L-arginine polymers inhibit the development of vein graft neointimal hyperplasia.
OBJECTIVE
We sought to determine whether L -arginine polymer treatment of vein grafts enhances vascular production of nitric oxide and inhibits the development of neointimal hyperplasia.


METHODS
External jugular veins of New Zealand White rabbits (n = 42) were harvested; treated intraluminally for 15 minutes with phosphate-buffered saline solution or L -arginine polymer 5, 7, or 9 at either 10 or 100 micromol/L; and then grafted into the contralateral carotid artery. Rabbits were killed after 28 days, and 5-microm sections of vessels were stained with hematoxylin and scored for intima/media ratio by using computerized morphometric analysis. Separate veins were treated in a similar fashion with biotinylated polymers and phosphate-buffered saline solution to assess for translocation efficiencies. Finally, vein segments pretreated with either phosphate-buffered saline solution or L -arginine polymers were cultured in Dulbecco's modified Eagle's medium containing lipopolysaccharide (100 microg/mL) and interferon gamma (200 U/mL) for 48 hours before measuring nitric oxide levels by means of the Griess reaction.


RESULTS
Biotinylated L -arginine polymers demonstrated a dose- and length-dependent uptake into intimal and medial cells of treated vessels. Nitric oxide levels were significantly higher in vein segments treated with 100 micromol/L of L -arginine polymer 9 compared with control segments. Finally, the intima/media ratio also reflected both length- and concentration-dependent inhibition of neointimal hyperplasia.intima/media ratio PBS R5 R7 R9 10 micromol/L 0.909 +/- 0.072 0.920 +/- 0.073 0.861 +/- 0.138 0.710 +/- 0.122 100 micromol/L 0.924 +/- 0.061 0.581 +/- 0.089* 0.529 +/- 0.093* PBS, Phosphate-buffered saline solution; R, L -arginine polymer. *P <.001 versus phosphate-buffered saline solution and L -arginine polymer 5 controls (Bonferroni-corrected value).


CONCLUSIONS
Arginine polymers of sufficient length and concentration were effective in increasing nitric oxide levels and reducing neointimal hyperplasia in this vein graft model.
Kown
M H
MH
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305-5247, USA.
Yamaguchi
A
A
Jahncke
C L
CL
Miniati
D
D
Murata
S
S
Grunenfelder
J
J
Koransky
M L
ML
Rothbard
J B
JB
Robbins
R C
RC
D000818:Animals; D001692:Biological Transport; D019921:Biotinylation; D002339:Carotid Arteries / Q000601:surgery; D006965:Hyperplasia; D007601:Jugular Veins / Q000637:transplantation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology; D014680:Veins / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
D010455:Peptides; C015462:polyarginine; D009569:Nitric Oxide