Vazoactive Effects of Oxidative Stress Elicited by Hydrogen Peroxide in the Human Umbilical Artery: An in Vitro Study

DOI: 10.4236/pp.2011.24045   PDF   HTML     3,508 Downloads   6,844 Views   Citations


The vasoactive effects of oxidative stress induced by hydrogen peroxide (H2O2) on human umbilical artery strips as well as the possible mechanisms involved are studied. Contraction responses to cumulative H2O2 (10–7 M-3 × 10–2 M) in endothelium intact and denuded umbilical arteries and responses to cumulative H2O2 after incubation with L-NAME (10–4 M) (n = 8), indomethacin (10–5 M) (n = 8) and verapamil (10–6) (n = 8) were recorded. Responses elicited with cumulative H2O2 in Ca2+ free extracellular medium and the responses to cumulative Ca2+ (10–4 M-2 × 10–3 M) after H2O2 (10–3 M) induced contraction were also studied. The Emax for each experiment was calculated. p <0.05 was considered as significant. H2O2 elicited contraction was greater in endothelium denuded artery strips compared to endothelium intact strips (p < 0.05). Compared to control, incubation with L-NAME significantly augmented (p < 0.05), while verapamil and indomethacin inhibited the contractions elicited by cumulative H2O2 (p < 0.05). Ca2+ free extracellular medium caused decreases in cumulative H2O2 elicited contractions and cumulative Ca2+ caused concentration dependent increases in the contraction caused by a single bolus of H2O2 (p < 0.05). Exposure to H2O2 causes concentration-dependent constriction in human umbilical arteries. The presence of the endothelium and NOS enzyme activation influences the H2O2 responses. Removal of the endothelium increases the H2O2 elicited contractions more than incubation with L-NAME suggesting beside NO, other endothelial vasodilators are also involved in vascular tonus of the umbilical arteries. Both intracellular and extracellular Ca2+ ions and constrictor cyclooxygenase metabolites play a role in the contractile responses elicited by H2O2 in human umbilical arteries.

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I. Duman and N. Dogan, "Vazoactive Effects of Oxidative Stress Elicited by Hydrogen Peroxide in the Human Umbilical Artery: An in Vitro Study," Pharmacology & Pharmacy, Vol. 2 No. 4, 2011, pp. 347-353. doi: 10.4236/pp.2011.24045.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] T. Todros, A. Sciarrone, E. Piccoli, C. Guiot, P. Kaufmann and J. Kingdom, “Umbilical Doppler Waveforms and Placental Villous Angiogenesis in Pregnancies Complicated by Fetal Growth Restriction,” Obstet Gynecol, Vol. 93, No. 4, 1999, pp. 499-503.
[2] A. Fleischer, H. Schulman, G. Farmakides, L. Bracero, L. Grunfeld, B. Rochelson B and M. Koenigsberg, “Uterine artery Doppler Velocimetry in Pregnant Women with Hypertension,” Am J Obstet Gynecol, Vol. 154, No. 4, 1986, pp. 806-813.
[3] S. W. Leung, A. Quan, T. T Lao TT and R. Y. Man, Efficacy of Different Vasodilators on Human Umbilical Arterial Smooth Muscle under Normal and Reduced Oxygen Conditions. Early Hum Dev, Vol. 82, No 7, 2006, pp. 457-462.
[4] T. A. Mills, M. Wareing, A. A. H. Shennan, L. Poston, P. N. Baker and S. L. Greenwood, “Acute and Chronic Modulation of Placental Chorionic Plate Artery Reactivity by Reactive Oxygen Species,” Free Radic Biol Med, Vol. 47, No. 2, 2009, pp.159-166.
[5] N. Rani, R. Dhingra, D. S. Arya, M. Kalaivani, N. Bhatla and R. Kumar, “Role of Oxidative Stress Markers and Antioxidants in the Placenta of Preeclamptic Patients,” J Obstet Gynaecol Res, Vol. 36, No. 6, 2010, pp. 1189- 1194.
[6] A. Cinkaya, H. L. Keskin, U. Buyukkagnici, T. Gungor, E. A. Keskin, A. F. Avsar and U. Bilge. Maternal Plasma Total Antioxidant Status in Preterm Labor. J Obstet Gynaecol Res, Vol. 6, 2010, pp. 1185-1188.
