Skip to main content
Log in

Oxidative stress promotes blood cell-endothelial cell interactions in the microcirculation

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the capacity of the cell to detoxify these potentially injurious oxidants using endogenous antioxidant defense systems. Conditions associated with oxidative stress include ischemia/reperfusion, hypercholesterolemia, diabetes, and hypertension. The adhesion of circulating blood cells (leukocytes, platelets) to vascular endothelium is a key element of the pro-inflammatory and prothrombogenic phenotype assumed by the vasculature in these and other disease states that are associated with an oxidative stress. There is a growing body of evidence that links the blood cell-endothelial cell interactions in these conditions to the enhanced production of ROS. Potential enzymatic sources of ROS within the microcirculation include xanthine oxidase, NAD(P)H oxidase, and nitric oxide synthase. ROS can promote a pro-inflammatory/prothrombogenic phenotype within the microvasculature by a variety of mechanisms, including the inactivation of nitric oxide, the activation of redox-sensitive transcription factors (e.g., nuclear factor-ξB) that govern the expression of endothelial cell adhesion molecules (e.g., P-selectin), and the activation of enzymes (e.g., phospholipase A2) that produce leukocyte-stimulating inflammatory mediators (e.g., platelet-activating factor). The extensively documented ability of different oxidant-ablating interventions to attenuate blood cell-endothelial cell interactions underscores the importance of ROS in mediating the dysfunctional microvascular responses to oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Eppihimer, M.J. and Granger, D.N. (1997). Ischemia/reperfusion-induced leukocyte-endothelial interactions in postcapillary venules. Shock. 8:16–25.

    Article  PubMed  CAS  Google Scholar 

  2. Salter, J.W., Krieglstein, C.F., Issekutz, A.C., and Granger, D.N. (2001). Platelets modulate ischemia/reperfusion-induced leukocyte recruitment in the mesenteric circulation. Am. J. Physiol. Gastrointest. Liver Physiol.. 281:G1432-G1439.

    PubMed  CAS  Google Scholar 

  3. Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J., and Jones, H.P. (1987). Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest.. 79:1564–1570.

    PubMed  CAS  Google Scholar 

  4. Im, M.J. Hoopes, J.E., Yoshimura, Y., Manson, P.N., and Bulkley, G.B. (1989), Xanthine: acceptor oxidoreductase activities in ischemic rat skin flaps. J. Surg. Res.. 46:230–234.

    Article  PubMed  CAS  Google Scholar 

  5. Granger, D.N., Benoit, J.N., Suzuki, M., and Grisham, M.B. (1989). Leukocyte adherence to venular endothelium during ischemia-reperfusion. Am. J. Physiol.. 257:G683-G688.

    PubMed  CAS  Google Scholar 

  6. Kurose, I., Argenbright, L.W., Wolf, R., Lianxi, L., and Granger, D.N. (1997). Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators. Am. J. Physiol.. 272:H2976-H2982.

    PubMed  CAS  Google Scholar 

  7. Gaboury, J.P., Anderson, D.C., and Kubes, P. (1994). Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo. Am. J. Physiol. 266:H637-H642.

    PubMed  CAS  Google Scholar 

  8. Cai, H. and Harrison, D.G. (2000): Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ. Res.. 87:840–844.

    PubMed  CAS  Google Scholar 

  9. Desco, M.C., Asensi, M., Marquez, R., et al. (2002). Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes. 51:1118–1124.

    Article  PubMed  CAS  Google Scholar 

  10. Griendling, K.K., Sorescu, D., and Ushio-Fukai, M. (2000). NAD(P)H oxidase: role in cardiovascular biology and disease. Circ. Res. 86:494–501.

    PubMed  CAS  Google Scholar 

  11. Jones, S.A., O’Donnell, V.B., Wood, J.D., Broughton, J.P., Hughes, E.J., and Jones, O.T. (1996). Expression of phagocyte NADPH oxidase components in human endothelial cells. Am. J. Physiol. 271:H1626-H1634.

