Hypercholesterolemia Impairs Nonstenotic Kidney Outcomes After Reversal of Experimental Renovascular Hypertension.
Hypercholesterolemia Impairs Nonstenotic Kidney Outcomes After Reversal of Experimental Renovascular Hypertension.
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DOI：
10.1093/ajh/hpv222
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发表时间：
2016-07
影响因子：
3.2
通讯作者：
Dong Sun;Zhi Chen;A. Eirin;Xiang-yang Zhu;A. Lerman;S. Textor;L. Lerman
中科院分区：
文献类型：
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作者：
Dong Sun;Zhi Chen;A. Eirin;Xiang-yang Zhu;A. Lerman;S. Textor;L. Lerman
背景狭窄肾动脉血运重建仅在动脉粥样硬化继发的肾血管性高血压(HT)患者中改善肾功能。然而，逆转肾血管性高血压(RRHT)对非狭窄肾脏的影响尚不清楚。我们假设并发高胆固醇血症(HC)会削弱非狭窄肾脏的恢复。方法雌性家猪随机分为正常组、肾血管性高血压组、高血压+RRHT组、HTC组(肾血管性高血压和HC)、HTC+RHT组(n=7)。术后6周分别行RRHT或SHAM。4周后对非狭窄肾血流、肾小球滤过率和损伤途径进行研究。结果HTC组和HTC组平均动脉压升高相似，RRHT组平均动脉压降低。氧化应激在HTC和HTC肾脏中升高，在HTC+RRHT中降低，但在HTC+RRHT中保持升高。肾间质纤维化、肾小球硬化和肾小管损伤在HTC+RRHT组均有减轻，但HTC+RRHT组未见改善。HTC和HTC+RRHT型猪的内皮素-1信号转导和PGF2α异前列腺素水平均升高。结论RRHT可逆转实验性肾血管性HT的非狭窄肾损伤，但合并HC可钝化肾损伤的消退，这可能是由于主要的血管收缩物质和氧化应激所致。这些发现强化了非狭窄肾脏和普遍的心血管危险因素在血运重建后肾功能障碍不可逆性中的作用。
BACKGROUND Revascularization of a stenotic renal artery improves kidney function only in select patients with renovascular hypertension (HT) secondary to atherosclerosis. However, the effects of reversal of renovascular HT (RRHT) on the nonstenotic kidney are unclear. We hypothesized that concurrent hypercholesterolemia (HC) attenuates nonstenotic kidney recovery. METHODS Female domestic pigs were randomized as Normal, renovascular HT, HT+RRHT, HTC (renovascular HT and HC), and HTC+RHT (n = 7 each). RRHT or sham was performed after 6 weeks of HT. Nonstenotic renal blood flow, glomerular filtration rate, and injurious pathways were studied 4 weeks later. RESULTS Mean arterial pressure increased similarly in HT and HTC and decreased after RRHT. Oxidative stress increased in HT and HTC kidneys, and decreased in HT+RRHT, but remained elevated in HTC+RRHT. Renal interstitial fibrosis, glomerulosclerosis, and tubular injury were all attenuated in HT+RRHT, but not HTC+RRHT. Endothelin-1 signaling and PGF2α isoprostane levels were elevated in both HTC and HTC+RRHT pigs. CONCLUSIONS RRHT reverses nonstenotic kidney injury in experimental renovascular HT, but concurrent HC blunts regression of kidney injury, possibly due to predominant vasoconstrictors and oxidative stress. These findings reinforce the contribution of the nonstenotic kidney and of prevailing cardiovascular risk factors to irreversibility of kidney dysfunction after revascularization.