Effects of Levosimendan on Hydrogen Peroxide Induced Contraction in Human Saphenous Vein
Burak Cem Soner, Ayse Saide Sahin, Ipek Duman, Niyazi Gormus
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DOI: 10.4236/pp.2011.24030   PDF    HTML     4,373 Downloads   8,705 Views   Citations

Abstract

Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H2O2 in human saphenous vein (HSV) segments. Methods: We studied H2O2 induced contractions of isolated HSV mounted in standard tissue baths. H2O2 (10-6 – 10-3 M) was added cumulatively to the organ bath. Concentration-response curves to H2O2 were repeated in the presence of levosimendan (10–8 M). In the second series of experiments, strips were contracted with 5-HT (10–5 M). When the contraction reached a stable plateau, H2O2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H2O2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H2O2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H2O2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.

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B. Soner, A. Sahin, I. Duman and N. Gormus, "Effects of Levosimendan on Hydrogen Peroxide Induced Contraction in Human Saphenous Vein," Pharmacology & Pharmacy, Vol. 2 No. 4, 2011, pp. 233-237. doi: 10.4236/pp.2011.24030.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] E. Nakamura, N. Tanaka N, M. Kuwabara M, A. Yamashita, Y. Matsuo, T. Kanai, T. Onitsuka, Y. Asada, H. Hisa and R. Yamamoto, “Relative contributions of 5-hydroxytryptamine (5-HT) receptor subtypes in 5-HT-induced vasoconstriction of the distended human saphenous vein as a coronary artery bypass graft,” Biol Pharm Bull, Vol. 34, No. 1, 2011, pp. 82-86.
[2] C. A. Hamilton, G. O’Dowd, L. McIntosh, G. Berg, J. Butler, V. Pathi, R. Williams, J.L. Reid and A.F. Dominiczak, “Vasorelaxant properties of isolated human radial arteries: comparison with internal mammary arteries,” Atherosclerosis, Vol. 160, No. 2, 2002, pp. 345-353.
[3] S. Attaran, L. John and A. El-Gamel, “Clinical and potential use of pharmacological agents to reduce radial artery spasm in coronary artery surgery,” Ann Thorac Surg, Vol. 85, No. 4, 2008, pp. 1483-1489.
[4] J.T. Parissis, I. Andreadou, S.L. Markantonis, V. Bistola, A. Louka, A. Pyriochou, I. Paraskevaidis, G. Filippatos, E.K. Iliodromitis and D.T. Kremastinos, “Effects of levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure,” Atherosclerosis, Vol. 195, No. 2, 2007, 210-215.
[5] K.H. Konz, M. Haap, K.E. Hill, R.F. Burk and R.A. Walsh, “Diastolic dysfunction of perfused rat hearts induced by hydrogen peroxide. Protective effect of selenium,” J Mol Cell Cardiol, Vol. 21, No. 8, 1989, pp. 789- 795.
[6] M.A. Rodriguez-Martinez, E.C. Garcia-Cohen, A.B. Baena, R. Gonzalez, M. Salaices and J. Marin, “Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved,” Br J Pharmacol, Vol. 125, No. 6, 1998, pp.1329-1335.
[7] Z.W. Yang, T. Zheng, A. Zhang, B.T. Altura and B.M. Altura, “Mechanisms of hydrogen peroxide-induced contraction of rat aorta,” Eur J Phrmacol, Vol. 344, No. 2-3, 1998, pp. 169-181.
[8] A.S. Sahin, E.A. Atalik, T.K. Sahin and N Do?an, “Cooling and response to hydrogen peroxide in human saphenous vein: role of the endothelium.,” Fundam Clin Pharmacol, Vol. 19, No. 3, 2005, pp.341-346
[9] K. Watanabe, Y. Okatani and Y. Sagara, “Potentiating effect of hydrogen peroxide on the serotonin-induced vasocontraction in human umbilical artery,” Acta Obstet Gynecol Scand, Vol. 75, No. 9, 1996, pp. 783-789.
