Oxidant production and regulation is becoming increasingly important in the study of vascular signaling mechanisms, and recent reviews have characterized some of the possible roles for known downstream products of superoxide formation. In this review, we will examine current research in the field, with a special emphasis on the role of the superoxide molecule itself and its place amongst the slightly better understood roles of peroxide and peroxynitrite. The regulatory roles of oxidant species are wide-ranging, and their involvement in processes ranging from intracellular and receptor signaling mechanisms that regulate endothelial mediator release and vascular contractile function to processes that control cellular growth and apoptosis has been implied. Cellular sources of superoxide production and metabolism and the chemical interaction of oxidant species with specific components of cellular signaling mechanisms are considered important factors which determine physiological responses that control vascular function.

Keywords:
Superoxide, Oxidant signaling, Nitric oxide, Endothelium, Vascular function, Peroxynitrite, Peroxide, Redox signaling
1.
Griendling KK, Harrison DG: Dual role of reactive oxygen species in vascular growth. Circ Res 1999;85:562–563.
2.
Wolin MS: Reactive oxygen species and vascular signal transduction mechanisms. Microcirculation 1996;3:1–17.
3.
Wolin MS: Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 2000;20:1430–1442.
4.
Fridovich I: Superoxide radical: An endogenous toxicant. Annu Rev Pharmacol Toxicol 1983;23:239–257.
5.
Pryor WA, Squadrito GL: The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide. Am J Physiol 1995;268:L699–L722.
6.
Griendling KK, Sorescu D, Ushio-Fukai M: NAD(P)H oxidase: Role in cardiovascular biology and disease. Circ Res 2000;86:494–501.
7.
Lassegue B, Sorescu D, Szocs K, Yin Q, Akers M, Zhang Y, Grant SL, Lambeth JD, Griendling KK: Novel gp91(phox) homologues in vascular smooth muscle cells: Nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 2001;88:888–894.
8.
Boveris A: Mitochondrial production of superoxide radical and hydrogen peroxide. Adv Exp Med Biol 1977;78:67–82.
9.
Archer SL, Weir EK, Reeve HL, Michelakis E: Molecular identification of O2 sensors and O2-sensitive potassium channels in the pulmonary circulation. Adv Exp Med Biol 2000;475:219–240.
10.
Waypa GB, Chandel NS, Schumacker PT: Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res 2001;88:1259–1266.
11.
Jones SA, O’Donnell VB, Wood JD, Broughton JP, Hughes EJ, Jones OT: Expression of phagocyte NADPH oxidase components in human endothelial cells. Am J Physiol 1996;271:H1626–H1634.
12.
Mohazzab-H KM, Kaminski PM, Wolin MS: NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium. Am J Physiol 1994;266:H2568–H2572.
13.
Mohazzab-H KM, Wolin MS: Properties of a superoxide anion-generating microsomal NADH oxidoreductase, a potential pulmonary artery PO2 sensor. Am J Physiol 1994;267:L823–L831.
14.
Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW: Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994;74:1141–1148.
15.
Pagano PJ, Chanock SJ, Siwik DA, Colucci WS, Clark JK: Angiotensin II induces p67phox mRNA expression and NADPH oxidase superoxide generation in rabbit aortic adventitial fibroblasts. Hypertension 1998;32:331–337.
16.
Babior BM: NADPH oxidase: An update. Blood 1999;93:1464–1476.
17.
Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, Nyengaard JR, van den Enden M, Kilo C, Tilton RG: Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 1993;42:801–813.
18.
Gupte SA, Rupawalla T, Mohazzab-H KM, 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.
19.
Wolin MS, Burke-Wolin TM, Mohazzab-H KM: Roles for NAD(P)H oxidases and reactive oxygen species in vascular oxygen sensing mechanisms. Respir Physiol 1999;115:229–238.
20.
Kummer W, Acker H: Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase in type I cells of carotid body. J Appl Physiol 1995;78:1904–1909.
21.
Ushio-Fukai M, Alexander RW, Akers M, Yin Q, Fujio Y, Walsh K, Griendling KK: Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells. J Biol Chem 1999;274:22699–22704.
22.
Harrison DG: Endothelial function and oxidant stress. Clin Cardiol 1997;20(11 suppl 2):II-11–II-17.
23.
Griendling KK, Ushio-Fukai M, Lassegue B, Alexander RW: Angiotensin II signaling in vascular smooth muscle. New concepts. Hypertension 1997;29:366–373.
24.
Stoclet JC, Muller B, Andriantsitohaina R, Kleschyov A: Overproduction of nitric oxide in pathophysiology of blood vessels. Biochemistry (Mosc) 1998;63:826–832.
25.
Bouloumie A, Bauersachs J, Linz W, Scholkens BA, Wiemer G, Fleming I, Busse R: Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production. Hypertension 1997;30:934–941.
26.
Xia Y, Tsai AL, Berka V, Zweier JL: Superoxide generation from endothelial nitric-oxide synthase. A Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process. J Biol Chem 1998;273:25804–25808.
27.
Meininger CJ, Marinos RS, Hatakeyama K, Martinez-Zaguilan R, Rojas JD, Kelly KA, Wu G: Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. Biochem J 2000;349:353–356.
28.
Jiang J, Valen G, Tokuno S, Thoren P, Pernow J: Endothelial dysfunction in atherosclerotic mice: Improved relaxation by combined supplementation with L-arginine-tetrahydrobiopterin and enhanced vasoconstriction by endothelin. Br J Pharmacol 2000;131:1255–1261.
29.
Heitzer T, Brockhoff C, Mayer B, Warnholtz A, Mollnau H, Henne S, Meinertz T, Munzel T: Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers: Evidence for a dysfunctional nitric oxide synthase. Circ Res 2000;86:E36–E41.
30.
Bai J, Cederbaum AI: Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against cytochrome P450 2E1-dependent toxicity in HepG2 cells. J Biol Chem 2001;276:4315–4321.
31.
Fleming I, Michaelis UR, Bredenkotter D, Fisslthaler B, Dehghani F, Brandes RP, Busse R: Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ Res 2001;88:44–51.
32.
Orellana BM, Guajardo V, Araya J, Thieleman L, Rodrigo R: Oxidative stress, microsomal and peroxisomal fatty acid oxidation in the liver of rats treated with acetone. Comp Biochem Physiol C Toxicol Pharmacol 2001;128:503–509.
33.
Kukreja RC, Kontos HA, Hess ML, Ellis EF: PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH. Circ Res 1986;59:612–619.
34.
Holland JA, Pritchard KA, Pappolla MA, Wolin MS, Rogers NJ, Stemerman MB: Bradykinin induces superoxide anion release from human endothelial cells. J Cell Physiol 1990;143:21–25.
35.
Marshall JJ, Kontos HA: Endothelium-derived relaxing factors. A perspective from in vivo data. Hypertension 1990;16:371–386.
36.
Granger DN: Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol 1988;255:H1269–H1275.
37.
Beetsch JW, Park TS, Dugan LL, Shah AR, Gidday JM: Xanthine oxidase-derived superoxide causes reoxygenation injury of ischemic cerebral endothelial cells. Brain Res 1998;786:89–95.
38.
Weir EK, Archer SL: The mechanism of acute hypoxic pulmonary vasoconstriction: The tale of two channels. FASEB J 1995;9:183–189.
39.
von Harsdorf R, Li PF, Dietz R: Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation 1999;99:2934–2941.
40.
Cadenas E, Davies KJ: Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000;29:222–230.
41.
Liu L, Trimarchi JR, Keefe DL: Involvement of mitochondria in oxidative stress-induced cell death in mouse zygotes. Biol Reprod 2000;62:1745–1753.
42.
Panaretakis T, Shabalina IG, Grander D, Shoshan MC, DePierre JW: Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma HepG2 cells by the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid. Toxicol Appl Pharmacol 2001;173:56–64.
43.
Fridovich I: Superoxide dismutases: Regularities and irregularities. Harvey Lect 1983–84;79:51–75.
44.
Gow AJ, Ischiropoulos H: Nitric oxide chemistry and cellular signaling. J Cell Physiol 2001;187:277–282.
45.
Stralin P, Karlsson K, Johansson BO, Marklund SL: The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arterioscler Thromb Vasc Biol 1995;15:2032–2036.
46.
Rowland LP, Shneider NA: Amyotrophic lateral sclerosis. N Engl J Med 2001;344:1688–1700.
47.
Sampson JB, Beckman JS: Hydrogen peroxide damages the zinc-binding site of zinc-deficient Cu,Zn superoxide dismutase. Arch Biochem Biophys 2001;392:8–13.
48.