    PubMed  CAS  Google Scholar 

  12. Seno, T., Inoue, N., Gao, D., et al. (2001). Involvement of NADH/NADPH oxidase in human platelet ROS production. Thromb. Res. 103:399–409.

    Article  PubMed  CAS  Google Scholar 

  13. Babior, B.M. (2002). The neutrophil NADPH oxidase. Arch. Biochem. Biophys. 397:342–344.

    Article  PubMed  CAS  Google Scholar 

  14. Li, J.M., Mullen, A.M., Yun, S., et al. (2002). Essential role of the NADPH oxidase subunit p47(phox) in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-alpha. Circ. Res. 90:143–150.

    Article  PubMed  CAS  Google Scholar 

  15. Stokes, K.Y., Clanton, E.C., Russell, J.M., Ross, C.R., and Granger, D.N. (2001). NAD(P)H oxidase-derived superoxide mediates hypercholesterolemia-induced leukocyte-endothelial cell adhesion. Circ. Res. 88:499–505.

    PubMed  CAS  Google Scholar 

  16. Guzik, T.J., Mussa, S., Gastaldi, D., et al. (2002). Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105:1656–1662.

    Article  PubMed  CAS  Google Scholar 

  17. Kerr, S., Brosnan, M.J., McIntyre, M., Reid, J.L., Dominiczak, A.F., and Hamilton, C.A. (1999). Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium. Hypertension 33:1353–1358.

    PubMed  CAS  Google Scholar 

  18. Creager, M.A., Gallagher, S.J., Girerd, X.J., Coleman, S.M., Dzau, V.J., and Cooke, J.P. (1992). l-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin. Invest. 90:1248–1253.

    PubMed  CAS  Google Scholar 

  19. Katusic, Z.S. (2001). Vascular endothelial dysfunction: does tetrahydrobiopterin play a role? Am. J. Physiol. Heart Circ. Physiol. 281:H981-H986.

    PubMed  CAS  Google Scholar 

  20. Stroes, E., Kastelein, J., Cosentino, F., et al. (1997). Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J. Clin. Invest. 99:41–46.

    PubMed  CAS  Google Scholar 

  21. Vasquez-Vivar, J., Martasek, P., Whitsett, J., Joseph, J., and Kalyanaraman, B. (2002) The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study. Biochem. J. 362: 723–739.

    Article  Google Scholar 

  22. Laursen, J.B., Somers, M., Kurz, S., et al. (2001). Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 103:1282–1288.

    PubMed  CAS  Google Scholar 

  23. Hong, H.J., Hsiao, G., Cheng, T.H., and Yen, M.H. (2001). Supplemention with tetrahydrobiopterin suppresses the development of hypertension in spontaneously hypertensive rats. Hypertension 38:1044–1048.

    PubMed  CAS  Google Scholar 

  24. Zimmerman, B.J., Grisham, M.B., and Granger, D.N. (1990). Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration. Am. J. Physiol. 258:G185-G190.

    PubMed  CAS  Google Scholar 

  25. Stralin, P., Karlsson, K., Johansson B.O., and Marklund, S.L. (1995). The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arteriosclerosis Thromb. Vasc. Biol. 15:2032–2036.

    CAS  Google Scholar 

  26. Fridovich, I. (1997). Superoxide anion radical (O2 ), superoxide dismutases, and related matters. J. Biol. Chem. 272: 18,515–18,517.

    Article  CAS  Google Scholar 

  27. Huang, T.T., Yasunami, M., Carlson, E.J., et al. (1997). Superoxide-mediated cytotoxicity in superoxide dismutase-deficient fetal fibroblasts. Arch. Biochem. Biophys. 344: 424–432.

