Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine.
Hyperlipidemia contributes to the development of intimal hyperplasia and subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine on 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 sacrificed at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until harvest. 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 to norepinephrine, serotonin, and bradykinin were recorded, and following norepinephrine precontraction, relaxation to acetylcholine and sodium nitroprusside were determined. After in situ pressure fixation, intimal 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 grafts contained foam cells and lipid-laden endothelial and smooth muscle cells. There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein grafts were two-fold thicker than in the control group. L-arginine supplementation resulted in the preservation of acetylcholine-mediated relaxation but did not change hypercholesterolemia-induced contractile agonist supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Davies
M G
MG
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Dalen
H
H
Kim
J H
JH
Barber
L
L
Svendsen
E
E
Hagen
P O
PO
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction; D014680:Veins / Q000637:transplantation*
D009569:Nitric Oxide; D001120:Arginine; D002784:Cholesterol