Comparison of inhibitors of superoxide generation in vascular smooth muscle cells.
Br J Pharmacol
; 157(6): 935-43, 2009 Jul.
Article
in En
| MEDLINE
| ID: mdl-19466991
ABSTRACT
BACKGROUND AND PURPOSE:
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). EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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 AND IMPLICATIONS 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Superoxides
/
Myocytes, Smooth Muscle
/
Muscle, Smooth, Vascular
Limits:
Animals
Language:
En
Journal:
Br J Pharmacol
Year:
2009
Document type:
Article
Affiliation country:
United States