    Article  PubMed  CAS  Google Scholar 

  28. McCord, J.M. and Fridovich, I. (1969). Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244:6049–6055.

    PubMed  CAS  Google Scholar 

  29. Epstein, C.J., Avraham, K.B., Lovett, M., et al. (1987). Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome. Proc. Natl. Acad. Sci. USA 84:8044–8048.

    Article  PubMed  CAS  Google Scholar 

  30. Horie, Y., Wolf, R. Flores, S.C., McCord, J.M., Epstein, C.J., and Granger, D.N. (1998). Transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to hepatic leukostasis and capillary no-reflow after gut ischemia/reperfusion. Circ. Res. 83:691–696.

    PubMed  CAS  Google Scholar 

  31. Uchimura, K., Nagasaka, A., Hayashi, R., et al. (1999). Changes in superoxide dismutase activities and concentrations and myeloperoxidase activities in leukocytes from patients with diabetes mellitus. J. Diabetes Complic. 13: 264–270.

    Article  CAS  Google Scholar 

  32. Grisham, M.B. (1992). Reactive Metabolites of Oxygen and Nitrogen in Biology and Medicine. R.G. Landes, Austin, TX.

    Google Scholar 

  33. Suzuki, M., Crisham, M.B., and Granger, D.N. (1991). Leukocyte-endothelial cell adhesive interactions: role of xanthine oxidase-derived oxidants. J. Leukocyte Biol. 50: 488–494.

    PubMed  CAS  Google Scholar 

  34. Kurose, I., Wolf, R., Grisham, M.B., Aw T.Y., Specian, R.D., and Granger, D.N. (1995). Microvascular responses to inhibitor of nitric oxide production. Role of active oxidants. Circ. Res. 76:30–39.

    PubMed  CAS  Google Scholar 

  35. Kokura, S., Wolf, R.E., Yoshikawa, T., Granger, D.N., and Aw, T.Y. (1999). Molecular mechanisms of neutrophil-endothelial cell adhesion induced by redox imbalance. Circ. Res. 84:516–524.

    PubMed  CAS  Google Scholar 

  36. Cho, S., Urata, Y., Iida, T., et al. (1998). Glutathione downregulates the phosphorylation of I kappa B: autoloop regulation of the NF-kappa B-mediated expression of NF-kappa B subunits by TNF-alpha in mouse vascular endothelial cells. Biochem. Biophys. Res. Commun. 253:104–108.

    Article  PubMed  CAS  Google Scholar 

  37. Rahman, I. and MacNee, W. (2000). Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radical Biol Med. 28:1405–1420.

    Article  CAS  Google Scholar 

  38. Cuboury, J., Woodman, R.C., Granger, D.N., Reinhardt, P., and Kubes, P. (1993). Nitric oxide prevents leukocyte adherence role of superoxide. Am. J. Physiol. 265:H862-H867.

    Google Scholar 

  39. Fox-Robichaud, A., Payne, D., Hasan, S.U., et al. (1998). Inhaled NO as a viable antiadhesive therapy/for ischemia/reperfusion injury of distal microvascular beds. J. Clin. Invest. 101:2497–2505.

    PubMed  CAS  Google Scholar 

  40. Kimura, M., Kurose, I., Russell, J., and Granger, D.N. (1997). Effect of fluvastatin on leukocyte-endothelial cell adhesion in hypercholesterolemic rats. Arteriosclerosis Thromb. Vasc. Biol. 17:1521–1526.

    CAS  Google Scholar 

  41. Kanner, J., Harel, S., and Granit, R. (1991). Nitric oxide as an antioxidant. Arch. Biochem. Biophys. 289:130–136.

    Article  PubMed  CAS  Google Scholar 

  42. Fujii, H., Ichimori, K., Hoshiai, K., and Nakazawa, H. (1997). Nitric oxide inactivates NADPH oxidase in pig neutrophils by inhibiting its assembling process. J. Biol. Chem. 272:32,773–32,778.

