Objective: We sought to determine whether L-arginine polymer treatment of v
ein grafts enhances vascular production of nitric oxide and inhibits the de
velopment of neointimal hyperplasia.
Methods: External jugular veins of New Zealand White rabbits (n = 42) were
harvested; treated intraluminally for 15 minutes with phosphate-buffered sa
line solution or L-arginine polymer 5, 7, or 9 at either 10 or 100 mu mol/L
, and then grafted into the contralateral carotid artery. Rabbits were kill
ed after 28 days, and 5-mum sections of vessels were stained with hematoxyl
in and scored fur intima/media ratio by using computerized morphometric ana
lysis. Separate veins were treated in a similar fashion with biotinylated p
olymers and phosphate-buffered saline solution to assess for translocation
efficiencies. Finally, vein segments pretreated with either phosphate-buffe
red saline solution or L-arginine polymers were cultured in Dulbecco's modi
fied Eagle's medium containing lipopolysaccharide (100 mug/mL) and interfer
on gamma (200 U/mL) for 48 hours before measuring nitric oxide levels by me
ans of the Griess reaction.
Results: Biotinylated L-arginine polymers demonstrated a dose- and length-d
ependent uptake into intimal and medial cells of treated vessels. Nitric ox
ide levels were significantly higher in vein segments treated with 100 mu m
ol/L of L-arginine polymer 9 compared with control segments. Finally, the i
ntima/media ratio also reflected both length- and concentration-dependent i
nhibition of neointimal hyperplasia.
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Conclusions: Arginine polymers of sufficient length and concentration were
effective in increasing nitric oxide levels and reducing neointimal hyperpl
asia in this vein graft model.