YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Vasorelaxing Effect of Isoflavonoids Via Rho-kinase Inhibition in Agonist-Induced Vasoconstriction

Isoflavonoids에 의한 혈관이완효과에 있어 Rho-kinase의 역할

  • Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
  • 제현동 (대구가톨릭대학교 약학대학 약물학 교실)
  • Published : 2006.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

The aim of present study was to investigate the possible influence of Rho-kinase inhibition on the plant-derived estrogen-like compounds-induced arterial relaxation. Agonist- or depolarization-induced vascular smooth muscle contractions involve the activation of Rho-kinase pathway. However there are no reports addressing the question whether this pathway is involved in genistein-or daidzein-induced vascular relaxation in rat aortae precontracted with phenylephrine or thromboxane $A_2$ mimetic U-46619. We hypothesized that Rho-kinase inhibition plays a role in vascular relaxation evoked by genistein or daidzein in rat aortae. Endothelium-intact and denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Genistein concentration-dependently inhibited phenylephrine or thromboxane $A_2-induced$ contraction regardless of endothelial function. Surprisingly, in the agonists-induced contraction, similar results were also observed in aortae treated with daidzein, the inactive congener for protein tyrosine kinase inhibition, suggesting that Rho-kinase might act upstream of tyrosine kinases in phenylephrine-induced contraction. In conclusion, in the agonists-precontracted rat aortae, genistein and daidzein showed similar relaxant response regardless of tyrosine kinase inhibition or endothelial function.

Keywords

References

  1. Hsieh, C. Y., Santell, R. C., Haslam, S. Z. and Helferich, W. G. : Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58, 3833 (1998)
  2. Martin, P. M., Horwitz, K. B., Ryan, D. S. and McGuire, W. L. : Phytoestrogen interaction with estrogen receptors in human breast cancer cells. Endocrinology 103, 1860 (1978) https://doi.org/10.1210/endo-103-5-1860
  3. Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., Van der Saag, P. T., Van der Burg, B. and Gustafsson, J. A. : Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252 (1998) https://doi.org/10.1210/en.139.10.4252
  4. Williams, J. K. and Clarkson, T. B. : Dietary soy isoflavones inhibit in vivo constrictor responses of coronary arteries to collagen-induced platelet activation. Coron. Artery Dis. 9, 759 (1998) https://doi.org/10.1097/00019501-199809110-00009
  5. Anderson, J. W., Johnstone, B. W. and Cook-Newell, M. E. : Meta- analysis of the effects of soy protein intake on serum lipids. N. Engl. J. Med. 333, 276 (1995) https://doi.org/10.1056/NEJM199508033330502
  6. Hodgson, J. M., Croft, K. D., Puddey, L. B., Mori, T. A. and Beilin, L. J. : Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum. J. Nutr. Biochem. 7, 664 (1996) https://doi.org/10.1016/S0955-2863(96)00133-7
  7. Mitchell, J. H. and Collins, A. R. : Effects of a soymilk supplement on plasma cholesterol levels and oxidative DNA damage in men-a pilot study. Eur. J. Nutr. 38, 143 (1999) https://doi.org/10.1007/s003940050055
  8. Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watanabe, S., Itoh, N., Shibuya, M. and Fukami, Y. : Genistein, a specific inhibitor of tyrosine- specific protein kinases. J. Biol. Chem. 262, 5592 (1987)
  9. Hollenberg, M. D. : Tyrosine kinase pathways and the regulation of smooth muscle contractility. Trends Pharmacol. Sci. 15, 108 (1994) https://doi.org/10.1016/0165-6147(94)90046-9
  10. Liu, C. Y. and Sturek, M. : Attenuation of endothelin-1-induced calcium response by tyrosine kinase inhibitors in vascular smooth muscle cells. Am. J. Physiol. 270, C1825 (1996) https://doi.org/10.1152/ajpcell.1996.270.6.C1825
  11. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994) https://doi.org/10.1038/372231a0
  12. Somlyo, A. P. and Somlyo, A. V. : From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta. Physiol. Scand. 164, 437 (1998) https://doi.org/10.1046/j.1365-201X.1998.00454.x
  13. Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T.,Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. : Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990-994 (1997) https://doi.org/10.1038/40187
  14. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. : Ca2+-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548 (2003) https://doi.org/10.1161/01.RES.0000090998.08629.60
  15. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994) https://doi.org/10.1038/372231a0
  16. Kitazawa, T., Masuo, M. and Somlyo, A. P. : Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc. Natl. Acad. Sci. USA 88, 9307 (1991)
  17. Gohla, A., Schultz, G. and Offermanns, S. : Roles for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction. Circ. Res. 87, 221 (2000) https://doi.org/10.1161/01.RES.87.3.221
  18. Leung, T., Manser, E., Tan, L. and Lim, L. : A novel serine/ threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J. Biol. Chem. 270, 29051 (1995) https://doi.org/10.1074/jbc.270.49.29051
  19. Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A. and Kaibuchi, K. : Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J. 15, 2208 (1996)
  20. Wilson, D. P., Susnjar, M., Kiss, E., Sutherland, C. and Walsh, M. P. : Thromboxane$ A_2$-induced contraction of rat caudal arteial smooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763 (2005).p https://doi.org/10.1042/BJ20050237
  21. Davis, M. J., Wu, X., Nurkiewicz, T. R., Kawasaki, J., Gui, P., Hill, M. A. and Wilson, E. : Regulation of ion channels by protein tyrosine phosphorylation. Am. J. Physiol. 281, H1835 (2001)
  22. Low, A. M. : Role of tyrosine kinase on $Ca^{2+}$ entry and refilling of agonist-sensitive $Ca^{2+}$ stores in vascular smooth muscles. Can. J. Physiol. Pharmacol. 74, 298 (1996) https://doi.org/10.1139/cjpp-74-3-298