DOI QR코드

DOI QR Code

Effects of Ginsenoside Rg3 Epimers on Swine Coronary Artery Contractions

  • Kim, Jong-Hoon (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University)
  • Published : 2005.09.01

Abstract

The previous reports demonstrated that ginseng saponins, active ingredient of Panax ginseng, inhibited blood vessel contraction induced by various hormones or high $K^+$. Recently, we demonstrated that 20(R)- and 20(S)-ginsenoside $Rg_3$. regulate ion channel activities with differential manners. The aim of this study was to examine whether ginsenoside $Rg_3$ isomers also show differential effects on swine coronary artery contractionresponses induced by high $K^+$, serotonin (5-HT) or acetylcholine. Treatment of 20(S)- but not 20(R)-ginsenoside $Rg_3$ caused a concentration-dependent relaxation of coronary artery contracted by 25mM KCI. 20(S)- and 20(R)-ginsenoside $Rg_3$ induced significant relaxations of coronary artery contraction induced by 5-HT $(3{\mu}M)$ in the presence of endothelium with concentration-dependent manner and, also in the absence of endothelium only 20(S)-ginsenoside $Rg_3$ induced a strong Inhibition of coronary artery contraction induced by 5-HT in a concentration-dependent manner. 20(S)-ginsenoside $Rg_3$ caused relaxation of coronary artery in the absence and presence of endothelium. In contrast, treatment of 20(S)- and 20(R)-ginsenoside $Rg_3\;(100{\mu}M)$ did not show significant inhibition of coronary artery contraction induced by acetylcholine $(0.01\;to\;30{\mu}M)$ in the presence of endothelium, whereas both isomers caused significant inhibition of coronary artery contraction induced by acetylcholine $(0.01\;to\;30{\mu}M)$ in the absence of endothelium in a concentration-dependent manner. These findings indicate that 20(S)-or 20(R)-ginsenoside $Rg_3$ exhibits differential relaxation eff3cts of swine coronary artery contractions caused by high $K^+$, acetylcholine, and 5-HT treatment and that this differential vasorelaxing effects of ginsenoside $Rg_3$ isomers also might be dependent on endothelium.

