Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.
Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.
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DOI：
10.1289/ehp164
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发表时间：
2016-11
影响因子：
10.4
通讯作者：
Buettner C
中科院分区：
文献类型：
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作者：
La Merrill MA;Sethi S;Benard L;Moshier E;Haraldsson B;Buettner C
二氯二苯三氯乙烷（DDT）在世界范围内被广泛用于控制疟疾、斑疹伤寒、体虱和黑死病，直到20世纪70年代各国开始限制其使用。然而，发展中国家继续使用滴滴涕来控制病媒传播的疾病。产前接触滴滴涕与人类血压升高有关。我们假设围产期DDT暴露会导致成年小鼠高血压。从妊娠第11.5天至出生后第5天，对C57BL/6J进行滴滴涕治疗。测定雄性和雌性成年后代的血压和心肌壁厚度。用血管紧张素转换酶（ACE）抑制剂卡托普利治疗成年小鼠，以评估ACE抑制对ddt相关性高血压的改善敏感性。我们进一步评估了DDT暴露对通过肾离子转运调节血压的mrna表达的影响。围产期暴露于DDT的成年小鼠表现出慢性收缩压升高、心肌壁厚度增加和几种肾离子转运蛋白mrna表达升高。卡托普利完全逆转了围产期暴露于DDT的小鼠的高血压。这些数据表明，围产期接触滴滴涕会导致成年后代高血压和心脏肥厚。高血压的一个关键机制是肾素血管紧张素系统过度激活，因为ACE抑制逆转了围产期DDT暴露引起的高血压。刘建军，刘建军，刘建军，刘建军。2016。围产期DDT暴露可诱导成年小鼠高血压和心脏肥厚。环境卫生展望124:1722-1727；http://dx.doi.org/10.1289/EHP164
Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722–1727; http://dx.doi.org/10.1289/EHP164