    Article  CAS  Google Scholar 

  43. Park, J.W. (1996). Attenuation of p47phox and p67phox membrane translocation as the inhibitory mechanism of S-nitrosothiol on the respiratory burst oxidase in human neutrophils. Biochem. Biophys. Res. Commun. 220:31–35.

    Article  PubMed  CAS  Google Scholar 

  44. Mugge, A., Elwell, J.H., Peterson, T.E., Hofmeyer, T.G., Heistad, D.D., and Harrison, D.G. (1991). Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ. Res. 69:1293–1300.

    PubMed  CAS  Google Scholar 

  45. White, C.R., Darley-Usmar, V., Berrington, W.R., et al. (1996). Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc. Natl. Acad. Sci. USA 93:8745–8749.

    Article  PubMed  CAS  Google Scholar 

  46. Lewis, M.S., Whatley, R.E., Cain, P., McIntyre, T.M., Prescott, S.M., and Zimmerman, G.A. (1988). Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. J. Clin. Invest. 82:2045–2055.

    PubMed  CAS  Google Scholar 

  47. Suzuki, M., Asako, H., Kubes, P., Jennings, S., Grisham, M.B., and Granger, D.N. (1991). Neutrophil-derived oxidants promote leukocyte adherence in postcapillary venules. Microvasc. Res. 42:125–138.

    Article  PubMed  CAS  Google Scholar 

  48. Patel, K.D., Zimmerman, G.A., Prescott, S.M., McEver, R.P., and McIntyre, T.M. (1991). Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J. Cell. Biol. 112:749–759.

    Article  PubMed  CAS  Google Scholar 

  49. Arai, T., Kelly, S.A. Brengman, M.L., et al. (1998). Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor alpha in endothelium. Biochem J. 331: 853–861.

    PubMed  CAS  Google Scholar 

  50. Grisham, M.B., Granger, D.N., and Lefer, D.J. (1998). Modulation of leukocyte-endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease. Free Radical Biol. Med. 25:404–433.

    Article  CAS  Google Scholar 

  51. Kubes, P., Grisham, M.B., Barrowman, J.A., Gaginella, T., and Granger, D.N. (1991). Leukocyte-induced vascular protein leakage in cat mesentery. Am. J. Physiol. 261: H1872-H1879.

    PubMed  CAS  Google Scholar 

  52. Yoshida, N., Granger, D.N., Anderson, D.C., Rothlein, R., Lane, C., and Kvietys, P.R. (1992). Anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Am. J. Physiol. 262:H1891-H1898.

    PubMed  CAS  Google Scholar 

  53. Kurose, I., Argenbright, L.W., Wolf, R., and Granger, D.N. (1996). Oxidative stress during platelet-activating factor-induced microvascular dysfunction. Microcirculation 3: 401–410.

    Article  PubMed  CAS  Google Scholar 

  54. Davidge, S.T. (2001). Prostaglandin H synthase and vascular function. Circ. Res. 89:650–660.

    PubMed  CAS  Google Scholar 

  55. DeForge, L.E., Preston, A.M., Takeuchi, E., Kenney, J., Boxer, L.A., and Remick, D.G. (1993). Regulation of interleukin 8 gene expression by oxidant stress. J. Biol. Chem. 268:25,568–25,576.

    CAS  Google Scholar 

  56. Kurose, I., Wolf, R., Grisham, M.B., and Granger, D.N. (1994). Modulation of ischemia/reperfusion-induced microvascular dysfunction by nitric oxide. Circ. Res. 74:376–382.

    PubMed  CAS  Google Scholar 

  57. Kurose, I., Wolf, R.E., Grisham, M.B., and Granger, D.N. (1998). Hypercholesterolemia enhances oxidant production in mesenteric venules exposed to Ischemia/Reperfusion. Arteriosclerosis Thromb. Vasc. Biol. 18:1583–1588.

    CAS  Google Scholar 

  58. Li, N., Hu, H., Lindqvist, M., Wikstrom-Jonsson, E., Goodall, A.H., and Hjemdahl, P. (2000). Platelet-leukocyte cross talk in whole blood. Arteriosclerosis Thromb. Vasc. Biol. 20:2702–2708.

    CAS  Google Scholar 

  59. Leo, R., Pratico, D., Iuliano L., et al. (1997). Platelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and then reoxygenated. Circulation 95:885–891.

    PubMed  CAS  Google Scholar 

  60. Granger, D.N. (1999). Ischemia-reperfusion: mechanisms of microvascular dysfunction and the influence of risk factors for cardiovascular disease. Microcirculation 6: 167–178.

    Article  PubMed  CAS  Google Scholar 

  61. Ichikawa, H., Flores, S., Kvietys, P.R., et al. (1997). Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Circ. Res. 81:922–931.

    PubMed  CAS  Google Scholar 

  62. Eppihimer, M.J., Russell, J., Anderson, D.C., Epstein, C.J., Laroux, S., and Granger, D.N. (1997). Modulation of P-selectin expression in the postischemic intestinal microvasculature. Am. J. Physiol. 273:G1326-G1332.

    PubMed  CAS  Google Scholar 

  63. Russell, J., Epstein, C.J., Grisham, M.B., Alexander, J.S., Yeh, K.Y., and Granger, D.N. (2000) Regulation of E-selectin expression in postischemic intestinal microvasculature. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G878-G885.

    PubMed  CAS  Google Scholar 

  64. Akgur, F.M., Brown, M.F., Zibari, G.B., et al. (2000). Role of superoxide in hemorrhagic shock-induced P-selectin expression. Am. J. Physiol. Heart Circ. Physiol. 279: H791-H797.

    PubMed  CAS  Google Scholar 

  65. Laufs, U., Gertz, K., Huang, P., et al. (2000). Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 31:2442–2449.

    PubMed  CAS  Google Scholar 

  66. Tailor, A. and Granger, D.N. (2001). Acute hypercholesterolemia and ischemia-reperfusion induced blood cell-endothelial cell adhesion in the murine mesenteric vascular bed. FASEB. J. 15:A35.

    Google Scholar 

  67. Cerwinka, W.H. and Granger, D.N. (2001). Influence of hypercholesterolemia and hypertension on ischemia-reperfusion induced P-selectin expression. Atherosclerosis 154:337–344.

    Article  PubMed  CAS  Google Scholar 

  68. Henninger, D.D., Gerritsen, M.E., and Granger, D.N. (1997). Low-density lipoprotein receptor knockout mice exhibit exaggerated microvascular responses to inflammatory stimuli. Circ. Res. 81:274–281.

    PubMed  CAS  Google Scholar 

  69. Guzik, T.J., West, N.E., Black, E., et al. (2000). Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ. Res. 86:E85-E90.

    PubMed  CAS  Google Scholar 

  70. Scalia, R., Appel, J.Z., III, and Lefer, A.M. (1998). Leukocyte-endothelium interaction during the early stages of hypercholesterolemia in the rabbit: role of P-selectin, ICAM-1, and VCAM-1. Arteriosclerosis Thromb. Vasc. Biol. 18: 1093–1100.

    CAS  Google Scholar 

  71. Gauthier, T.W., Scalia, R., Murohara, T., Guo, J.P., and Lefer, A.M. (1995). Nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia. Arteriosclerosis Thromb. Vasc. Biol. 15: 1652–1659.

    CAS  Google Scholar 

  72. Wassmann, S., Laufs, U., Muller, K., et al. (2002). Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arteriosclerosis Thromb Vasc. Biol. 22:300–305.

    Article  CAS  Google Scholar 

  73. Kurose, I., Argenbright, L.W., Anderson, D.C., et al. (1997). Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and hypercholesterolemic rats. Am. J. Physiol. 273:H854-H860.

    PubMed  CAS  Google Scholar 

  74. Panes, J., Kurose, I., Rodriguez-Vaca, D., et al. (1996). Diabetes exacerbates inflammatory responses to ischemia-reperfusion. Circulation 93:161–167.

    PubMed  CAS  Google Scholar 

  75. Salas, A., Panes, J., Rosenbloom, C.L., et al. (1999). Differential effects of a nitric oxide donor on reperfusion-induced microvascular dysfunction in diabetic and non-diabetic rats. Diabetologia 42:1350–1358.

    Article  PubMed  CAS  Google Scholar 

  76. Salas, A., Panes, J., Elizalde, J.I., Granger, D.N., and Pique, J.M. (1999). Reperfusion-induced oxidative stress in diabetes: cellular and enzymatic sources. J. Leukocyte Biol. 66:59–66.

    PubMed  CAS  Google Scholar 

  77. Kim, Y.K., Lee, M.S., Son, S.M., et al. (2002) Vascular NADH oxidase is involved in impaired endothelium-dependent vasodilation in OLETF rats, a model of type 2 diabetes. Diabetes 51:522–527.

    Article  PubMed  CAS  Google Scholar 

  78. Matata, B.M. and Galinanes, M. (2000). Cardiopulmonary by pass exacerbates oxidative stress but does not increase pro inflammatory cytokine release in patients with diabetes compared with patients without diabetes: regulatory effects of exogenous nitric oxide. J. Thorac. Cardiovasc. Surg. 120:1–11.

    Article  PubMed  CAS  Google Scholar 

  79. Kumar, C.A. and Das, U.N. (2000). Lipid peroxides, antioxidants and nitric oxide in patients with pre-eclampsia and essential hypertension. Med. Sci. Monit. 6:901–907.

    PubMed  CAS  Google Scholar 

  80. Schmid-Schonbein, G.W., Seiffge, D., DeLano, F.A., Shen, K., and Zweifach, B.W. (1991). Leukocyte counts and activation in spontaneously hypertensive and normotensive rats. Hypertension 17:323–330.

    PubMed  CAS  Google Scholar 

  81. Shen, K., DeLano, F.A., Zweifach, B.W., and Schmid-Schonbein, G.W. (1995). Circulating leukocyte counts, activation, and degranulation in Dahl hypertensive rats. Circ. Res. 76:276–283.

    PubMed  CAS  Google Scholar 

  82. Arndt, H., Smith, C.W., and Granger, D.N. (1993) Leukocyte-endothelial cell adhesion in spontaneously hypertensive and normotensive rats. Hypertension 21:667–673.

    PubMed  CAS  Google Scholar 

  83. Kurose, I., Wolf, R., Cerwinka, W., and Granger, D.N. (1999). Microvascular responses to ischemia/reperfusion in normotensive and hypertensive rats. Hypertension 34: 212–216.

    PubMed  CAS  Google Scholar 

  84. Tsujikawa, A., Kiryu, J., Yamashiro, K., et al. (2000). Interactions between blood cells and retinal endothelium in endotoxic sepsis. Hypertension 36:250–258.

    PubMed  CAS  Google Scholar 

  85. Alvarez, A. and Sanz, M.J. (2001). Reactive oxygen species mediate angiotensin II-induced leukocyte-endothelial cell interactions in vivo. J. Leukocyte Biol. 70:199–206.

    PubMed  CAS  Google Scholar 

  86. Mollnau, H., Wendt, M., Szocs, K., et al. (2002) Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ. Res. 90:E58-E65.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Neil Granger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cooper, D., Stokes, K.Y., Tailor, A. et al. Oxidative stress promotes blood cell-endothelial cell interactions in the microcirculation. Cardiovasc Toxicol 2, 165–180 (2002). https://doi.org/10.1007/s12012-002-0002-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-002-0002-7

Key Words

Navigation