Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, 430079, China.
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, 430079, China.
Environ Pollut. 2019 Apr;247:927-934. doi: 10.1016/j.envpol.2019.01.099. Epub 2019 Jan 31.
Epidemiological studies and animal experiments have suggested that exposure to Di-(2-ethylhexyl) phthalate (DEHP) is strongly associated with an increase in blood pressure. However, the mechanisms that result in the detrimental effects of DEHP exposure on blood pressure are unclear. In our study, mice were orally exposed to DEHP dosages of 0.1, 1, 10 mg/kg/day for 6 weeks. The results showed that DEHP could induce a significant increase in systolic blood pressure (SBP) and heart rate, and a significant thickening of the ventricular wall. To explore the underlying mechanism, we measured the level of: angiotensin converting enzyme (ACE); bradykinin B2 receptor (BK2R); endothelial nitric oxide synthase (eNOS); bradykinin and Ca in cardiac cytoplasm as well as in serum nitric oxide (NO). The results suggested that DEHP could induce an increase in ACE levels, and a decrease in bradykinin levels. Moreover, BK2R, Ca, eNOS and NO decreased when mice were exposed to 10 mg/kg/day DEHP. Interestingly, 5 mg/kg/day angiotensin converting enzyme inhibitor (ACEI) treatment inhibited the increase in blood pressure, and inhibited the decrease in the levels of BK2R, Ca, eNOS, and NO, that were induced by DEHP exposure. Our results suggest that DEHP might increase blood pressure by activating ACE expression, and inhibiting the bradykinin-NO pathway.
流行病学研究和动物实验表明，二-(2-乙基己基)邻苯二甲酸酯(DEHP)暴露与血压升高密切相关。然而，导致 DEHP 暴露对血压产生有害影响的机制尚不清楚。在我们的研究中，小鼠经口暴露于 DEHP 的剂量分别为 0.1、1、10mg/kg/天，持续 6 周。结果表明，DEHP 可显著升高收缩压(SBP)和心率，并显著增加心室壁厚度。为了探讨其潜在机制，我们测量了血管紧张素转换酶(ACE)、缓激肽 B2 受体(BK2R)、内皮型一氧化氮合酶(eNOS)、心脏细胞质和血清中缓激肽和 Ca 以及一氧化氮(NO)的水平。结果表明，DEHP 可诱导 ACE 水平升高，缓激肽水平降低。此外，当小鼠暴露于 10mg/kg/天 DEHP 时，BK2R、Ca、eNOS 和 NO 降低。有趣的是，5mg/kg/天血管紧张素转换酶抑制剂(ACEI)治疗可抑制血压升高，并抑制 DEHP 暴露诱导的 BK2R、Ca、eNOS 和 NO 水平降低。我们的结果表明，DEHP 可能通过激活 ACE 表达，抑制缓激肽-NO 途径来升高血压。
