Browse > Article
http://dx.doi.org/10.4062/biomolther.2017.197

Endothelium Independent Effect of Pelargonidin on Vasoconstriction in Rat Aorta  

Min, Young Sil (Department of Medical Plant Science, College of Scienceand Engineering, Jung Won University)
Yoon, Hyuk-Jun (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Lee, Jong Hyuk (Department of Pharmaceutical Engineering, College of Life and Health Science, Hoseo University)
Yoo, Seong Su (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
Shim, Hyun Sub (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
Lee, Hak Yeong (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
La, Hyen-Oh (Department of Clinical Pharmacology, College of Pharmacy, Catholic University of Korea)
Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.26, no.4, 2018 , pp. 374-379 More about this Journal
Abstract
In this study, we investigated the effects of pelargonidin, an anthocyanidin found in many fruits and vegetables, on endothelium-independent vascular contractility to determine the underlying mechanism of relaxation. Isometric contractions of denuded aortic muscles from male rats were recorded, and the data were combined with those obtained in western blot analysis. Pelargonidin significantly inhibited fluoride-, thromboxane A2-, and phorbol ester-induced vascular contractions, regardless of the presence or absence of endothelium, suggesting a direct effect of the compound on vascular smooth muscles via a different pathway. Pelargonidin significantly inhibited the fluoride-dependent increase in the level of myosin phosphatase target subunit 1 (MYPT1) phosphorylation at Thr-855 and the phorbol 12,13-dibutyrate-dependent increase in the level of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at Thr202/Tyr204, suggesting the inhibition of Rho-kinase and mitogen-activated protein kinase kinase (MEK) activities and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxation effect of pelargonidin on agonist-dependent vascular contractions includes inhibition of Rho-kinase and MEK activities, independent of the endothelial function.
Keywords
ERK1/2; Fluoride; MYPT1; Pelargonidin; Phorbol ester; Rho-kinase;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 Son, J. E., Jeong, H., Kim, H., Kim, Y. A., Lee, E., Lee, H. J. and Lee, K. W. (2014) Pelargonidin attenuates PDGF-BB-induced aortic smooth muscle cell proliferation and migration by direct inhibition of focal adhesion kinase. Biochem. Pharmacol. 89, 236-245.   DOI
2 Taubert, D., Berkels, R., Klaus, W. and Roesen, R. (2002) Nitric oxide formation and corresponding relaxation of porcine coronary arteries induced by plant phenols: essential structural features. J. Cardiovasc. Pharmacol. 40, 701-713.   DOI
3 Tsai, M. H. and Jiang, M. J. (2006) Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers Arch. 453, 223-232.   DOI
4 Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. (1997) Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990-994.   DOI
5 Wier, W. G. and Morgan, K. G. (2003) Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. Rev. Physiol. Biochem. Pharmacol. 150, 91-139.
6 Wilson, D. P., Susnjar, M., Kiss, E., Sutherland, C. and Walsh, M. P. (2005) Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763-774.   DOI
7 Wooldridge, A. A., MacDonald, J. A., Erdodi, F., Ma, C., Borman, M. A., Hartshorne, D. J. and Haystead, T. A. (2004) Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J. Biol. Chem. 279, 34496-34504.   DOI
8 Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y. and Kaibuchi, K. (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase) J. Biol. Chem. 271, 20246-20249.   DOI
9 Ajay, M., Gilani, A. U. and Mustafa, M. R. (2003) Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci. 74, 603-612.   DOI
10 Akata, T. (2007) Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in vascular smooth muscle cells. J. Anesth. 21, 232-242.   DOI
11 Appel, L. J., Brands, M. W., Daniels, S. R., Karanja, N., Elmer, P. J. and Sacks, F. M. (2006) Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension 47, 296-308.   DOI
12 Brietz, A., Schuch, K. V., Wangorsch, G., Lorenz, K. and Dandekar, T. (2016) Analyzing ERK 1/2 signalling and targets. Mol. Biosyst. 12, 2436-2446.   DOI
13 Castaneda-Ovando, A., de Lourdes Pacheco-Hernandez, M., Paez-Hernandez, M. E., Rodriguez, J. A. and Galan-Vidal, C. A. (2009) Chemical studies of anthocyanins: a review. Food Chem. 113, 859-871.   DOI
14 Choi, S., Kim, J. A., Kim, K. C. and Suh, S. H. (2015) Isolation and in vitro culture of vascular endothelial cells from mice. Korean J. Physiol. Pharmacol. 19, 35-42.   DOI
15 Choi, S., Kwon, H. J., Song, H. J., Choi, S. W., Nagar, H., Piao, S., Jung, S. B., Jeon, B. H., Kim, D. W. and Kim, C. S. (2016) Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway. Korean J. Physiol. Pharmacol. 20, 539-545.   DOI
16 Hamalainen, M., Nieminen, R., Vuorela, P., Heinonen, M. and Moilanen, E. (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007, 45673.
