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

OBJECTIVES The purpose of this study was to assess the effects of L-arginin e and NG-nitro-L-arginine methyl ester (L-NAME) on neointimal hyperplasia a nd vascular remodeling after balloon angioplasty in the hypercholesterolemi c rabbit; BACKGROUND Restenosis after balloon angioplasty is a consequence of both ne ointimal hyperplasia and vessel remodeling. Nitric oxide inhibits neointima l hyperplasia, but its effect on vessel remodeling is unknown. METHODS Six weeks after induction of bilateral iliac atherosclerosis, 48 ra bbits 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 a diet supplemented wi th either L-arginine (1.5 g/kg/day), or L-NAME (15 mg/kg/day) for 4 weeks a fter angioplasty. RESULTS The intimal area was significantly greater in the chronic control g roup compared to the acute group (2.60 +/- 1.03 mm(2) vs. 1.35 +/- 0.62 mm( 2)). This increase in intimal area was lower in the L-arginine group (1.79 +/- 0.61 mm(2)), and greater in the L-NAME group (3.23 +/- 0.92 mm(2)). The area circumscribed by the internal elastic lamina (IEL) increased signific antly in the control group compared to the acute group (from 2.52 +/- 0.66 to 3.33 +/- 0.85 mm(2)); a more marked increase occurred in the L-NAME grou p (3.90 +/- 0.85 mm(2)). By contrast; IEL area was unchanged in the L-argin ine group (2.41 +/- 0.62 mm(2)). As a result, there was no significant diff erence in lumen area after 4 weeks in the chronic groups (control: 0.74 +/- 0.38 mm(2); L-arginine: 0.50 +/- 0.43 mm(2); L-NAME: 0.48 +/- 0.42 mm(2)). CONCLUSIONS Our results demonstrate that L-arginine inhibits whereas L-NAME stimulates neointimal hyperplasia after experimental balloon angioplasty i n the hypercholesterolemic rabbit. However, the lack of vessel enlargement in the L-arginine group resulted in a similar final lumen size in the L-NAM E and L-arginine groups. (C) 1999 by the American College of Cardiology.