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Research Paper

Impaired Vasorelaxation in Inbred Mice Is Associated with Alterations in Both Nitric Oxide and Super Oxide Pathways

Chen C. · Korshunov V.A. · Massett M.P. · Yan C. · Berk B.C.

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Cardiovascular Research Institute, Department of Medicine, University of Rochester, Rochester, N.Y., USA

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J Vasc Res 2007;44:504–512

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: March 12, 2007
Accepted: May 25, 2007
Published online: July 30, 2007
Issue release date: October 2007

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR

Abstract

Recently, we showed that genetic factors determine flow-dependent vascular remodeling. Among five inbred mouse strains, the SJL strain developed the largest intima in response to low flow. Because SJL mice have a spontaneous mutation in superoxide dismutase 2 (SOD-2) we tested the hypothesis that strain-specific variations in vascular function are due to alterations in redox and nitric oxide (NO) pathways. Vasorelaxation to acetylcholine was significantly impaired in aortic rings from SJL compared to C3H or FVB mice (up to 40%). Relaxation to the endothelium-independent vasodilator sodium nitroprusside (SNP) in SJL mice was also significantly impaired at low concentrations, with decreases in sensitivity and maximal relaxation to SNP compared to C3H and FVB mice. Western blot analyses showed significantly decreased expression (∼40%) of eNOS, PKG and SOD-2 proteins in SJL vasculature compared to C3H. Intact aortas from SJL showed significantly increased nitrotyrosine and decreased SOD-2 expression compared to C3H by immunohistochemistry. Basal levels of superoxide in aortas from SJL were not significantly different than C3H as measured by dihydroethidine. In summary, relatively small alterations in redox (SOD-2) and NO pathways (eNOS and PKG) may contribute to significantly impaired vasorelaxation in SJL mice.

