Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits.
OBJECTIVE
The redox pathophysiology of vascular repair is incompletely understood. We assessed the role of vascular superoxide dismutase (SOD) activity in oxidative/nitrative stress and caliber loss postinjury (PI).


RESULTS
Rabbits submitted to iliac artery balloon overdistension were followed for 14 days PI. Significant decrease in vascular SOD activity occurred at 7 and 14 days PI (by 45% and 34%, respectively, versus control, 96+/-1 U/mg, P<0.05). Separation in concanavalin-A column showed that both extracellular SOD (ecSOD) and CuZn SOD activities were reduced, whereas Western analysis showed normal or augmented protein expression. Immunoreactivity to nitrotyrosine, neuronal NO synthase (NOS), and inducible NOS (iNOS) increased in media and neointima PI; iNOS mRNA also augmented. Administration of ecSOD from days 7 to 14 PI corrected the SOD activity decrease and minimized caliber loss by 59% (P=0.007) despite unaltered neointima. Nitrate levels markedly increased with ecSOD in injured artery homogenates (26+/-5 versus 4+/-0.3 micromol/L per mg, P=0.001). Such increase was 70% inhibited by specific iNOS antagonist 1400w. Nitrotyrosine and neuronal NOS expression decreased after ecSOD.


CONCLUSIONS
Sustained low vascular SOD activity has a key role in constrictive remodeling after injury, promoting oxidative/nitrative stress and impairment of iNOS-derived NO bioavailability. SOD function may critically determine whether iNOS induction is beneficial or deleterious in vivo.
Leite
Paulo F
PF
Vascular Biology Laboratory, Heart Institute, University of São Paulo School of Medicine, Av. Enéas de Carvalho Aguiar, 44, subsolo, CEP 05403-000 São Paulo, Brazil.
Danilovic
Alexandre
A
Moriel
Patricia
P
Dantas
Katia
K
Marklund
Stefan
S
Dantas
Ana Paula V
AP
Laurindo
Francisco R M
FR
D000818:Animals; D002404:Catheterization / Q000379:methods*; D003251:Constriction, Pathologic / Q000201:enzymology* / Q000378:metabolism; D004108:Dilatation, Pathologic / Q000201:enzymology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007083:Iliac Artery / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology; D017540:Tunica Media / Q000737:chemistry / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism
D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase