Correlation of changes in nitric oxide synthase, superoxide dismutase and nitrotyrosine with endothelial regeneration and neointimal hyperplasia in the balloon-injured rabbit subclavian artery.
OBJECTIVE
Alterations in nitric oxide (NO) and superoxide production within the wall of injured vessels may modulate the development and eventual extent of neointima after balloon injury.


METHODS
In this study we have characterized a rabbit model of subclavian artery injury and have used immunocytochemistry to detect NO synthase (NOS) isoforms, Cu-Zn superoxide dismutase (SOD) and nitrotyrosine in the injured vessel from 2 h to 28 days after injury.


RESULTS
At 48 h after injury, when cellular proliferation that will ultimately form the neointima is commencing, there was upregulation of inducible NOS, Cu-Zn SOD and nitrotyrosine. Recovery of endothelial NOS occurred at 28 days after injury, when the neointima is stabilizing and cellular proliferation has slowed down. There was no increase in neuronal NOS at any time point studied.


CONCLUSIONS
NO may serve to limit the development of neointima while superoxide may attenuate the effect of NO by formation of peroxynitrite, detected as increased nitrotyrosine staining. Upregulation of Cu-Zn SOD would limit superoxide both at sites of inflammation in the vessel wall from 48 h and in the adventitia up to 28 days after injury. Very early intervention to protect NO may reduce neointimal size.
Kennedy
Simon
S
Department of Physiology and Pharmacology, University of Strathclyde; Department of Pathology, Glasgow Royal Infirmary, Glasgow, UK. simon.kennedy@strath.ac.uk
Preston
Anthony A
AA
McPhaden
Allan R
AR
Miller
Ashley M
AM
Wainwright
Cherry L
CL
Wadsworth
Roger M
RM
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011817:Rabbits; D012038:Regeneration / Q000502:physiology; D013348:Subclavian Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis*
C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase