Abstract
Resveratrol, a natural phytoalexin found in wine, has been suggested to have benefits in preventing cardiovascular diseases. However, the direct effects of resveratrol on the activity of cardiac tissues and its mechanism of action have not been determined. This study examined the effects of resveratrol on the right and left atrium and left papillary muscle isolated from the rat heart. The contractile responses of the right atrium and papillary muscle and the action potential from the left atrium were recorded and the effects of resveratrol on these responses were observed. The resting force of the isolated right atrium and the peak developed force of the left papillary muscle were depressed by resveratrol (0.1 nM – 0.1 mM). Exposure to the KATP channel blocker glyburide (3 μM) prevented significantly the resveratrol-induced decrease. Resveratrol (0.1 mM) shortened the repolarization phase of action potential recorded from the left atrium and this effect of resveratrol was reversed by glyburide (3 μM). These results indicated that resveratrol depressed cardiac muscle contraction and shortened action potential duration probably due to the activation of KATP channels in the rat heart.
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Baker, J. E., Contney, S. J., Singh, R., Kalyanaraman, B., Gross, G. J., and Bosnjak, Z. J., Nitric oxide activates the sarcolemmal KATP channel in normoxic and chronically hypoxic heart by a cyclic GMP-dependent mechanism.J. Mol. Cell Cardiol., 33, 331–341 (2001).
Bradamante, S., Barenghi, L., Piccinini, F., Bertelli, A.A.E., De Jonge, R., Beemster, P., and De Jong, J.W., Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism.Eur. J. Pharmacol., 465, 115–123 (2003).
Brady, A. J., Warren, J. B., Poole-Wilson, P. A., Williams, T. J., and Harding, S. E., Nitric oxide attenuates cardiac myocyte contraction.Am. J. Physiol., 265, H176-H182 (1993).
Buluc, M. and Demirel-Yilmaz, E., Possible mechanism for depression of smooth muscle tone by resveratrol. In: Adv. Rec. Cardiovas. Res. Ed.: A. Varro, A. Vegh. Monduzzi Editore, Bologna, Italy, pp. 55–59, (2002).
Buluc, M. and Demirel-Yilmaz, E., Resveratrol decreases calcium sensitivity of vascular smooth muscle and enhances cytosolic calcium increase in endothelium.Vas. Pharmacol., 44(4), 231–237(2006).
Chen, C. C., Lin, Y. C., Chen, S. A., Luk, H. N., Ding, P. Y. A., Chang, M. S., and Chiang, C. E., Shortening of cardiac action potentials in endotoxic shock in guinea pigs is caused by an increase in nitric oxide activity and activation of the adenosine triphosphate-sensitive potassium channel.Crit. Care Med., 28, 1713–1720 (2000).
Chen, C. K. and Pace-Asciak, C. R., Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta.Gen. Pharmacol., 27, 363–366 (1996).
Das, D. K., Sato, M., Ray, P. S., Maulik, G., Engelman, R. M., Bertelli, A. A., and Bertelli, A., Cardioprotection of red wine: role of polyphenolic antioxidants.Drugs Exp. Clin. Res., 25, 115–120 (1999).
El-Mowafy, A. M., Resveratrol activates membrane-bound guanylyl cyclase in coronary arterial smooth muscle: A novel signaling mechanism in support of coronary protection.Biochem. Biophys. Res. Commun., 291, 1218–1224 (2002).
Fremont, L., Biological effects of resveratrol.Life Sci., 66, 663–673 (2000).
German, J. B. and Walzern, R. L., The health benefits of wine.Annu. Rev. Nutr., 20, 561–593 (2000).
Han, J., Kim, N., Joo, H., Kim, E., and Earm, Y. E., ATP- sensitive K+ channels activation by nitric oxide and protein kinase G in rabbit ventricular myocytes.Am. J. Physiol., 283, H1545-H1554 (2002).
Hertog, M. G. L., Feskens, E. J. M., Hollman, P. C. H., Katan, M. B., and Kromhout, D., Dietary antioxidant flavonoids and risk of coronary heart disease.The Zutphen Elderly Study.Lancet, 342, 1007–1011 (1993).
Hung, L. M., Su, M. J., and Chen, J. K., Resveratrol protects myocardial ischemia-reperfusion injury through both NO- dependent and NO-independent mechanisms.Free Radic. Biol. Med., 36, 774–778 (2004).
Jager, U. and Nguyen-Duong, H., Relaxant effect of trans-resveratrol on isolated porcine coronary arteries.Arzneim. Forsch., 49, 207–211 (1999).
Liew, R., Stagg, M. A., MacLeod, K. T., and Collins, P., The red wine phenol, resveratrol, exerts acute direct action on guinea-pig ventricular myocytes.Eur. J. Pharmacol., 519, 1–8 (2005).
Martin, S., Andriambeloson, E., Takeda, K., and Andriantsitohaina, R., Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signaling pathways leading to nitric oxide production.Br. J. Pharmacol., 135, 1579–1587 (2002).
Naderali, E. K., Doyle, P. J., and Williams, G., Resveratrol induces vasorelaxation of mesenteric and uterine arteries from female guinea pigs.Clin. Sci., 98, 537–543 (2000).
Nichols, C. G., Ripol, C., and Lederer, W. J., ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction.Circ. Res., 68, 280–287 (1991).
Orallo, F., Alvarez, E., Camina, M., Leiro, J. M., Gomez, E., and Fernandez, R., The possible implication of resveratrol in the cardioprotective effects of long-term moderate wine consumption.Mol. Pharmacol., 61, 294–302 (2002).
Ray, P. S., Maulik, G., Cordis, G. A., Bertelli, A. A., Bertelli, A., and Das, D. K., The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury.Free Radic. Biol. Med., 27, 160–169 (1999).
Sato, M., Ray, P. S., Meulki, G., Meulki, N., Engelman, R. M., Bertelli, A. A. E., and Das, D. K., Myocardial protection with red wine extract.J. Cardiovas. Pharmacol., 35, 263–268 (2000).
Schlossmann, J., Feil, R., and Hofmann, F., Signaling through NO and cGMP-dependent protein kinases.Ann. Med., 35, 21–27 (2003).
Soleas, G. J., Diamandis, E., and Goldberg, D. M., Resveratrol: a molecule whose time has come? and gone?Clin. Biochem., 30, 91–113 (1997).
Wahler, G. M. and Sperelakis, N., Intracellular injection of cyclic GMP depresses cardiac slow action potentials.J. Cyclic Nucleotid Protein Phosphor. Res., 10, 83–95 (1985).
Zhao, J., Ma, H. J., Dong, J. H., Zhang, L. P., Liu, H. L., and Wang, Q. S., Electrophysilogical effects of resveratrol on guinea pig papillary muscles.Acta Physiol. Sin., 56, 708–712 2004).
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Buluc, M., Ayaz, M., Turan, B. et al. Resveratrol-induced depression of the mechanical and electrical activities of the rat heart is reversed by glyburide: evidence for possible KATP channels activation. Arch Pharm Res 30, 603–607 (2007). https://doi.org/10.1007/BF02977655
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DOI: https://doi.org/10.1007/BF02977655