17 Zou, Q., Leung, S. W. and Vanhoutte, P. M. (2015) Transient receptor potential channel opening releases endogenous acetylcholine, which contributes to endothelium-dependent relaxation induced by mild hypothermia in spontaneously hypertensive rat but not wistarkyoto rat arteries. J. Pharmacol. Exp. Ther. 354, 121-130.   DOI
18 Gallet, C., Blaie, S., Levy-Toledano, S. and Habib, A. (2003) Thromboxane-induced ERK phosphorylation in human aortic smooth muscle cells. Adv. Exp. Med. Biol. 525, 71-73.
19 Goyal, R., Mittal, A., Chu, N., Shi, L., Zhang, L. and Longo, L. D. (2009) Maturation and the role of PKC-mediated contractility in ovine cerebral arteries. Am. J. Physiol. Heart Circ. Physiol. 297, H2242-H2252.   DOI
20 Gu, Z., Kordowska, J., Williams, G. L., Wang, C. L. and Hai, C. M. (2007) Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells. Exp. Cell Res. 313, 849-866.   DOI
21 He, J. and Giusti, M. M. (2010) Anthocyanins: natural colorants with health-promoting properties. Annu. Rev. Food Sci. Technol. 1, 163-187.   DOI
22 Je, H. D. and Sohn, U. D. (2009) Inhibitory effect of genistein on agonist-induced modulation of vascular contractility. Mol. Cells 27, 191-198.   DOI
23 Jeon, S. B., Jin, F., Kim, J. I., Kim, S. H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H. and Kim, I. K. (2006) A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem. Biophys. Res. Commun. 343, 27-33.   DOI
24 Kim, J. G., Sung, H. J., Ok, S. H., Kwon, S. C., Cheon, K. S., Kim, H. J., Chang, K. C., Shin, I. W., Lee, H. K., Chung, Y. K. and Sohn, J. T. (2011) Calcium sensitization involved in dexmedetomidine-induced contraction of isolated rat aorta. Can. J. Physiol. Pharmacol. 89, 681-689.   DOI
25 Pfitzer, G. (2001) Invited review: regulation of myosin phosphorylation in smooth muscle. J. Appl. Physiol. 91, 497-503.   DOI
26 Noda, Y., Kaneyuki, T., Mori, A. and Packer, L. (2002) Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin. J. Agric. Food Chem. 50, 166-171.   DOI
27 Nong, L., Ma, J., Zhang, G., Deng, C., Mao, S., Li, H. and Cui, J. (2016) Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase. Korean J. Physiol. Pharmacol. 20, 441-447.   DOI
28 Ouanouki, A., Lamy, S. and Annabi, B. (2017) Anthocyanidins inhibit epithelial-mesenchymal transition through a TGFbeta/Smad2 signaling pathway in glioblastoma cells. Mol. Carcinog. 56, 1088-1099.   DOI
29 Roy, M., Sen, S. and Chakraborti, A. S. (2008) Action of pelargonidin on hyperglycemia and oxidative damage in diabetic rats: implication for glycation-induced hemoglobin modification. Life Sci. 82, 1102-1110.   DOI
30 Ruppert, C., Deiss, K., Herrmann, S., Vidal, M., Oezkur, M., Gorski, A., Weidemann, F., Lohse, M. J. and Lorenz, K. (2013) Interference with ERK(Thr188) phosphorylation impairs pathological but not physiological cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A. 110, 7440-7445.   DOI
31 Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. (2003) Ca2+-dependent activation of Rho and Rho kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548-556.   DOI
32 Somlyo, A. P. and Somlyo, A. V. (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 83, 1325-1358.   DOI