YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

The Synergistic Effect of Additional Ethanol Exposure on Quercetin-induced Vasorelaxation in a Vasoconstrictor-dependent Manner

Quercetin에 의한 혈관이완효과에 대한 알코올의 추가적인 역할

  • Jin, Young-Bae (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
  • 진영배 (대구가톨릭대학교 약학대학 약물학 교실) ;
  • 제현동 (대구가톨릭대학교 약학대학 약물학 교실)
  • Received : 2010.07.23
  • Accepted : 2010.09.29
  • Published : 2010.10.31
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Abstract

The aim of present study was to investigate the possible influence and related mechanism of additional alcohol on the flavonoid- induced arterial relaxation. 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 quercetin-induced relaxation cotreated with alcohol in rat aortae contracted with phorbol ester, fluoride or thromboxane $A_2$ mimetic U-46619. We hypothesized that cotreated alcohol plays a role in vascular relaxation evoked by quercetin 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. Quercetin inhibited phorbol ester, fluoride or thromboxane $A_2$-induced contraction regardless of endothelial function. However, alcohol didn't decrease any agonist-induced contraction. Interestingly, only in thromboxane $A_2$-induced contraction, synergistic results were observed in aortae denuded and cotreated with quercetin and alcohol suggesting that additional pathways different from antioxidation or endothelial nitric oxide synthesis might be involved in the vasorelaxation. In conclusion, in the agonists-contracted rat aortae, quercetin and alcohol together showed synergistic response regardless of endothelial function in an agonist-dependent manner.

Keywords

References

  1. Henriksson, K. M., Lindblad, U., Gullberg, B., Agren, B., Nilsson-Ehle, P. and Rastam, L. : Body composition, ethnicity and alcohol consumption as determinants for the development of blood pressure in a birth cohort of young middle-aged men. Eur. J. Epidemiol. 18(10), 955 (2003).
  2. Agarwal, D. P. and Srivastaba, L. M. : Does moderate alcohol intake protect against coronary heart disease? Indian Heart J. 53, 224 (2001).
  3. Agarwal, D. P. : Cardioprotective effects of light-moderate consumption of alcohol. a review of putative mechnism. Alcohol. Alcohol. 37, 409 (2002). https://doi.org/10.1093/alcalc/37.5.409
  4. Corrao, G., Rubbiati, L., Bagnardi, V., Zambon, A. and Poikolainen, K. : Alcohol and coronary heart disease. a meta analysis. Addiction 95, 1505 (2000). https://doi.org/10.1046/j.1360-0443.2000.951015056.x
  5. Toda, N. and Ayajiki, K. : Vascular actions of nitric oxide as affected by exposure to alcohol. Alcohol Alcohol. 45(4), 347 (2010). https://doi.org/10.1093/alcalc/agq028
  6. 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
  7. Moreira, A. J., Fraga, C., Alonso, M.,Collado, P. S., Zetller, C., Marroni, C., Marroni, N. and Gonzalez-Gallego, J. : Quercetin prevents oxidative stress and $NF-{\kappa}B$ activation in gastric mucosa of portal hypertensive rats. Biochem. Pharmacol. 68, 1939 (2004) https://doi.org/10.1016/j.bcp.2004.07.016
  8. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994). https://doi.org/10.1038/372231a0
  9. 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
  10. 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
  11. 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
  12. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994). https://doi.org/10.1038/372231a0
  13. 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
  14. 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
  15. 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
  16. 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).
  17. 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
  18. Je, H. D., Lee, M. H., Jeong, J. H., Park, S. Y. and Sohn, U. D. : Protective effect of resveratrol on agonist-dependent regulation of vascular contractility via inhibition of rho-kinase activity. Pharmacology 86(1), 37 (2010). https://doi.org/10.1159/000312665