Characterization of a Model of an Arteriovenous Fistula in the Rat The Effect of L-NAME

被引:50
作者
Croatt, Anthony J. [1 ]
Grande, Joseph P. [1 ,2 ]
Hernandez, Melissa C. [1 ]
Ackerman, Allan W. [1 ]
Katusic, Zvonimir S. [3 ,4 ]
Nath, Karl A. [1 ]
机构
[1] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Anesthesiol, Rochester, MN 55905 USA
[4] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
基金
美国国家卫生研究院;
关键词
NITRIC-OXIDE SYNTHASE; CHRONIC KIDNEY-DISEASE; INDUCED ARTERIAL ENLARGEMENT; ACTIVITY IN-VIVO; HEMODIALYSIS-PATIENTS; INTIMAL HYPERPLASIA; HEME OXYGENASE-1; SMOOTH-MUSCLE; ASYMMETRIC DIMETHYLARGININE; NEOINTIMAL HYPERPLASIA;
D O I
10.2353/ajpath.2010.090649
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Vascular access dysfunction contributes to the mortality of patients undergoing chronic hemodialysis. The present study analyzed the changes that evolve in a femoral arteriovenous fistula in the rat. The venous segment of this model exhibited, at 1 week, activation of pro-inflammatory transcription factors and up-regulation of pro-inflammatory, proliferative, procoagulant, and profibrotic genes; and at 4 weeks, the venous segment displayed neointimal hyperplasia, smooth muscle proliferation, and thrombus formation. These changes were accompanied by endothelial (e) nitric oxide synthase (NOS) and inducible (i) NOS up-regulation. The administration of N-G-nitro-L-arginine methyl ester, an inhibitor of NOS activity, increased venous neointimal hyperplasia and pro-inflammatory gene expression (monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1), increased systolic blood pressure, and decreased blood flow through the fistula. In another hypertensive model, the rat subtotal nephrectomy model, venous neointimal hyperplasia in the arteriovenous fistula was also exacerbated. We conclude that this arteriovenous fistula model recapitulates the salient features observed in dysfunctional, hemodialysis arteriovenous fistulas, and that venous neointimal hyperplasia is exacerbated when this model is superimposed in two different models of systemic hypertension. Since the uremic milieu contains increased amounts of asymmetric dimethylarginine, we speculate that such accumulation of this endogenous inhibitor of NOS, by virtue of its pressor or nitric oxide-depleting effects, or a combination thereof, may contribute to the limited longevity of arteriovenous fistulas used for hemodialysis. (Am J Pathol 2010, 176:2530-2541; DOI: 10.2353/ajpath.2010.090649)
引用
收藏
页码:2530 / 2541
页数:12
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