[7] A. Negre-Salvayre, N. Auge, V. Ayala V, H. Basaga, J. Boada, R. Brenke, S. Chapple, G. Cohen, J. Feher, T. Grune, G. Lengyel, G. E. Mann, R. Pamplona, G. Poli, M. Portero-Otin, Y. Riahi, R. Salvayre, S. Sasson, J. Serrano, O. Shamni, W Siems, R. C. Siow, I. Wiswedel, K. Zarkovic and N. Zarkovic, “Pathological Aspects of Lipid Peroxidation,” Free Radic Res, Vol. 44, No. 10, 2010, pp. 1125-1171.
[8] T. Grune, N. Zarkovic and K. Kalliopi, “Lipid Peroxidation Sesearch in Europe and the COST B35 Action “Lipid Peroxidation Associated Disorders”, Free Radic Res, Vol. 44, No. 10, 2010, pp. 1095-1097.
[9] K. Matsubara, Y. Matsubara, S. Hyodo, T. Katayama and M. Ito, “Role of Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia. J Obstet Gynaecol Res, Vol. 36, No. 2, 2010, pp. 239-247.
[10] L. Carbillon, M. Uzan and S.Uzan, “Pregnancy, Vascular Tone, and Maternal Hemodynamics: a Crucial Adaptation,” Obstet Gynecol Survey, Vol. 55, No. 9, 2000, pp. 574-581.
[11] T. Matoba and H. Shimokawa, “Hydrogen Peroxide is an Endothelium-derived Hyperpolarizing Factor in Animals and Humans,” J Pharmacol Sci, 2003, Vol. 92, No. 1, pp. 1-6.
[12] K. Rytlewski, H. Huras, K. Kusmierska, A. Jaworowski, T. Gornisiewicz, P. Ossowski and A. Reron, “Doppler Velocimetry of the Materno-fetal Circulation in Preterm Delivered Pregnancies Complicated with Hypertension. Neuro Endocrinol Lett, Vol. 30, No. 3, 2009, pp. 403- 408.
[13] R. Cruz-Martinez and F. Figueras, “The Role of Doppler and Placental Screening. Best Pract Res Clin Obstet Gynaecol, Vol 23, No. 6, 2009, pp. 845-855.
[14] Y. Okatani, K. Watanabe and Y. Sagara, “Effect of Nitric Oxide, Prostacyclin and Tromboxane on the Vasospastic Action of Hydrogen Peroxide on Human Umbilical Artery,” Acta Obstet Gynecol Scand, Vol. 76, No. 6, 1997, pp. 515-520.
[15] Y. Okatani, K. Watanabe, A. Wakatsuki, S. Tamura and Y. Sagara, “Effects of Superoxide and Peroxynitrite on Vascular Tension in the Human Umbilical Artery,” Acta Obstet Gynecol Scand, Vol. 77, No. 9, 1998, pp. 883-888.
[16] N. Jin, C. S. Packer and R. A. Rhoades, “Reactive Oxygen-mediated Contraction in Pulmonary Arterial Smooth Muscle: Cellular Mechanisms. Can J Physiol Pharmacol, Vol. 69, No. 3, 1991, pp. 383-388.
[17] M. A. Rodríguez-Martínez, E. C. García-Cohen, A. B. Baena, R. González, M. Salaíces and J. Marín, “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.
[18] T. Hattori, J. Kajikuri, H. Katsuya and T. Itoh, “Effects of H2O2 on Membrane Potential of Smooth Muscle Cells in Rabbit Mesenteric Resistance Artery,” Eur J Pharmacol, Vol 464, No. 2-3, 2003, pp. 101-109.
[19] Y. J. Gao, S. Hirota, D. W. Zhang, L. J. Janssen and R. M. Lee, “Mechanisms of Hydrogen-peroxide-induced Bi- phasic Response in Rat Mesenteric Artery,” B J Pharmacol, Vol. 138, No. 6, 2003, pp. 1085-1092.
[20] S. Fujimoto, M. Mori and H. Tsushima, “Mechanisms Underlying the Hydrogen Peroxide-induced, Endothelium-independent Relaxation of the Norepinephrine- Contraction in Guinea-pig Aorta,” Eur J Pharmacol, Vol. 459, No. 1, 2003, pp. 65-73.
[21] R. S. Barlow, R. E. White, “Hydrogen Peroxide Relaxes Porcine Coronary Arteries by Stimulating BKCa Channel Activity,” Am J Physiol Heart Circ Physiol, Vol. 275, No. 4 pt 2, 1998, pp. H1283-H1289.
