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EXPERIMENTAL STUDIES

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

^a University and CHRU of Lille, Lille, France

Manuscript received January 12, 1998; revised manuscript received September 21, 1998, accepted November 2, 1998.

Reprint requests and correspondence: Dr. Christophe Bauters, Service de Cardiologie B, Hôpital Cardiologique, Boulevard du Professeur J Leclercq, 59037 Lille Cedex, France

OBJECTIVES

The purpose of this study was to assess the effects of L-arginine and N^G-nitro-L-arginine methyl ester (L-NAME) on neointimal hyperplasia and vascular remodeling after balloon angioplasty in the hypercholesterolemic rabbit.

BACKGROUND

Restenosis after balloon angioplasty is a consequence of both neointimal hyperplasia 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 a 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 area 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 area 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 area circumscribed by the internal elastic lamina (IEL) increased significantly in the control group compared to the acute group (from 2.52 ± 0.66 to 3.33 ± 0.85 mm²); a more marked increase occurred in the L-NAME group (3.90 ± 0.85 mm²). By contrast, IEL area was unchanged in the L-arginine group (2.41 ± 0.62 mm²). As a result, there was no significant difference in lumen area 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 hyperplasia after experimental balloon angioplasty in the hypercholesterolemic rabbit. However, the lack of vessel enlargement in the L-arginine group resulted in a similar final lumen size in the L-NAME and L-arginine groups.

Abbreviations and Acronyms   EEL = external elastic lamina   IEL = internal elastic lamina   ISDN = isosorbide dinitrate   L-NAME = NG-nitro-L-arginine methyl ester   NO = nitric oxide

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