Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome.
Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome.
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依普利农可恢复患有自发性高血压代谢综合征的恒河猴的 24 小时血压昼夜节律并减少晚期糖基化终产物
DOI：
10.1038/srep23957
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发表时间：
2016-04-01
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
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作者：
Zhang Y;Zheng W;Liu Y;Wang J;Peng Y;Shang H;Hou N;Hu X;Ding Y;Xiao Y;Wang C;Zeng F;Mao J;Zhang J;Ma D;Sun X;Li C;Xiao RP;Zhang X
高血压常与代谢综合征（MetS）相关，是MetS及其并发症的危险因素。高血压患者的血压昼夜节律已被认为有助于高血压的心血管后果和器官损害。但血压昼夜变化及其对药物的反应还没有明确的研究在非人灵长类动物（NHP）的代谢综合征与高血压。在这里，我们从我们的内部队列中确定了16只老年高血压MetS恒河猴。通过植入式遥测，我们研究了血压变化及其昼夜节律，以及降压药物对血压及其昼夜波动的影响。MetS高血压猴表现出较高的血压、肥胖、葡萄糖耐受不良和血脂异常。我们还证实了代谢综合征高血压猴的24小时血压昼夜节律受损。重要的是，依普利酮，盐皮质激素受体阻滞剂，发挥多种有益的影响，在代谢综合征高血压猴，包括血压降低，24小时血压昼夜节律恢复和降低血浆浓度的炎症因子和晚期糖基化终产物。综上所述，我们建立了一个自然发展的高血压MetS NHP模型，这对研究MetS相关高血压的发病机制和开发新的治疗策略具有重要价值。我们还提供了依普利酮对高血压代谢综合征有益作用的多种新机制见解。
Hypertension is often associated with metabolic syndrome (MetS) and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension.