High dietary salt intake decreases the endothelium-dependent dilation of skeletal muscle arterioles by inhibiting local nitric oxide (NO) activity without changing vascular smooth muscle responsiveness to NO. Under these conditions, microvascular walls show evidence of oxidative stress, and scavengers of reactive oxygen species (ROS) abolish this oxidative stress and restore normal arteriolar responses to acetylcholine (ACh). We tested the hypothesis that the salt-dependent appearance of microvascular ROS, and accompanying reduction in endothelium-dependent dilation, is due to a decrease in antioxidant enzyme expression or activity. We studied spinotrapezius muscle microvessels in rats fed normal (NS) (0.45%) or high (HS) (7%) salt diets for 4–5 weeks. Western analysis of arteriolar and venular protein showed no difference between groups in the content of superoxide dismutase (Cu/Zn SOD), catalase, or glutathione peroxidase. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) increased arteriolar and venular oxidant activity (assessed by tetranitroblue tetrazolium reduction) by the same amount in both groups, suggesting similar levels of catalase activity. 3AT did not affect arteriolar responses to ACh in either group. The Cu/Zn SOD inhibitor diethyldithiocarbamate increased arteriolar and venular oxidant activity to a lesser extent in HS rats, suggesting reduced Cu/Zn SOD activity in this group. Cu/Zn SOD inhibition decreased arteriolar responses to ACh only in NS rats. These findings suggest that endogenous Cu/Zn SOD preserves the endothelium-dependent control of arteriolar tone in NS rats, and that a reduction in Cu/Zn SOD activity contributes to the loss of arteriolar NO activity in HS rats.

Boegehold MA, KotchenTA: Effect of dietary salt on the skeletal muscle microvasculature in Dahl rats. Hypertension 1990;15:420–426.
Boegehold MA: Reduced influence of nitric oxide on arteriolar tone in hypertensive Dahl rats. Hypertension 1992;19:290–295.
Nurkiewicz TR, Boegehold MA: High dietary salt alters arteriolar myogenic responsiveness in normotensive and hypertensive rats. Am J Physiol 1998;275:H2095–H2104.
Swei A, Lacy F, DeLano FA, Schmid-Schönbein GW: Oxidative stress in the Dahl hypertensive rat. Hypertension 1997;30:1628–1633.
Boegehold MA: Effect of dietary salt on arteriolar nitric oxide in striated muscle of normotensive rats. Am J Physiol 1993;264:H1810–H1816.
Boegehold MA: Flow-dependent arteriolar dilation in normotensive rats fed low- or high-salt diets. Am J Physiol 1995;269:H1407–H1414.
Frisbee JC, Lombard JH: Chronic elevations in salt intake and reduced renal mass hypertension compromise mechanisms of arteriolar dilation. Microvasc Res 1998;56:218–227.
Liu Y, Fredricks KT, Roman RJ, Lombard JH: Response of resistance arteries to reduced PO2 and vasodilators during hypertension and elevated salt intake. Am J Physiol 1997;273:H869–H877.
Liu Y, Rusch NJ, Lombard JH: Loss of endothelium and receptor-mediated dilation in pial arterioles of rats fed a short-term high salt diet. Hypertension 1999;33:686–688.
Frisbee JC, Lombard JH: Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle. Microvasc Res 1999;57:273–283.
Lenda DM, Sauls BA, Boegehold MA: Reactive oxygen species may contribute to reduced endothelium-dependent dilation in rats fed high salt. Am J Physiol 2000;279:H7–H14.
Gryglewski RJ, Palmer RM, Moncada S: Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986;320:454–456.
Marshall JJ, Kontos HA: Acute microvascular injury mechanisms; in Bevan JA, Halpern W, Mulvany MJ (eds): The Resistance Vasculature. Totowa, Humana Press, 1991, pp 403–430.
Rubanyi GM, Vanhoutte PM: Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 1986;250:H822–H827.
Chen G, Wilson R, Boyd P, Mckillop JH, Leitch C, Walker JJ, Burdon RH: Normal superoxide dismutase (SOD) gene in pregnancy-induced hypertension: Is the decreased SOD activity a secondary phenomenon? Free Radic Res 1994;21:59–66.
Demaree SR, Lawler JM, Linehan J, Delp MD: Ageing alters aortic antioxidant enzyme activities in Fischer-344 rats. Acta Physiol Scand 1999;166:203–208.
Fukai T, Galis ZS, Meng XP, Parthasarathy S, Harrison DG: Vascular expression of extracellular superoxide dismutase in atherosclerosis. J Clin Invest 1998;101:2101–2111.
Fukai T, Siegfried MR, Ushio-Fukai M, Griendling KK, Harrison DG: Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res 1999;85:23–28.
Fukai T, Siegfried MR, Ushio-Fukai M, Cheng Y, Kojda G, Harrison DG: Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest 2000;105:1631–1639.
Inoue N, Ramasamy S, Fukai T, Nerem RM, Harrison DG: Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells. Circ Res 1996;79:32–37.
Pedro-Botet J, Covas MI, Martin S, Rubies-Prat J: Decreased endogenous antioxidant enzymatic status in essential hypertension. J Hum Hypertens 2000;14:343–345.
Woodman CR, Muller JM, Rush JW, Laughlin MH, Price EM: Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary arterioles. Am J Physiol 1999;276:H1058–H1063.
Harrison DG: Endothelial function and oxidant stress. Clin Cardiol 1997;20(suppl 2):II11–II17.
Crapo JD, Oury T, Rabouille C, Slot JW, Chang LY: Copper, zinc superoxide dismutase is primarily a cytosolic protein in human cells. Proc Natl Acad Sci USA 1992;89:10405–10409.
Gupte SA, Rupawalla T, Mohazzab H, Wolin MS: Regulation of NO-elicited pulmonary artery relaxation and guanylate cyclase activation by NADH oxidase and SOD. Am J Physiol 1999;276:H1535–H1542.
Beauchamp C, Fridovich I: Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels. Anal Biochem 1971;44:276–287.
Kontos HA, Wei EP, Ellis EF, Jenkins LW, Povlishock JT, Rowe GT, Hess ML: Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ Res 1985;57:142–151.
Friebel M, Klotz KF, Ley K, Gaehtgens P, Pries AR: Flow-dependent regulation of arteriolar diameter in rat skeletal muscle in situ: Role of endothelium-derived relaxing factor and prostanoids. J Physiol 1995;483:715–726.
Pries AR, Heide J, Ley K, Klotz K-F, Gaehtgens P: Effect of oxygen tension on regulation of arteriolar diameter in skeletal muscle in situ. Microvasc Res 1995;49:289–299.
Lash JM, Bohlen HG: Time- and order-dependent changes in functional and NO-mediated dilation during exercise training. J Appl Physiol 1997;82:460–468.
Grunfeld S, Hamilton CA, Mesaros S, McClain SW, Dominiczak AF, Bohr DF, Malinski T: Role of superoxide in the depressed nitric oxide production by the endothelium of genetically hypertensive rats. Hypertension 1995;26:854–857.
Ammar RF Jr, Gutterman DD, Brooks LA, Dellsperger KC: Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes. Cardiovasc Res 2000;47:595–601.
Mayhan WG, Sharpe GM: Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation: Effect of superoxide dismutase. J Appl Physiol 1999;86:1126–1134.
Mugge A, Elwell JH, Peterson TE, Harrison DG: Release of intact endothelium-derived relaxing factor depends on endothelial superoxide dismutase activity. Am J Physiol 1991;260:C219–C225.
Omar HA, Cherry PD, Mortelliti MP, Burke-Wolin T, Wolin MS: Inhibition of coronary artery superoxide dismutase attenuates endothelium-dependent and -independent nitrovasodilator relaxation. Circ Res 1991;69:601–608.
Cherry PD, Omar HA, Farrell KA, Stuart JS, Wolin MS: Superoxide anion inhibits cGMP-associated bovine pulmonary arterial relaxation. Am J Physiol 1990;259:H1056–H1062.
Kowaluk EA, Seth P, Fung HL: Metabolic activation of sodium nitroprusside to nitric oxide in vascular smooth muscle. J Pharmacol Exp Ther 1992;262:916–922.
Kaley G, Rodenburg JM, Messina EJ, Wolin MS: Endothelium-associated vasodilators in rat skeletal muscle microcirculation. Am J Physiol 1989;256:H720–H725.
Huang A, Sun D, Kaley G, Koller A: Superoxide released to high intra-arteriolar pressure reduces nitric oxide-mediated shear stress- and agonist-induced dilations. Circ Res 1998;83:960–965.
Linderman JR, Boegehold MA: Growth-related changes in the influence of nitric oxide on arteriolar tone. Am J Physiol 1999;277:H1570–H1578.
Wambi-Kiesse CO, Katusic ZS: Inhibition of copper/zinc superoxide dismutase impairs NO-mediated endothelium-dependent relaxations. Am J Physiol 1999;276:H1043–H1048.
Mattson DL, Higgins DJ: Influence of dietary sodium intake on renal medullary nitric oxide synthase. Hypertension 1996;27:688–692.
Ying W-Z, Sanders PW: Dietary salt increases endothelial nitric oxide synthase and TGF-β1 in rat aortic endothelium. Am J Physiol 1999;277:H1293–H1298.
Ni Z, Vaziri ND: Effect of salt loading on nitric oxide synthase expression in normotensive rats. Am J Hypertens 2001;14:155–163.
Ni Z, Oveisi F, Vaziri ND: Nitric oxide synthase isotype expression in salt-sensitive and salt-resistant Dahl rats. Hypertension 1999;34:552–557.
Griendling, KK, Sorescu D, Ushio-Fukai M: NAD(P)H oxidase: Role in cardiovascular biology and disease. Circ Res 2000;86:494–501.
Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 2000;87:840–844.
Swei A, Lacy F, Delano FA, Parks DA, Schmid-Schönbein GW: A mechanism of oxygen free radical production in the Dahl hypertensive rat. Microcirculation 1999;6:179–187.
Hansen-Smith FM, Morris LW, Greene AS, Lombard JH: Rapid microvessel rarefaction with elevated salt intake and reduced renal mass hypertension in rats. Circ Res 1996;79:324–330.
Greene AS, Yu ZY, Roman RJ, Cowley AW Jr: Role of blood volume expansion in Dahl rat model of hypertension. Am J Physiol 1990;258:H508–H514.
Roman RJ, Osborn JL: Renal function and sodium balance in conscious Dahl S and R rats. Am J Physiol 1987;252:R833–R841.
Bevan JA: Flow regulation of vascular tone. Its sensitivity to changes in sodium and calcium. Hypertension 1993;22:273–281.
Friedman S: Sodium ions and regulation of vascular tone. Adv Microcirc 1982;11:20–42.
McIntyre M, Bohr DF, Dominiczak AF: Endothelial function in hypertension. The role of superoxide anion. Hypertension 1999;34:539–545.
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