Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice

• Published in: Environmental health perspectives 2016-11, Vol.124 (11), p.1722-1727
• Main Authors: La Merrill, Michele A, Sethi, Sunjay, Benard, Ludovic, Moshier, Erin, Haraldsson, Borje, Buettner, Christoph
• Format: Article
• Language: English
• Subjects: 8-tetrachlorodibenzo-p-dioxin; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; association; beta-cells; Blood Pressure; Captopril - therapeutic use; Cardiac and Cardiovascular Systems; Cardiomegaly - chemically induced; cardiovascular-disease; DDT (Insecticide); DDT - toxicity; Environmental & Occupational; Environmental Exposure; Environmental Health and Occupational Health; Environmental Sciences & Ecology; Farmakologi och toxikologi; Female; fetal; gene-expression; growth; Health; Heart enlargement; Hypertension; Hypertension - chemically induced; Kardiologi; Male; Mice; Mice, Inbred C57BL; Miljömedicin och yrkesmedicin; organochlorine pesticides; persistent organic pollutants; Pharmacology and Toxicology; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Public; Toxicology
• ISSN: 0091-6765; 1552-9924
• DOI: 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. Citation: 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.