Diet-induced hyperhomocysteinemia impairs vasodilation in 5/6-nephrectomized rats
Diet-induced hyperhomocysteinemia impairs vasodilation in 5/6-nephrectomized rats
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饮食引起的高同型半胱氨酸血症损害 5/6 肾切除大鼠的血管舒张
DOI：
10.1007/s00726-018-2626-3
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发表时间：
2018-10-01
期刊：
影响因子：
3.5
通讯作者：
Ichida, Kimiyoshi
中科院分区：
文献类型：
--
作者：
Li, Lei;Hasegawa, Hiroshi;Ichida, Kimiyoshi
血浆同型半胱氨酸在肾功能受损患者中升高，在终末期肾脏疾病中尤其明显。由于慢性肾脏疾病和高同型半胱氨酸血症也是心血管疾病的独立危险因素，后者被认为会加速肾功能衰竭后的血管异常。本研究旨在探讨肾功能受损和高同型半胱氨酸血症对血管功能的影响。我们发现，在5/6肾切除的慢性肾脏疾病模型大鼠中，富含蛋氨酸的饮食8周可诱导中度高同型半胱氨酸血症，加重高血压，并减弱血管对乙酰胆碱、硝普钠、8-溴- cgmp和异丙肾上腺素的反应。血浆硝酸盐/亚硝酸盐和胸主动脉总NOS活性不受影响。总的来说，这些数据表明，高同型半胱氨酸血症和终末期肾病通过阻断cGMP/蛋白激酶G和/或cAMP/蛋白激酶A通路，协同损害内皮依赖性和内皮非依赖性血管舒张。5/6-富蛋氨酸饮食诱导的高同型半胱氨酸血症肾切除大鼠可能是阐明终末期肾病患者血管损伤发病机制的有用模型。
Plasma homocysteine is elevated in patients with impaired renal function, and markedly so at end-stage renal disease. As chronic kidney disease and hyperhomocysteinemia are also independent risk factors for cardiovascular disease, the latter is hypothesized to accelerate vascular abnormalities following renal failure. This study aimed to investigate the combined effect of impaired renal function and hyperhomocysteinemia on vascular function. We show that in 5/6-nephrectomized rats, a model of chronic kidney disease, a methionine-rich diet for 8 weeks induces moderate hyperhomocysteinemia, exacerbates hypertension, and attenuates the vascular response to acetylcholine, sodium nitroprusside, 8-bromo-cGMP, and isoprenaline. However, plasma nitrate/nitrite and total NOS activity in the thoracic aorta were not affected. Collectively, the data imply that hyperhomocysteinemia and end-stage renal disease synergistically impair endothelium-dependent and endothelium-independent vasodilatation by blocking the cGMP/protein kinase G and/or cAMP/protein kinase A pathways. 5/6-Nephrectomized rat with hyperhomocysteinemia induced by a methionine-rich diet would be a useful model for elucidating the pathogenesis of vascular impairment in patients with end-stage renal disease.