CONTROL OF ACCELERATED VEIN GRAFT ATHEROMA WITH THE NITRIC-OXIDE PRECURSOR L-ARGININE

Hyperlipidemia contributes to the development of intimal hyperplasia a nd subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine o n the development of intimal hyperplasia and the vasomotor function of vein grafts in hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were sacrifice d at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until h arvest. Of these, 10 also received L-arginine (2.25%, 2 g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10 animals were controls, Vein grafts were harvested either for morphology or for in vitro isometric tension studies. Cumulative dose-response curves t o norepinephrine, serotonin, and bradykinin were recorded, and followi ng norepinephrine precontraction, relaxation to acetylcholine and sodi um nitroprusside were determined. After in situ pressure fixation, int imal thicknesses of the vein grafts were measured by videomorphometry. The addition of L-arginine doubled the serum arginine concentrations, Intimal hyperplasia of both groups of hypercholesterolemic vein graft s contained foam cells and lipid-laden endothelial and smooth muscle c ells, There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the h ypercholesterolemia group (P < 0.05). All hypercholesterolemic vein gr afts were two-fold thicker than in the control group, L-arginine suppl ementation resulted in the preservation of acetylcholine-mediated rela xation but did not change hypercholesterolemia-induced contractile ago nist supersensitivity. Therefore, L-arginine supplementation can slow the formation of atheromatous intimal hyperplasia in vein grafts; it c an improve endothelial cell function but it does not prevent the persi stence of the hypercholesterolemia-associated smooth muscle phenotype. (C) 1995 Academic Press, Inc.