© 2007 S. Karger AG, Basel


References

  1. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr: Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999;340:14–22.
  2. Fox CS, Polak JF, Chazaro I, et al: Genetic and environmental contributions to atherosclerosis phenotypes in men and women: heritability of carotid intima-media thickness in the Framingham heart study. Stroke 2003;34:397–401.
  3. Stone PH, Coskun AU, Kinlay S, et al: Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans. In vivo 6-month follow-up study. Circulation 2003;108:438–444.
  4. Wentzel JJ, Janssen E, Vos J, et al: Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling. Circulation 2003;108:17–23.
  5. Korshunov VA, Berk BC: Flow-induced vascular remodeling in the mouse: a model for carotid intima-media thickening. Arterioscler Thromb Vasc Biol 2003;23:2185–2191.
  6. Korshunov VA, Berk BC: Strain-dependent vascular remodeling: the ‘Glagov phenomenon’ is genetically determined. Circulation 2004;110:220–226.
  7. Korshunov VA, Nikonenko TA, Tkachuk VA, Brooks A, Berk BC: Interleukin-18 and macrophage migration inhibitory factor are associated with increased carotid intima-media thickening. Arterioscler Thromb Vasc Biol 2006;26:295–300.
  8. Kohler TR, Kirkman TR, Kraiss LW, Zierler BK, Clowes AW: Increased blood flow inhibits neointimal hyperplasia in endothelialized vascular grafts. Circ Res 1991;69:1557–1565.
  9. Langille BL, O’Donnell F: Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 1986;231:405–407.
  10. Tronc F, Wassef M, Esposito B, Henrion D, Glagov S, Tedgui A: Role of NO in flow-induced remodeling of the rabbit common carotid artery. Arterioscler Thromb Vasc Biol 1996;16:1256–1262.
  11. Huang PL, Huang Z, Mashimo H, et al: Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995;377:239–242.
  12. Rudic RD, Shesely EG, Maeda N, Smithies O, Segal SS, Sessa WC: Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J Clin Invest 1998;101:731–736.
  13. Channon KM, Qian H, George SE: Nitric oxide synthase in atherosclerosis and vascular injury: insights from experimental gene therapy. Arterioscler Thromb Vasc Biol 2000;20:1873–1881.
  14. Forsberg L, de Faire U, Morgenstern R: Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 2001;389:84–93.
  15. Fukai T, Folz RJ, Landmesser U, Harrison DG: Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc Res 2002;55:239–249.
  16. Cooke CL, Davidge ST: Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice. Cardiovasc Res 2003;60:635–642.
  17. Mollnau H, Wendt M, Szocs K, et al: Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 2002;90:E58–E65.
  18. Guo Z, Higuchi K, Mori M: Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Free Radic Biol Med 2003;35:1645–1652.
  19. Ohashi M, Runge MS, Faraci FM, Heistad DD: MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2006;26:2331–2336.
  20. Ryan MJ, Didion SP, Davis DR, Faraci FM, Sigmund CD: Endothelial dysfunction and blood pressure variability in selected inbred mouse strains. Arterioscler Thromb Vasc Biol 2002;22:42–48.
  21. Kojda G, Laursen JB, Ramasamy S, et al: Protein expression, vascular reactivity and soluble guanylate cyclase activity in mice lacking the endothelial cell nitric oxide synthase: contributions of NOS isoforms to blood pressure and heart rate control. Cardiovasc Res 1999;42:206–213.
  22. Linder AE, Weber DS, Whitesall SE, D’Alecy LG, Webb RC: Altered vascular reactivity in mice made hypertensive by nitric oxide synthase inhibition. J Cardiovasc Pharmacol 2005;46:438–444.
  23. Kim D, Rybalkin SD, Pi X, et al: Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation 2001;104:2338–2343.
  24. Freiman PC, Mitchell GG, Heistad DD, Armstrong ML, Harrison DG: Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ Res 1986;58:783–789.
  25. Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD: Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5′-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 1987;79:170–174.
  26. Mueller CF, Laude K, McNally JS, Harrison DG: Redox mechanisms in blood vessels. Arterioscler Thromb Vasc Biol 2005;25:274–278.
  27. Rodriguez-Iturbe B, Sepassi L, Quiroz Y, Ni Z, Wallace DC, Vaziri ND: Association of mitochondrial SOD deficiency with salt-sensitive hypertension and accelerated renal senescence. J Appl Physiol 2007;102:255–260.
  28. Li Y, Huang TT, Carlson EJ, et al: Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 1995;11:376–381.
  29. Kawashima S, Yokoyama M: Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 2004;24:998–1005.
  30. Knowles JW, Reddick RL, Jennette JC, Shesely EG, Smithies O, Maeda N: Enhanced atherosclerosis and kidney dysfunction in eNOS(–/–)Apoe(–/–) mice are ameliorated by enalapril treatment. J Clin Invest 2000;105:451–458.
  31. Lincoln TM, Dey N, Sellak H: Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 2001;91:1421–1430.
  32. Pfeifer A, Klatt P, Massberg S, et al: Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 1998;17:3045–3051.
  33. Murakami K, Kondo T, Kawase M, et al: Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J Neurosci 1998;18:205–213.
  34. Kim GW, Kondo T, Noshita N, Chan PH: Manganese superoxide dismutase deficiency exacerbates cerebral infarction after focal cerebral ischemia/reperfusion in mice: implications for the production and role of superoxide radicals. Stroke 2002;33:809–815.
  35. Asimakis GK, Lick S, Patterson C: Postischemic recovery of contractile function is impaired in SOD2(+/–) but not SOD1(+/–) mouse hearts. Circulation 2002;105:981–986.
  36. Fujii M, Hara H, Meng W, Vonsattel JP, Huang Z, Moskowitz MA: Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke 1997;28:1805–1810; discussion 1811.
  37. Lambertsen KL, Gregersen R, Finsen B: Microglial-macrophage synthesis of tumor necrosis factor after focal cerebral ischemia in mice is strain dependent. J Cereb Blood Flow Metab 2002;22:785–797.
  38. Korytova LI, Gubareva AV: Effect of ascorbic acid on the development of a spontaneous lymphoproliferative process in SJL/J-strain mice (in Russian). Eksp Onkol 1986;8:63–65.

Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: March 12, 2007
Accepted: May 25, 2007
Published online: July 30, 2007
Issue release date: October 2007

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR


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