Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasi and vascular remodeling

OBJECTIVES The purpose of this study was to assess the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on neointimal hyperplasi and vascular remodeling after balloon angioplasty in the hypercholesterolemic rabbit. BACKGROUND Restenosis after balloon angioplasty is consequence of both neointimal hyperplasi and vessel remodeling. Nitric oxide inhibits neointimal hyperplasia, but its effect on vessel remodeling is unknown. METHODS Six weeks after induction of bilateral iliac atherosclerosis, 48 rabbits underwent successful angioplasty in 75 vessels. Eight rabbits (acute group) were sacrificed immediately after angioplasty. The remaining animals received either placebo (chronic control group), or diet supplemented with either L-arginine (1.5 g/kg/day), or L-NAME (15 mg/kg/day) for 4 weeks after angioplasty. RESULTS The intimal are was significantly greater in the chronic control group compared to the acute group (2.60 ± 1.03 mm2 vs. 1.35 ± 0.62 mm2). This increase in intimal are was lower in the L-arginine group (1.79 ± 0.61 mm2), and greater in the L-NAME group (3.23 ± 0.92 mm2). The are circumscribed by the internal elastic lamin (IEL) increased significantly in the control group compared to the acute group (from 2.52 ± 0.66 to 3.33 ± 0.85 mm2); more marked increase occurred in the L-NAME group (3.90 ± 0.85 mm2). By contrast, IEL are was unchanged in the L-arginine group (2.41 ± 0.62 mm2). As result, there was no significant difference in lumen are after 4 weeks in the chronic groups (control: 0.74 ± 0.38 mm2; L-arginine: 0.50 ± 0.43 mm2; L-NAME: 0.48 ± 0.42 mm2). CONCLUSIONS Our results demonstrate that L-arginine inhibits whereas L-NAME stimulates neointimal hyperplasi after experimental balloon angioplasty in the hypercholesterolemic rabbit. However, the lack of vessel enlargement in the L-arginine group resulted in similar final lumen size in the L-NAME and L-arginine groups.