一氧化氮在高胆固醇血症兔实验性球囊血管成形术后再狭窄中的作用：对内膜增生和血管重塑的影响。

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

作者信息

Le Tourneau T, Van Belle E, Corseaux D, Vallet B, Lebuffe G, Dupuis B, Lablanche J M, McFadden E, Bauters C, Bertrand M E

机构信息

University and CHRU of Lille, France.

出版信息

J Am Coll Cardiol. 1999 Mar;33(3):876-82. doi: 10.1016/s0735-1097(98)00621-4.

DOI:10.1016/s0735-1097(98)00621-4

PMID:10080493

Abstract

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.

摘要

目的

本研究旨在评估L-精氨酸和N(G)-硝基-L-精氨酸甲酯（L-NAME）对高胆固醇血症兔球囊血管成形术后内膜增生和血管重塑的影响。

背景

球囊血管成形术后再狭窄是内膜增生和血管重塑共同作用的结果。一氧化氮可抑制内膜增生，但其对血管重塑的影响尚不清楚。

方法

在诱导双侧髂动脉粥样硬化6周后，48只兔子的75条血管成功进行了血管成形术。8只兔子（急性组）在血管成形术后立即处死。其余动物在血管成形术后接受安慰剂（慢性对照组），或补充L-精氨酸（1.5 g/kg/天）或L-NAME（15 mg/kg/天）的饮食，持续4周。

结果

与急性组相比，慢性对照组的内膜面积显著更大（2.60±1.03 mm2对1.35±0.62 mm2）。L-精氨酸组内膜面积的增加较低（1.79±0.61 mm2），而L-NAME组更大（3.23±0.92 mm2）。与急性组相比，对照组中内弹性膜（IEL）所包围的面积显著增加（从2.52±0.66增加到3.33±0.85 mm2）；L-NAME组增加更为明显（3.90±0.85 mm2）。相比之下，L-精氨酸组的IEL面积未改变（2.41±0.62 mm2）。因此，慢性组在4周后的管腔面积无显著差异（对照组：0.74±0.38 mm2；L-精氨酸组：0.50±0.43 mm2；L-NAME组：0.48±0.42 mm2）。