Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet
Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet
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DOI：
10.1161/hypertensionaha.107.099499
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发表时间：
2008-02-01
期刊：
影响因子：
8.3
通讯作者：
Imig, John D.
中科院分区：
文献类型：
--
作者：
Knight, Sarah F.;Quigley, Jeffrey E.;Imig, John D.
肥胖和高血压已被确定为导致终末期肾病进展的心血管危险因素。为了研究高脂饮食和高血压导致内皮功能障碍和肾损伤的机制，8周龄雄性自发性高血压大鼠和Wistar大鼠被喂食高脂（36%脂肪）或正常脂肪（7%脂肪）饮食10周。高脂饮食使Wistar大鼠和高血压大鼠的体重分别增加了25克和31克。与Wistar大鼠相比，高血压大鼠的收缩压较高;然而，高脂饮食对血压没有影响。仅3周后，高脂组的传入小动脉对乙酰胆碱的反应就受损了。高血压高脂组大鼠肾脏巨噬细胞浸润较其他组明显增加，单核细胞趋化蛋白-1分泌在高脂组和高脂组均增加。肾脏PCR阵列显示，2个炎症基因在正常饮食喂养的高血压大鼠中显著增加，1个基因在高脂喂养的Wistar大鼠中增加，而12个基因在高脂喂养的高血压大鼠中增加。与Wistar大鼠相比，高血压大鼠的尿白蛋白排泄量增加，高脂饮食进一步加剧了高血压大鼠的尿白蛋白排泄。高脂饮食可降低高血压大鼠肾小球nephrin表达，增加结蛋白表达。我们的研究结果表明，内皮功能障碍先于肾损伤正常血压和自发性高血压大鼠喂养高脂饮食，高血压与肥胖诱导一个强大的炎症反应和破坏肾滤过屏障。
Obesity and hypertension have been identified as cardiovascular risk factors that contribute to the progression of end-stage renal disease. To examine the mechanisms by which a high-fat diet and hypertension contribute to endothelial dysfunction and renal injury, 8-week-old male spontaneously hypertensive rats and Wistar rats were fed a high-fat (36% fat) or a normal-fat (7% fat) diet for 10 weeks. The high-fat diet increased body weight in Wistar and hypertensive rats by 25 and 31 g, respectively. Systolic blood pressure was higher in the hypertensive rats compared with Wistar rats; however, blood pressure was unaltered by the high-fat diet. Afferent arteriole response to acetylcholine was impaired in the high-fat groups after just 3 weeks. Renal macrophage infiltration was increased in the hypertensive high-fat group compared with others, and monocyte chemoattractant protein-1 excretion was increased in both of the high-fat-fed groups. Renal PCR arrays displayed significant increases in 2 inflammatory genes in hypertensive rats fed a normal diet, 1 gene was increased in high-fat-fed Wistar rats, whereas 12 genes were increased in high-fat-fed hypertensive rats. Urinary albumin excretion was increased in the hypertensive rats compared with the Wistar rats, which was further exacerbated by the high-fat diet. Glomerular nephrin expression was reduced and desmin was increased by the high-fat diet in the hypertensive rats. Our results indicate that endothelial dysfunction precedes renal injury in normotensive and spontaneously hypertensive rats fed a high-fat diet, and hypertension with obesity induces a powerful inflammatory response and disruption of the renal filtration barrier.