascular smooth muscle: Anesthesiology. 79: 1392-401, 1993 https://doi.org/10.1097/00000542-199312000-00031
  3. Kim, S.H., Kang, K.W., Kim, K.W., Kim, N.D. Procyanidins in Crataegus extract evoke endothelium-dependent vasorelaxation in rat aorta: Life Sci. 67: 121-131, 2000 https://doi.org/10.1016/S0024-3205(00)00608-1
  4. Guerrero, M.F., Puebla, P., Carron, R., Martin, M.L., San Roman, L. Quercetin 3,7-dimethyl ether: a vasorelaxant flavonoid isolated from Croton schiedeanus: Schlecht. J. Pharm. Pharmacol. 54: 1373-1378, 2002 https://doi.org/10.1211/002235702760345455
  5. Kamata, K., Noguchi, M., Nagai, M.Hypotensive effects of lithospermic acid B isolated from the extract of Salviae miltiorrhizae radix in the rat: Gen. Phamacol. 25: 69-73, 1994
  6. Goto, H., Shimada, Y., Tanigawa, K., Sekiya, N., Shitani, T., Terasawa, K. Effect of Uncariae ramulus et Uncus on endothelium in spontaneously hypertensive rats: Am. J. Chin. Med. 27: 339-345, 1999 https://doi.org/10.1142/S0192415X99000380
  7. Chiou, W.F., Chang, P.C., Chou, C.J., Chen, C.F. Protein constituent contributes to the hypotensive and vasorelaxatant activities of Cordyceps sinensis: Life Sci. 66: 1369-1376, 2000 https://doi.org/10.1016/S0024-3205(00)00445-8
  8. Tanner, M.A., Bu, X., Steimle, J.A., Myers, P.R. The direct release of nitric oxide by gypenosides derived from the herb Gynostemma pentaphyllum: Nitric Oxide 3: 359-365, 1999 https://doi.org/10.1006/niox.1999.0245
  9. Kang, D.G., Lee, J.K., Choi, D.H., Sohn, E.J., Moon, M.K., Lee, H.S. Vascular relaxation by the methanol extract of Sorbus cortexvia NO/cGMP pathway: Biol. Pharm. Bull. 28(5):860-864, 2005 https://doi.org/10.1248/bpb.28.860
  10. 김창민, 신민교, 이경순, 안덕균. 完譯中藥大辭典 (8권). 서울, 도서출판 정담. pp 3673-3674, 1998
  11. Kim, S.Z., Kim, S.H., Park, J.K., Koh, G.Y., Cho, K.W. Presence and biological activity of c-type natriuretic peptide-dependent guanylate cyclase-coupled receptor in the penile corpus cavernosum: J. Urol. 159: 1741-1746, 1998 https://doi.org/10.1097/00005392-199805000-00104
  12. Palmer, R.M., Rees, D.D., Ashton, D.S., Moncada, S. L-arginineis the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation: Biochem. Biophys. Res. Commun. 153(3):1251-1256, 1998 https://doi.org/10.1016/S0006-291X(88)81362-7
  13. Meng, W., Ma, J., Ayata, C., Hara, H., Huang, P.L., Fishman, M.C., Moskowitz, M.A. Ach dilates pial arterioles in endothelial and neuronal NOS knockout mice by NO-dependent mechanisms: Am. J. Physiol. 271: H1145-H1150, 1996
  14. Furchgott, R.F., Vanhoutte, P.M. Endothelium-derived relaxing and contracting factors: FASEB J. 3(9):2007-2018, 1989 https://doi.org/10.1096/fasebj.3.9.2545495
  15. Suzuki, H., Chen, G., Yamamoto, Y., Miwa, K. Nitroarginine- sensitive and -insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery: Jpn. J. Physiol. 42(2):335-347, 1992 https://doi.org/10.2170/jjphysiol.42.335
  16. Furchgott, R.F., Vanhoutte, P.M. Endothelium-derived relaxing and contracting factors: FASEB J. 3: 2007-2018, 1989 https://doi.org/10.1096/fasebj.3.9.2545495
  17. Busse, R., Mulsch, A., Fleming, I., Hecker, M. Mechanism of nitric oxide release from the vascular endothelium: 87: V18-V25, 1993
  18. Warner, T.D., Mitchell, J.A. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic: FASEB. 18: 790-804, 2004 https://doi.org/10.1096/fj.03-0645rev
  19. Dubois, R.N., Abramson, S.B., Crofford, L., Gupta, R.A., Simson, L.S., Van De Putte, L.B.A., Lipsky, P.E. Cyclooxygenase in biology and disease. FASEB J. 12: 1063-1073, 1998 https://doi.org/10.1096/fasebj.12.12.1063
  20. Yamagishi, T., Yanagisawa, T., Taria, N. $Ca^{2+}$ influx induced by the agonist U46619 is inhibited by hyperpolarization induced by the $K^+$ channel opener cromakalim in canine coronary artery: Jpn J Pharmacal. 59: 291-299, 1992 https://doi.org/10.1254/jjp.59.291
  21. Yanagisawa, T., Yamagishi, T., Okada, Y. The hyperpolarization induced by $K^+$ channel openers inhibits $Ca^{2+}$ influx and release in coronary artery: Cardiovasc Drugs Ther. Suppl 3: 565-574, 1993
  22. 김영균, 고석신, 김종훈. 星香正氣散이 家兎의 頸動脈 平滑筋 緊張度 調節에 미치는 影響. 대한한의학회지 19(2):228-243, 1998
  23. Mikkelsen, E.O., Thastrup, O., Christensen, S.B. Effects of thapsigargin in isolated rat thoracic aorta: Pharmacol. Toxicol. 62: 7-11, 1988 https://doi.org/10.1111/j.1600-0773.1988.tb01835.x
  24. Delaflotte, S., Auguet, M., DeFeudis, F.V., Baranes, J., Clostre, F., Drieu, K., Braquet, P. Endothelium-dependent relaxations of rabbit isolated aorta produced by carbachol and by Ginkgo biloba extract: Biomed. Biochim. Acta. 43: S212-216, 1984