L-ARGININE INHIBITS SMOOTH-MUSCLE CELL-PROLIFERATION OF VEIN GRAFT INTIMAL THICKNESS IN HYPERCHOLESTEROLEMIC RABBITS

Objective: The effect of the chronic administration of L-arginine on i ntimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined. Meth ods: Male rabbits were fed a 1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water (arginine group). Each group underwent reversed autologous vein bypass grafting of the left common carotid artery using the left exter nal jugular vein. At 2 or 4 weeks after operation, intimal cell prolif eration was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytome ter. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording. Results: At 4 weeks after ope ration, the level of plasma arginine and citrulline are significantly higher in the arginine group (n = 7), compared with the control (n = 7 ). Intimal thickness in the arginine group (n = 7) was significantly r educed, compared with that of the control (n = 7). At 2 weeks after op eration, the BrdU labeling index of the control (n = 5) was significan tly higher than that of the arginine group (n = 5). At 4 weeks after o peration, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax. Conclu sions: These results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at a n early stage after graft implantation, prior to the development of in timal thickness. Intimal thickness of vein graft during hypercholester olemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO pr oduction in the blood vessel wall may therefore be useful for preventi ng late graft failure. (C) 1997 Elsevier Science B.V.