Mg. Davies et al., REDUCTION OF EXPERIMENTAL VEIN GRAFT INTIMAL HYPERPLASIA AND PRESERVATION OF NITRIC OXIDE-MEDIATED RELAXATION BY THE NITRIC-OXIDE PRECURSORL-ARGININE, Surgery, 116(3), 1994, pp. 557-568
Background. Previous studies in animals and human beings have shown th
at vein bypass grafts exhibit diminished endothelium-dependent relaxat
ion and the development of intimal hyperplasia. This study examines th
e effect of L-arginine on experimental vein graft endothelial cell fun
ction and the development of intimal hyperplasia. Methods. Common caro
tid vein bypass grafts were performed in 24 New Zealand White rabbits:
12 were controls and 12 received L-arginine (2.25%) orally 7 days bef
ore operation and thereafter until harvest 28 days after operation. In
timal and medial dimensions were determined by planimetry on pressure-
fixed vessels. Relaxation to acetylcholine, serotonin, calcium ionopho
re (A23187), and sodium nitroprusside was performed on precontracted v
essel rings. Results. Arginine-treated vein grafts showed a 47% reduct
ion in mean intimal thickness (p < 0.001) compared with controls. By s
canning and transmission electron microscopy, all vein grafts showed a
confluent endothelium. In contrast to control grafts, which do not re
lax to acetylcholine and serotonin, arginine-treated vein grafts relax
ed in response to both agonists. There was a significant increase (P <
0.05) in the maximal relaxation to calcium ionophore (A23187) in argi
nine-treated vein grafts compared with control grafts. Non-endothelium
-dependent responses to sodium nitroprusside were equivalent in all ve
in grafts. Conclusions. This study shows that oral L-arginine suppleme
ntation significantly reduces intimal hyperplasia and preserves nitric
oxide-mediated relaxation in experimental vein grafts, suggesting a r
ole for nitric oxide in the regulation of the cellular events that lea
d to intimal hyperplasia.