Keywords

References

  1. Dubbert, P.M., Carithers, T. and Sumner, A.E.: Obesity, physical inactivity, and risk for cardiovascular disease. Am. J. Med. Sci. 324, 116-126 (2002) https://doi.org/10.1097/00000441-200209000-00002
  2. Grech, E.D. : Pathophysiology and investigation of coronary artery disease. BMJ. 326, 1027-1030 (2003) https://doi.org/10.1136/bmj.326.7397.1027
  3. Cowie, M.R., Mosterd, A. and Wood, D.A. : The epidemiology of heart failure. Eur. Heart J. 18, 208-25 (1997) https://doi.org/10.1093/oxfordjournals.eurheartj.a015223
  4. Baker, D., Bahler, R. and Finkelhor, R. : Screening for left ventricular systolic dysfunction among patients with risk factors for heart failure. Am. Heart J. 146, 736-740 (2003) https://doi.org/10.1016/S0002-8703(03)00396-X
  5. Rasmussen, S., Abildstrom, S. and Rosen, M. : Case-fatality rates for myocardial infarction declined in Denmark and Sweden during 1987.1999. J. Clin. Epidemiol. 57, 638-46 (2004) https://doi.org/10.1016/j.jclinepi.2003.10.013
  6. Sohn, E.S., Huh, B.Y., Park, S.C., Park, C.W. and Kim, H.J. : The effect of ginseng on blood pressure in spontaneous hypertensive rat and essential hypertension. Proceedings of the 3rd International Ginseng Symposium. Korean Ginseng Research. Institute, Seoul, Korea. 1-3 (1980)
  7. Kim, N.D., Kang, S.Y. and Schini, V.B. : Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta. Gen. Pharmacol. 25, 1071-1077 (1994) https://doi.org/10.1016/0306-3623(94)90121-X
  8. Chen, X .. , Gillis, C.N. and Moalli, R. : Vascular effects of ginsenosides in vitro. Br. J. Pharmacol. 82, 485-491 (1984) https://doi.org/10.1111/j.1476-5381.1984.tb10784.x
  9. Kim, N.D., Kang, S.Y., Park, J.H. and Schini-Kerth, V.B. : Ginsenoside $Rg_3$, mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of $K^+$ channels. Eur. J. Pharmacol. 367, 41-49 (1998) https://doi.org/10.1016/S0014-2999(98)00898-X
  10. Nah, S.Y. : Ginseng; recent advances and trends. J. Gin. Res. 21, 1-12 (1997)
  11. Kitagawa, I., Yoshikawa, M., Yoshimura, M., Hayash, T. and Taniyama, T. : Chemical studies on crude drug procession. Yakugaku. Zasshi. 103, 612-622 (1983)
  12. Palmer, R.M., Ashton, D.S. and Moncada, S. : Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 333, 664-666 (1988) https://doi.org/10.1038/333664a0
  13. Sumner, M.J. : Characterization of the 5-HT receptor mediating endothelium-dependent relaxation in porcine venacava. Br. J. Pharmacol. 102,938-942 (1991) https://doi.org/10.1111/j.1476-5381.1991.tb12280.x
  14. Martin, G.R., Bolofo, M.L. and Giles, H. : Inhibition of endothelium-dependent vasorelaxation by arginine analogues: a pharmacological analysis of agonist and tissue dependence. Br. J. Pharmacal. 105, 643-652 (1992) https://doi.org/10.1111/j.1476-5381.1992.tb09033.x
  15. Wallis, S.J. and Martin, W. : Conditions permitting suppres- sion of stretch-induced and vasoconstrictor tone by basal nitric oxide activity in porcine cerebral artery. Br. J. Pharmacol. 130, 567-574 (2000) https://doi.org/10.1038/sj.bjp.0703351
  16. MaassenVanBrink, A., van den Broek, R.W.M., de Vries, R., Upton, N., Parsons, A.A. and Saxena, P.R. : The potential antimigraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan. Cephalalgia. 20, 538-545 (2001) https://doi.org/10.1046/j.1468-2982.2000.00078.x
  17. Nyborg, N.C. and Mikkelsen, E.O. : 5-Hydroxytryptamine does not release endothelium-derived relaxing factor in rat isolated coronary arteries. Eur. J Pharmacol. 186, 295-300 (1990) https://doi.org/10.1016/0014-2999(90)90447-E
  18. Stuehr, D.J. and Griffith, O.W. : Mammalian nitric oxide synthases. Adv. Enzymol. 65, 287-346 (1992)
  19. Sward, K., Josefsson, M., Lydrup, M.L. and Hellstrand, P.: Effects of metabolic inhibition on cytoplasmic calcium and contraction in smooth muscle of rat portal vein. Acta. Physio.l Scand. 148, 265-272 (1993) https://doi.org/10.1111/j.1748-1716.1993.tb09557.x
  20. Yamano, M., Ito, H. and Miyata, K. : Species differences in the 5-hydroxytryptamine-induced contraction in the isolated distal ileum. Jpn. J. Pharmacol. 74, 267-274 (1997) https://doi.org/10.1254/jjp.74.267
  21. Hinton, J.M., Hill, P., Jeremy, J. and Garland, C. : Signalling pathways activated by 5-HT (lB)/5-HT (lD) receptors in native smooth muscle and primary cultures of rabbit renal artery smooth muscle cells. J. Vas.c Res. 37, 457-468 (2000) https://doi.org/10.1159/000054078
  22. Nieto, J.E., Snyder, J.R., Kollias-Baker, C. and Stanley, S. : In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses. Am. J. Vet. Res. 61, 1561-1565 (2000) https://doi.org/10.2460/ajvr.2000.61.1561