[10] J.T. Parissis, I. Andreadou, V. Bistola, I. Paraskevaidis, G. Filippatos and D.T. Kremastinos, “Novel biologic mechanisms of levosimendan and its effect on the failing heart,” Expert Opin Investig Drugs, Vol. 17, No. 8, 2008, pp. 1143-1150.
[11] R.S. Barlow, A.M. El-Mowafy, RE and White, “H2O2 opens BKca channels via the PLA2-arachidonic acid signaling cascade in coronary artery smooth muscle,” Am J Physiol Heart Circ Physiol, Vol 279, No. 2, 2000, pp. H475-483.
[12] T. Suvorava, N. Lauer, S. Kumpf, R. Jacob, W. Meyer and G. Kojda, “Endogenous vascular hydrogen peroxide regulates arteriolar tension in vivo” Circulation, Vol. 112, No. 16, 2005, pp. 2487-2495.
[13] A. Hara, T. Suzuki, H. Hashizume, N. Shishido, M. Nakamura, F. Ushikubi and Y. Abiko, “Effects of CP-060S, a novel Ca2+ channel blocker, on oxidative stress in cultured cardiac myocytes,” Eur J Pharmacol, Vol. 385, No. 1, 1999, pp. 81-88.
[14] S. Shimizu, Y. Saitoh, T. Yamamoto and K. Momose, “Stimulation by hydrogen peroxide of L-arginine metabolism to L-citrulline coupled with nitric oxide synthesis in cultured endothelial cells,” Res Commun Chem Pathol Pharmacol, Vol. 84, No. 3, 1994, pp. 315-329.
[15] Z.W. Yang, T. Zheng, J. Wang, A. Zhang, B.T. Altura and B.M. Altura, “Hydrogen peroxide induces contraction and raises [Ca2+] i in canine cerebral arterial smooth muscle: participation of cellular signaling pathways,” Naunyn Schmiedebergs Arc Pharmacol, Vol. 360, No. 6, 1999, pp. 646-653.
[16] H. Mirkhani, M. Shafa and H. Khazraei, “Comparison of the effects of levosimendan and papaverine on human internal mammary artery and saphenous vein,” Cardiovasc Drugs Ther, Vol. 23, No. 5, 2009, pp. 355-359.
[17] E.P. Sandell, M. Hayha, S. Antila, P. Heikkinen, P Ottoila, L.A. Lehtonen and P.J. Pentikainen, “Pharmacokinetics of levosimendan in healthy volunteers and patients with congestive heart failure,” J Cardiovasc Pharmacol, Vol. 26, No. Supl 1, 1995, pp. 557-562.
[18] G. Lilleberg, S. Sundberg and M.S. Nieminen, “Dose- range study of a new calcium sensitizier, levosimendan, in patients with left ventricular dysfunction,” J Cardiovasc Pharmacol, Vol. 26, No. Suppl. 1, 1995, pp. S563- 569.
[19] O. Pollesello and Z. Papp, “The cardioprotective effects of levosimendan: preclinical and clinical evidence,” J Cardiovasc Pharmacol, Vol. 50, No. 3, 2007, pp. 257- 263.
[20] C. Avgeropoulou, I. Andreadou, S. Markantonis-Ky- roudis, M. Demopoulou, P Missovoulos, A. Androulakis and I. Kallikazaros, “The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine,” Eur J Heart Fail, Vol. 7, No. 5, 2005, pp. 882-887.
[21] D.M. Kopustinskiene, P. Pollesello, N.E. Saris, “Levosi- mendan is a mitochondrial K(ATP) channel opener, “Eur J Pharmacol, Vol. 428, No. 3, 2001, pp. 311-314.
[22] A.S. Sahin, N. Gormus and A. Duman, “Preconditioning with levosimendan prevents contractile dysfunction due to H2O2-induced oxidative stress in human myocardium” J Cardiovasc Pharmacol, Vol. 50, No. 4, 2007, pp. 419- 423.
[23] J. Pataricza, J. Szolnoky, I. Krassoi, Z. Hegedus, A. Kun, A. Varro and J.G. Papp, “Vazorelaxing effect of levosi- mendan against 5-hydroxytryptamine-induced contractions in isolated human conduit bypass grafts,” J Pharm Pharmacol, Vol 58, No. 8, 2006, pp. 1107-1112.
[24] J. Hohn, J. Pataricza A. Petri, “Levosimendan interacts with potassium channel blockers in human saphenous veins,” Basic Clin Pharmacol Toxicol, Vol. 94, No. 6, 2004, pp. 271-273.

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