[22] R. Sotnikova, “Investigation of the Mechanisms Underlying H2O2-evoked Contraction in the Isolated Rat Aorta,” Gen Pharmacol, Vol. 31, No. 1, 1998, pp. 115- 119.
[23] G. Bodelsson and M. Stjernquist, “Endothelium-dependent Relaxation to Substance P in Human Umbilical Artery is Mediated via Prostanoid Synthesis,” Hum Reprod, Vol. 9, No. 4, 1994, pp. 733-737.
[24] W. Klockenbusch, H. Strobach H and K. Schr?r, “Any Physiological Role for Prostacyclin in Regulation of Fetal Vessel Tone? Agents Actions, Vol. 37, No. 1, 1992, pp. 361-368.
[25] D. W. Sheehan, E. C. Giese, Gugino SF, J. A. Russell, “Characterization and Mechanisms of H2O2-induced Contractions of Pulmonary Arteries,” Am J Physiol Heart Circ Physiol, Vol 264, No. 5 Pt 2, 1993, pp. H1542- H1547.
[26] 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.
[27] M. S. Wolin, C. A. Davidson, P. M. Kaminski, R. P. Fayngersh and K. M. Mohazzab-H, “Oxidant-Nitric Oxide Signalling Mechanisms in Vascular Tissue,” Biochemistry (Mosc), Vol. 63, No. 7, 1998, pp. 810-816.
[28] S. López-Ongil, G. Torrecillas, D. Pérez-Sala, L. González- Santiago, M. Rodríguez-Puyol and D. Rodríguez-Puyol, “Mechanisms Involved in the Contraction of Endothelial Cells by Hydrogen Peroxide,” Free Rad Biol Med, Vol. 26, No. 5-6, 1999, pp. 501-510.
[29] P. Srivastava, M. Rajanikanth, S. A. V. Raghavan and M. Dikshit, “Role of Endogenous Reactive Oxygen Derived Species and Cyclooxygenages Mediators in 5-hydroxy- tryptamine-induced Contractions in Rat Aorta: relationship to nitric oxide,” Pharmacol Res, Vol. 45, No. 5, 2002, 375-382.
[30] J. Daut, N. B. Standen and M. T. Nelson, “The Role of Membrane Potential of Endothelial and Smooth Muscle Cells in the Regulation of Coronary Blood Flow,” J Car- diovasc Electrophysiol, Vol. 5, No. 2, 1994, pp. 154-181.
[31] K. Bielefeldt, C. A. Whiteis, R. V. Sharma, F. M. Abboud and J. L. Conklin, “Reactive oxygen species and calcium homeostasis in cultured human intestinal smooth muscle cells,” Am J Physiol Heart Circ Physiol, Vol 272, No. 6 Pt 1, 1997, pp. G1439-1450.
[32] A. Roveri, M. Coassin, M. Maiorino, A. Zamburlini, F. T. van Amsterdam, E. Ratti and F. Ursini, “Effect of Hydrogen Peroxide on Calcium Homeostasis in Smooth Muscle Cells,” Arch Biochem Biophy, Vol 297, No. 2, 1992, pp. 265-270.
[33] W. Gen, M. Tani, J. Takeshita J, Y. Ebihara and K. Tamaki, “Mechanisms of Ca2+ Overload Induced by Extracellular H2O2 in Quiescent Isolated Rat Myocytes,” Basic Res Cardiol, Vol. 96, No. 6, 2001, pp. 623-629.
[34] J. Tang, J. H. Zhang, “Mechanisms of (Ca2+)i Elevation by H2O2 in Islets of Rats,” Life Sci, Vol. 68, No. 4, 2000, pp. 475-481.
[35] L. A. Blatter and W. G. Wier, “Nitric Oxide Decreased [Ca2+]i in Vascular Smooth Muscle by Inhibition of the Calcium Current,” Cell Calcium, Vol. 15, No. 2, 1994, pp. 122-131.
[36] D. Yang, M. Feletou, C. M. Boulanger, H. F. Wu, N. Levens, J. N. Zhang and P. M. Vanhoutte, “Oxygen-derived Free Radicals Mediate Endothelium-dependent Contractions to Acetylcholine in Aortas from Spontaneously Hypertensive Rats,” B J Pharmacol, Vol. 136, No. 1, 2002, pp. 104-110.

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