Vinegar decreases blood pressure by down-regulating AT1R expression via the AMPK/PGC-1α/PPARγ pathway in spontaneously hypertensive rats
Vinegar decreases blood pressure by down-regulating AT1R expression via the AMPK/PGC-1α/PPARγ pathway in spontaneously hypertensive rats
复制标题
醋通过 AMPK/PGC-1α/PPARγ 途径下调自发性高血压大鼠 AT1R 表达来降低血压
DOI：
10.1007/s00394-015-0937-7
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发表时间：
2016-04-01
影响因子：
5
通讯作者：
Sun, Changhao
中科院分区：
文献类型：
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作者：
Na, Lixin;Chu, Xia;Sun, Changhao
据报道，醋可降低血压，但其作用机制尚不清楚。本研究探讨醋是否通过激活腺苷酸活化蛋白激酶（AMPK）通路发挥降压作用。将雄性自发性高血压大鼠（SHRs）分为醋组、乙酸组、硝苯地平组、硝苯地平 + 醋组或蒸馏水组，通过灌胃给药8周。对血液和主动脉进行生化指标及蛋白质表达水平分析。用不同剂量的乙酸处理猿病毒40转化的大鼠主动脉内皮细胞系（SVAREC）细胞24小时；评估蛋白质表达水平。在第6周和第8周时，醋和乙酸可降低SHRs的血压，且硝苯地平 + 醋组在血压控制方面比单独使用醋或硝苯地平效果更好。醋和乙酸可降低SHRs血清肾素和血管紧张素转换酶（ACE）活性以及血管紧张素II和醛固酮浓度。醋和乙酸还可提高SHRs的AMP/ATP比值以及pAMPK、过氧化物酶体增殖物激活受体γ辅激活因子 - 1α（PGC - 1α）和过氧化物酶体增殖物激活受体γ（PPARγ）的表达水平，同时抑制血管紧张素II 1型受体（AT1R）的表达。在200或400 μmol/L乙酸处理的SVAREC细胞中也发现了这些蛋白质表达的变化。在存在AMPK抑制剂或PGC - 1α小干扰RNA的情况下，乙酸对SVAREC细胞下游蛋白质表达的影响分别被消除。醋通过提高AMP/ATP比值激活AMPK，从而提高SHRs中PGC - 1α和PPARγ的表达，并抑制AT1R的表达。乙酸是醋发挥降压作用的原因。醋和硝苯地平在血压控制方面存在协同作用。
PurposeVinegar has been reported to lower blood pressure, but its mechanism is unclear. This study explored whether vinegar plays antihypertensive effect by activating AMP-activated protein kinase (AMPK) pathway.MethodsMale spontaneously hypertensive rats (SHRs) were assigned to vinegar, acetic acid, nifedipine, nifedipine + vinegar, or distilled water by oral gavage for 8 weeks. Blood and aortas were analyzed for biochemical indices and protein expression levels. Sv40-transformed aortic rat endothelia cell line (SVAREC) cells were treated with acetate at different doses for 24 h; protein expression levels were assessed.ResultsVinegar and acetic acid decreased blood pressure in SHRs on weeks 6 and 8, and nifedipine + vinegar had a better effect on blood pressure control than vinegar or nifedipine alone. Vinegar and acetic acid could decrease serum renin and angiotensin-converting enzyme (ACE) activities, angiotensin II and aldosterone concentrations in SHRs. Vinegar and acetic acid also increased AMP/ATP ratios and expression levels of pAMPK, PPARγ coactivator-1α (PGC-1α), and PPARγ while inhibited angiotensin II type 1 receptor (AT1R) expression in SHRs. The changes in these protein expressions were also found in SVAREC cells treated with 200 or 400 μmol/L acetate. In the presence of AMPK inhibitor or PGC-1α small interfering RNA, the effects of acetate on their downstream protein expression in SVAREC cells were abolished, respectively.ConclusionVinegar activates AMPK by increasing AMP/ATP ratios, thereby increases PGC-1α and PPARγ expressions, and inhibits AT1R expression in SHRs. Acetic acid is responsible for the antihypertensive effects of vinegar. There is a joint effect between vinegar and nifedipine in blood pressure control.