REDUCTION OF EXPERIMENTAL VEIN GRAFT INTIMAL HYPERPLASIA AND PRESERVATION OF NITRIC OXIDE-MEDIATED RELAXATION BY THE NITRIC-OXIDE PRECURSORL-ARGININE

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.