Wolin MS, Davidson CA, Kaminski PM, Fayngersh RP, Mohazzab-H KM: Oxidant-nitric oxide signalling mechanisms in vascular tissue. Biochemistry (Mosc) 1998;63:810–816.
49.
Goodwin DC, Rowlinson SW, Marnett LJ: Substitution of tyrosine for the proximal histidine ligand to the heme of prostaglandin endoperoxide synthase 2: Implications for the mechanism of cyclooxygenase activation and catalysis. Biochemistry 2000;39:5422–5432.
50.
Wolin MS, Rodenburg JM, Messina EJ, Kaley G: Similarities in the pharmacological modulation of reactive hyperemia and vasodilation to hydrogen peroxide in rat skeletal muscle arterioles: Effects of probes for endothelium-derived mediators. J Pharmacol Exp Ther 1990;253:508–512.
51.
Gurtner GH, Burke-Wolin T: Interactions of oxidant stress and vascular reactivity. Am J Physiol 1991;260:L207–L211.
52.
Landino LM, Crews BC, Timmons MD, Morrow JD, Marnett LJ: Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc Natl Acad Sci USA 1996;93:15069–15074.
53.
Upmacis RK, Deeb RS, Hajjar DP: Regulation of prostaglandin H2 synthase activity by nitrogen oxides. Biochemistry 1999;38:12505–12513.
54.
Camacho M, Lopez-Belmonte J, Vila L: Rate of vasoconstrictor prostanoids released by endothelial cells depends on cyclooxygenase-2 expression and prostaglandin I synthase activity. Circ Res 1998;83:353–365.
55.
Burke TM, Wolin MS: Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation. Am J Physiol 1987;252:H721–H732.
56.
Cosentino F, Katusic ZS: Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries. Circulation 1995;91:139–144.
57.
Ullrich V, Brune B, Hecker G, Schmidt KU, Mulsch A, Busse R: Physiological targets of superoxide anion and hydrogen peroxide in reperfusion injury. Free Radic Res Commun 1989;7:265–274.
58.
Kim BY, Han MJ, Chung AS: Effects of reactive oxygen species on proliferation of Chinese hamster lung fibroblast (V79) cells. Free Radic Biol Med 2001;30:686–698.
59.
Oeckler RA, Wolin MS: Stretch enhances contractile responses in bovine coronary and pulmonary arteries: Potential role of NADH oxidase-derived peroxide and activation of the ERK MAP kinase cascade. Circulation 2001;104:II-605 (abstract).
60.
Garrington TP, Johnson GL: Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol 1999;11:211–218.
61.
Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan KL: Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Mol Cell Biol 1999;19:5523–5534.
62.
Helmbrecht K, Zeise E, Rensing L: Chaperones in cell cycle regulation and mitogenic signal transduction: A review. Cell Prolif 2000;33:341–365.
63.
Nowicki PT, Flavahan S, Hassanain H, Mitra S, Holland S, Goldschmidt-Clermont PJ, Flavahan NA: Redox signaling of the arteriolar myogenic response. Circ Res 2001;89:114–116.
64.
Lee SL, Simon AR, Wang WW, Fanburg BL: H2O2 signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2001;281:L646–L652.
65.
Amin JK, Xiao L, Pimental DR, Pagano PJ, Singh K, Sawyer DB, Colucci WS: Reactive oxygen species mediate α-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol 2001;33:131–139.
66.
Yang JQ, Li S, Huang Y, Zhang HJ, Domann FE, Buettner GR, Oberley LW: V-Ha-Ras overexpression induces superoxide production and alters levels of primary antioxidant enzymes. Antioxid Redox Signal 2001;3:697–709.
67.
Korchak HM, Kilpatrick LE: TNF-α elicits association of PI 3-kinase with the p60TNFR and activation of PI 3-kinase in adherent neutrophils. Biochem Biophys Res Commun 2001;281:651–656.
68.
Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 2000;87:840–844.
69.
Wolin MS, Hintze TH, Shen W, Mohazzab-H KM, Xie YW: Involvement of reactive oxygen and nitrogen species in signalling mechanisms that control tissue respiration in muscle. Biochem Soc Trans 1997;25:934–939.
70.
Davidson CA, Kaminski PM, Wolin MS: NO elicits prolonged relaxation of bovine pulmonary arteries via endogenous peroxynitrite generation. Am J Physiol 1997;273:L437–L444.
71.
Gardner PR: Superoxide-driven aconitase FE-S center cycling. Biosci Rep 1997;17:33–42.
72.
Gardner PR, Raineri I, Epstein LB, White CW: Superoxide radical and iron modulate aconitase activity in mammalian cells. J Biol Chem 1995;270:13399–13405.
73.
Zou M, Yesilkaya A, Ullrich V: Peroxynitrite inactivates prostacyclin synthase by heme-thiolate-catalyzed tyrosine nitration. Drug Metab Rev 1999;31:343–349.
74.
Zou M, Jendral M, Ullrich V: Prostaglandin endoperoxide-dependent vasospasm in bovine coronary arteries after nitration of prostacyclin synthase. Br J Pharmacol 1999;126:1283–1292.
75.
Takakura K, Beckman JS, MacMillan-Crow LA, Crow JP: Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite. Arch Biochem Biophys 1999;369:197–207.
76.
Barrett WC, DeGnore JP, Keng YF, Zhang ZY, Yim MB, Chock PB: Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B. J Biol Chem 1999;274:34543–34546.
77.
Callsen D, Sandau KB, Brune B: Nitric oxide and superoxide inhibit platelet-derived growth factor receptor phosphotyrosine phosphatases. Free Radic Biol Med 1999;26:1544–1553.
78.
Padmaja S, Squadrito GL, Pryor WA: Inactivation of glutathione peroxidase by peroxynitrite. Arch Biochem Biophys 1998;349:1–6.
79.
Quijano C, Hernandez-Saavedra D, Castro L, McCord JM, Freeman BA, Radi R: Reaction of peroxynitrite with Mn-superoxide dismutase. Role of the metal center in decomposition kinetics and nitration. J Biol Chem 2001;276:11631–11638.
80.
Crow JP, Beckman JS, McCord JM: Sensitivity of the essential zinc-thiolate moiety of yeast alcohol dehydrogenase to hypochlorite and peroxynitrite. Biochemistry 1995;34:3544–3552.
81.
Riobo NA, Clementi E, Melani M, Boveris A, Cadenas E, Moncada S, Poderoso JJ: Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation. Biochem J 2001;359:139–145.
82.
Kirsch M, de Groot H: Reaction of peroxynitrite with reduced nicotinamide nucleotides, the formation of hydrogen peroxide. J Biol Chem 1999;274:24664–24670.
83.
Boota A, Zar H, Kim YM, Johnson B, Pitt B, Davies P: IL-1β stimulates superoxide and delayed peroxynitrite production by pulmonary vascular smooth muscle cells. Am J Physiol 1996;271:L932–L938.
84.
Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS: Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 1992;298:431–437.
85.
Mukhopadhyay CK, Fox PL: Ceruloplasmin copper induces oxidant damage by a redox process utilizing cell-derived superoxide as reductant. Biochemistry 1998;37:14222–14229.
86.
Podrez EA, Abu-Soud HM, Hazen SL: Myeloperoxidase-generated oxidants and atherosclerosis. Free Radic Biol Med 2000;28:1717–1725.
87.
Cathcart MK, McNally AK, Chisolm GM: Lipoxygenase-mediated transformation of human low density lipoprotein to an oxidized and cytotoxic complex. J Lipid Res 1991;32:63–70.
88.
Hirata H, Asanuma M, Cadet JL: Superoxide radicals are mediators of the effects of methamphetamine on Zif268 (Egr-1, NGFI-A) in the brain: Evidence from using CuZn superoxide dismutase transgenic mice. Brain Res Mol Brain Res 1998;58:209–216.
89.
Galle J, Heinloth A, Wanner C, Heermeier K: Dual effect of oxidized LDL on cell cycle in human endothelial cells through oxidative stress. Kidney Int Suppl 2001;78:S120–S123.
90.
Knapp LT, Klann E: Superoxide-induced stimulation of protein kinase C via thiol modification and modulation of zinc content. J Biol Chem 2000;275:24136–24145.
91.
Li JM, Mullen AM, Shah AM: Phenotypic properties and characteristics of superoxide production by mouse coronary microvascular endothelial cells. J Mol Cell Cardiol 2001;33:1119–1131.
92.
Griendling KK, Sorescu D, Lassegue B, Ushio-Fukai M: Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 2000;20:2175–2183.
93.
