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 intimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined.


METHODS
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 external jugular vein. At 2 or 4 weeks after operation, intimal cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording.


RESULTS
At 4 weeks after operation, 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 reduced, compared with that of the control (n = 7). At 2 weeks after operation, the BrdU labeling index of the control (n = 5) was significantly higher than that of the arginine group (n = 5). At 4 weeks after operation, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax.


CONCLUSIONS
These results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at an early stage after graft implantation, prior to the development of intimal thickness. Intimal thickness of vein graft during hypercholesterolemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO production in the blood vessel wall may therefore be useful for preventing late graft failure.
Okazaki
J
J
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Komori
K
K
Kawasaki
K
K
Eguchi
D
D
Ishida
M
M
Sugimachi
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002956:Citrulline / Q000097:blood; D006084:Graft Rejection / Q000517:prevention & control; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology*; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D001973:Bromodeoxyuridine; D000109:Acetylcholine; D009638:Norepinephrine