Reduction of experimental vein graft intimal hyperplasia and preservation of nitric oxide-mediated relaxation by the nitric oxide precursor L-arginine.
BACKGROUND
Previous studies in animals and human beings have shown that vein bypass grafts exhibit diminished endothelium-dependent relaxation and the development of intimal hyperplasia. This study examines the effect of L-arginine on experimental vein graft endothelial cell function and the development of intimal hyperplasia.


METHODS
Common carotid vein bypass grafts were performed in 24 New Zealand White rabbits: 12 were controls and 12 received L-arginine (2.25%) orally 7 days before operation and thereafter until harvest 28 days after operation. Intimal and medial dimensions were determined by planimetry on pressure-fixed vessels. Relaxation to acetylcholine, serotonin, calcium ionophore (A23187), and sodium nitroprusside was performed on precontracted vessel rings.


RESULTS
Arginine-treated vein grafts showed a 47% reduction in mean intimal thickness (p < 0.001) compared with controls. By scanning and transmission electron microscopy, all vein grafts showed a confluent endothelium. In contrast to control grafts, which do not relax to acetylcholine and serotonin, arginine-treated vein grafts relaxed in response to both agonists. There was a significant increase (p < 0.05) in the maximal relaxation to calcium ionophore (A23187) in arginine-treated vein grafts compared with control grafts. Non-endothelium-dependent responses to sodium nitroprusside were equivalent in all vein grafts.


CONCLUSIONS
This study shows that oral L-arginine supplementation significantly reduces intimal hyperplasia and preserves nitric oxide-mediated relaxation in experimental vein grafts, suggesting a role for nitric oxide in the regulation of the cellular events that lead to intimal hyperplasia.
Davies
M G
MG
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710.
Kim
J H
JH
Dalen
H
H
Makhoul
R G
RG
Svendsen
E
E
Hagen
P O
PO
D000818:Animals; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D017536:Carotid Artery, Common / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D006083:Graft Occlusion, Vascular / Q000503:physiopathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000188:drug therapy; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D009569:Nitric Oxide; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine