title: Comparison of inhibitors of superoxide generation in vascular smooth muscle cells.
abstract: OBJECTIVE
  We compared the dose-dependent reductions in cellular superoxide anion (O(2)(-)) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3',4',5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, alpha-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox).
  
  
  METHODS
  O(2)(-) was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence.
  
  
  RESULTS
  SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O(2)(-) of 80-90%. -Epicatechin, NBT, ebselen and Fe-TTPS were significantly (P < 0.0125) less effective (50-70%), whereas trolox, alpha-tocopherol and ascorbate had little action even over 24 h of incubation (<31%). Effectiveness in disrupted and intact cells was similar for the permeable agents, PEG-SOD and tempol, but was enhanced for SOD. Generation of O(2)(-) was increased by NAC and NBT at low concentrations but reduced at high concentrations.
  
  
  CONCLUSIONS
  Maximum effectiveness against cellular production of O(2)(-) requires cell membrane permeability and catalytic action as exemplified by PEG-SOD or tempol. NAC and NBT have biphasic effects on O(2)(-) production. Vitamins C and E or analogues have low efficacy.
authors.affiliation: Hypertension, Kidney and Vascular Centre, Georgetown University, Washington, DC 20007, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: W J
authors.initials: WJ
authors.lastname: Welch
authors.forename: B T
authors.initials: BT
authors.lastname: Andresen
authors.forename: P A
authors.initials: PA
authors.lastname: Jose
authors.forename: C S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D013481:Superoxides; D013482:Superoxide Dismutase