CHRONIC INHIBITION OF NITRIC-OXIDE PRODUCTION ACCELERATES NEOINTIMA FORMATION AND IMPAIRS ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLEMIC RABBITS
CHRONIC INHIBITION OF NITRIC-OXIDE PRODUCTION ACCELERATES NEOINTIMA FORMATION AND IMPAIRS ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLEMIC RABBITS
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DOI：
10.1161/01.atv.14.5.753
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发表时间：
1994-05-01
期刊：
影响因子：
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通讯作者：
COHEN, RA
中科院分区：
文献类型：
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作者：
CAYATTE, AJ;PALACINO, JJ;COHEN, RA
为了确定内源性局部水平的一氧化氮（NO）是否调节动脉粥样硬化，我们研究了用n - g -硝基- l-精氨酸甲酯（L-NAME）抑制NO对胆固醇喂养家兔早期新内膜形成的影响。雄性家兔连续5周单独饲喂0.5%胆固醇饲粮，后4周通过渗透微型泵添加L-NAME （12 mg/kg / d SC）。通过血管反应性和环GMP水平评估离体主动脉环内皮细胞功能。在l - name处理的家兔中，乙酰胆碱对乙酰胆碱和钙离子载体A23187的内皮依赖性松弛有抑制作用，同时乙酰胆碱对环GMP积累有损害。通过计算机图像分析确定中膜和内膜横截面积来评估胸升主动脉的新生内膜形成。与单独食用胆固醇饲料的家兔相比，l - name处理的家兔病变面积（0.29+/-0.04 mm比0.15+/-0.03 mm(2)）和病变/介质比（0.06+/-0.01比0.03+/-0.01）显著增加。血浆胆固醇和荧光脂质过氧化产物水平不变，表明胆固醇代谢或氧化没有差异。由于L-NAME治疗没有改变动脉血压，因此动脉粥样硬化的增加不能归因于血压的升高。这些结果表明，局部抑制NO加速早期内膜形成可能是由于调节单核细胞募集或泡沫细胞脂质积累。
To determine if endogenous local levels of nitric oxide (NO) modulate atherogenesis, we studied the effect of inhibiting NO with N-G-nitro-L-arginine methyl ester (L-NAME) on early neointima formation in cholesterol-fed rabbits. Male rabbits were fed for 5 weeks with a 0.5% cholesterol diet alone or treated in addition during the last 4 weeks with L-NAME (12 mg/kg per day SC) via osmotic minipump. Endothelial cell function was assessed in isolated aortic rings by vascular reactivity and levels of cyclic GMP. In L-NAME-treated rabbits there was inhibition of endothelium-dependent relaxations to acetylcholine and the calcium ionophore A23187 as well as impaired cyclic GMP accumulation in response to acetylcholine. Neointima formation in the ascending thoracic aorta was assessed by determining media and intima cross-sectional areas with computerized image analysis. Compared with rabbits that consumed the cholesterol diet alone, L-NAME-treated rabbits had significant increases in lesion area (0.29+/-0.04 versus 0.15+/-0.03 mm(2)) and in lesion/ media ratio (0.06+/-0.01 versus 0.03+/-0.01). Plasma levels of cholesterol and fluorescent lipid peroxide products were unchanged, suggesting no difference in cholesterol metabolism or oxidation. Because arterial blood pressure was not altered by L-NAME treatment, the increased atherogenesis could not be attributed to an increase in blood pressure. These results indicated that local inhibition of NO accelerates early neointima formation possibly because of modulating monocyte recruitment or foam cell lipid accumulation.