Repine JE, Cheronis JC, Rodell TC, Linas SL, Patt A: Pulmonary oxygen toxicity and ischemia-reperfusion injury. A mechanism in common involving xanthine oxidase and neutrophils. Am Rev Respir Dis 1987;136:483–485.
94.
Harder DR, Campbell WB, Roman RJ: Role of cytochrome P-450 enzymes and metabolites of arachidonic acid in the control of vascular tone. J Vasc Res 1995;32:79–92.
95.
Lagrange P, Romero IA, Minn A, Revest PA: Transendothelial permeability changes induced by free radicals in an in vitro model of the blood-brain barrier. Free Radic Biol Med 1999;27:667–672.
96.
Wood JG, Johnson JS, Mattioli LF, Gonzalez NC: Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats. J Appl Physiol 2000;89:1561–1568.
97.
Kerkar S, Speyer C, Tyburski J, Steffes C: Reactive oxygen metabolites induce a biphasic contractile response in microvascular lung pericytes. J Trauma 2001;51:440–445.
98.
Aoki T, Suzuki Y, Nishio K, Suzuki K, Miyata A, Oyamada Y, Mori M, Fujita H, Yamaguchi K: Effect of antioxidants on hyperoxia-induced ICAM-1 expression in human endothelial cells. Adv Exp Med Biol 1997;411:503–511.
99.
Chiu JJ, Wung BS, Shyy JY, Hsieh HJ, Wang DL: Reactive oxygen species are involved in shear stress-induced intercellular adhesion molecule-1 expression in endothelial cells. Arterioscler Thromb Vasc Biol 1997;17:3570–3577.
100.
Tummala PE, Chen XL, Medford RM: NF-κB independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production. J Mol Cell Cardiol 2000;32:1499–1508.
101.
Lounsbury KM, Hu Q, Ziegelstein RC: Calcium signaling and oxidant stress in the vasculature. Free Radic Biol Med 2000;28:1362–1369.
102.
Elliott SJ, Koliwad SK: Redox control of ion channel activity in vascular endothelial cells by glutathione. Microcirculation 1997;4:341–347.
103.
Sorescu D, Somers MJ, Lassegue B, Grant S, Harrison DG, Griendling KK: Electron spin resonance characterization of the NAD(P)H oxidase in vascular smooth muscle cells. Free Radic Biol Med 2001;30:603–612.
104.
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.
105.
Omar HA, Figueroa R, Omar RA, Tejani N, Wolin MS: Hydrogen peroxide and reoxygenation cause prostaglandin-mediated contraction of human placental arteries and veins. Am J Obstet Gynecol 1992;167:201–207.
106.
Figueroa R, Martinez E, Fayngersh RP, Tejani N, Mohazzab-H KM, Wolin MS: Alterations in relaxation to lactate and H2O2 in human placental vessels from gestational diabetic pregnancies. Am J Physiol Heart Circ Physiol 2000;278:H706–H713.
107.
Jin N, Rhoades RA: Activation of tyrosine kinases in H2O2-induced contraction in pulmonary artery. Am J Physiol 1997;272:H2686–H2692.
108.
Di Wang H, Hope S, Du Y, Quinn MT, Cayatte A, Pagano PJ, Cohen RA: Paracrine role of adventitial superoxide anion in mediating spontaneous tone of the isolated rat aorta in angiotensin II-induced hypertension. Hypertension 1999;33:1225–1232.
109.
Iesaki T, Wolin MS: Thiol oxidation activates a novel redox-regulated coronary vasodilator mechanism involving inhibition of Ca2+ influx. Arterioscler Thromb Vasc Biol 2000;20:2359–2365.
110.
Fearon IM, Palmer AC, Balmforth AJ, Ball SG, Varadi G, Peers C: Modulation of recombinant human cardiac L-type Ca2+ channel α1C subunits by redox agents and hypoxia. J Physiol 1999;514:629–637.
111.
Zhong J, Hume JR, Keef KD: Beta-adrenergic receptor stimulation of L-type Ca2+ channels in rabbit portal vein myocytes involves both α and βγ G protein subunits. J Physiol 2001;531:105–115.
112.
Liu Y, Terata K, Rusch NJ, Gutterman DD: High glucose impairs voltage-gated K+ channel current in rat small coronary arteries. Circ Res 2001;89:146–152.
113.
Tokube K, Kiyosue T, Arita M: Effects of hydroxyl radicals on KATP channels in guinea-pig ventricular myocytes. Pflügers Arch 1998;437:155–157.
114.
Clement MV, Pervaiz S: Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: An hypothesis. Free Radic Res 1999;30:247–252.
115.
Irani K, Goldschmidt-Clermont PJ: Ras, superoxide and signal transduction. Biochem Pharmacol 1998;55:1339–1346.
116.
Kamata H, Hirata H: Redox regulation of cellular signalling. Cell Signal 1999;11:1–14.
117.
Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K, Minowa O, Miyazono K, Noda T, Ichijo H: ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2001;2:222–228.
118.
Griendling KK, Ushio-Fukai M: Redox control of vascular smooth muscle proliferation. J Lab Clin Med 1998;132:9–15.
119.
Skulachev VP: Why are mitochondria involved in apoptosis? Permeability transition pores and apoptosis as selective mechanisms to eliminate superoxide-producing mitochondria and cell. FEBS Lett 1996;397:7–10.
120.
Vercesi AE, Kowaltowski AJ, Grijalba MT, Meinicke AR, Castilho RF: The role of reactive oxygen species in mitochondrial permeability transition. Biosci Rep 1997;17:43–52.
121.
Halestrap AP: The mitochondrial permeability transition: Its molecular mechanism and role in reperfusion injury. Biochem Soc Symp 1999;66:181–203.
122.
Brown GC: Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1999;1411:351–369.
123.
Kroemer G, Dallaporta B, Resche-Rigon M: The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 1998;60:619–642.
124.
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999;397:441–446.
125.
Skulachev VP: Mitochondria in the programmed death phenomena; a principle of biology: ‘It is better to die than to be wrong’. IUBMB Life 2000;49:365–373.
126.
Cho A, Courtman DW, Langille BL: Apoptosis (programmed cell death) in arteries of the neonatal lamb. Circ Res 1995;76:168–175.
127.
Alexander RW: Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: A new perspective. Hypertension 1995;25:155–161.
128.
Sorescu D, Szocs K, Griendling KK: NAD(P)H oxidases and their relevance to atherosclerosis. Trends Cardiovasc Med 2001;11:124–131.
129.
Rueckschloss U, Galle J, Holtz J, Zerkowski HR, Morawietz H: Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: Antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 2001;104:1767–1772.
130.
Azumi H, Inoue N, Takeshita S, Rikitake Y, Kawashima S, Hayashi Y, Itoh H, Yokoyama M: Expression of NADH/NADPH oxidase p22phox in human coronary arteries. Circulation 1999;100:1494–1498.
131.
Haddad JJ, Safieh-Garabedian B, Saade NE, Land SC: Thiol regulation of pro-inflammatory cytokines reveals a novel immunopharmacological potential of glutathione in the alveolar epithelium. J Pharmacol Exp Ther 2001;296:996–1005.
132.
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.
133.
Wagner AH, Kohler T, Ruckschloss U, Just I, Hecker M: Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 2000;20:61–69.
134.
Wagner AH, Schroeter MR, Hecker M: 17β-Estradiol inhibition of NADPH oxidase expression in human endothelial cells. FASEB J 2001;15:2121–2130.
135.
Kristensen SD, Lassen JF, Ravn HB: Pathophysiology of coronary thrombosis. Semin Interv Cardiol 2000;5:109–115.
136.
Johnson JL, Jackson CL: Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse. Atherosclerosis 2001;154:399–406.
137.
Kahler J, Ewert A, Weckmuller J, Stobbe S, Mittmann C, Koster R, Paul M, Meinertz T, Munzel T: Oxidative stress increases endothelin-1 synthesis in human coronary artery smooth muscle cells. J Cardiovasc Pharmacol 2001;38:49–57.
138.
Beauchamp P, Richard V, Tamion F, Lallemand F, Lebreton JP, Vaudry H, Daveau M, Thuillez C: Protective effects of preconditioning in cultured rat endothelial cells: Effects on neutrophil adhesion and expression of ICAM-1 after anoxia and reoxygenation. Circulation 1999;100:541–546.
139.
Beresewicz A, Czarnowska E, Maczewski M: Ischemic preconditioning and superoxide dismutase protect against endothelial dysfunction and endothelium glycocalyx disruption in the postischemic guinea-pig hearts. Mol Cell Biochem 1998:186:87–97.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.