YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

The Effect of Resveratrol on U-46619 (High Concentration)-induced Vasoconstriction Regulating MEK or Rho-kinase Activity

고농도 U-46619에 의한 혈관의 수축에 대한 Resveratrol의 억제 작용에서 MEK 활성 또는 Rho-kinase 활성의 변화: 내피 비의존적 수축성 조절

  • Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
  • 제현동 (대구가톨릭대학교 약학대학 약물학 교실)
  • Received : 2010.12.17
  • Accepted : 2011.03.07
  • Published : 2011.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

The aim of present study was to investigate the possible influence and related mechanism of resveratrol on U-46619 (high concentration)-induced vasoconstriction. Agonist-induced vascular smooth muscle contractions involve the activation of thick or thin filament pathway. However, there are no reports addressing the question whether this pathway is involved in resveratrol-induced relaxation in rat aortae contracted with high U-46619. We hypothesized that MEK or Rho-kinase inhibition plays a role in vascular relaxation evoked by resveratrol in rat aortae. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Resveratrol fully inhibited U-46619 in low concentration-induced contraction regardless of endothelial function. However, resveratrol partially decreased U-46619 in high concentration-induced contraction regardless of endothelial function. Interestingly, only in U-46619 (high concentration)-induced contraction, no significant decrease was observed in phospho-ERK1/2 levels and slight decrease in phospho-MYPT1 levels suggesting that additional pathways different from them or endothelial nitric oxide synthesis might be involved in the vasorelaxation. In conclusion, in high U-46619-contracted rat aortae, resveratrol showed relaxation response regardless of endothelial function significantly but slightly decreasing MYPT1 phosphorylation rather than ERK1/2 phosphorylation.

Keywords

References

  1. Benavente-Garcia, O., Castillo, J., Marin, F. R., Ortuno, A. and Del-Rio, J. A. : J. Agri. Food Chem. 45, 4505 (1997). https://doi.org/10.1021/jf970373s
  2. Hain, R., Bieseler, B., Kindl, H., Schroder, G. and Stocker, R. : Expression of a stilbene synthase gene in Nicotiana tabacum results in synthesis of the phytoalexin resveratrol. Plant Mol. Biol. 15, 325 (1990). https://doi.org/10.1007/BF00036918
  3. Hain, R., Rief, H. J., Krause, E., Langebartels, R., Kindl, H., Vornam, B., Wiese, W., Schmelzer, E., Schreier, P. H., Stocker, R. H. and Stenzel, K. : Disease resistance results from foreign phytoalexin expression in a novel plant. Nature 361, 153 (1993). https://doi.org/10.1038/361153a0
  4. Bhat, K. P. L. and Pezzuto, J. M. : Cancer chemopreventive activity of resveratrol. Ann. N.Y. Acad. Sci. 957, 210 (2002). https://doi.org/10.1111/j.1749-6632.2002.tb02918.x
  5. Pervaiz, S. : Resveratrol: From grapevines to mammalian biology. FASEB J. 17, 1975 (2003). https://doi.org/10.1096/fj.03-0168rev
  6. Kopp, P. : Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'? Eur. J. Endocrinol. 138, 619 (1998). https://doi.org/10.1530/eje.0.1380619
  7. Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L. L., Scherer, B. and Sinclair, D. A. : Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425, 191 (2003). https://doi.org/10.1038/nature01960
  8. Bhat, K. P. and Pezzuto, J. M. : Cancer chemopreventive activity of resveratrol. Ann. N.Y. Acad. Sci. 957, 210 (2002). https://doi.org/10.1111/j.1749-6632.2002.tb02918.x
  9. Martinez, J. and Moreno, J. J. : Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem. Pharmacol. 59, 865 (2000). https://doi.org/10.1016/S0006-2952(99)00380-9
  10. Subbaramaiah, K., Chung, W. J., Michaluart, P., Telang, N., Tanabe, T., Inoue, H., Jang, M., Pezzuto, J. M. and Dannenberg, A. J. : Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester- treated human mammary epithelial cells. J. Biol. Chem. 273, 21875 (1998). https://doi.org/10.1074/jbc.273.34.21875
  11. Tsai, S. H., Lin-Shiau, S. Y. and Lin, J. K. : Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Brit. J. Pharmacol. 126, 673 (1999). https://doi.org/10.1038/sj.bjp.0702357
  12. Wadsworth, T. L. and Koop, D. R. : Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem. Pharmacol. 57, 941 (1999). https://doi.org/10.1016/S0006-2952(99)00002-7
  13. Chan, M. M., Mattiacci, J. A., Hwang, H. S., Shah, A. and Fong, D. : Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem. Pharmacol. 60, 1539 (2000). https://doi.org/10.1016/S0006-2952(00)00471-8
  14. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994). https://doi.org/10.1038/372231a0
  15. 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
  16. 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 (1997). https://doi.org/10.1038/40187
  17. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. : $Ca^{2+}$-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
  18. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994). https://doi.org/10.1038/372231a0
  19. 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). https://doi.org/10.1073/pnas.88.20.9307
  20. 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
  21. 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
  22. 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).
  23. 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). https://doi.org/10.1042/BJ20050237
  24. Song, S. H., Min, H. Y. and Lee, S. K. : Suppression of prostaglandin E2-mediated cell proliferation and signal transduction by resveratrol in human colon cancer cells. Biomol. Ther. 18, 402 (2010). https://doi.org/10.4062/biomolther.2010.18.4.402