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ARS Home » Plains Area » Fargo, North Dakota » Edward T. Schafer Agricultural Research Center » Animal Metabolism-Agricultural Chemicals Research » Research » Publications at this Location » Publication #235892
Title: Hypertension, Cardiac Hypertrophy, and Impaired Vascular Relaxation Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin are Associated with Increased Superoxide

Author
item KOPF, PHILLIP - UNIV OF NEW MEXICO
item Huwe, Janice
item WALKER, MARY - UNIV OF NEW MEXICO

Submitted to: Cardiovascular Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/1/2008
Publication Date: 10/11/2008
Citation: Kopf, P.G., Huwe, J.K., Walker, M.K. 2008. Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide. Cardiovascular Toxicology 8:181-193.

Interpretive Summary: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant known to cause numerous health effects in animals. In this study, mice were used as a model to demonstrate the effect that continuous exposure to TCDD has on the heart and blood pressure. Adult mice were dosed three times a week with low amounts of TCDD and their blood pressure, heart rate, and other cardiovascular characteristics were monitored. During the course of the study, mice exposed to TCDD experienced several high blood pressure episodes compared to control mice. Other markers for heart disease were also observed in the TCDD-exposed mice including an increase in the size of certain heart compartments and vascular dysfunction. The results of this study suggest that repeated or continuous exposure to TCDD can lead to hypertension and cardiovascular disease.

Technical Abstract: The mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the incidence of human cardiovascular disease are not known. We investigated the degree to which cardiovascular disease develops in mice following subchronic TCDD exposure. Adult male C57BL/6 mice were dosed with vehicle or 300 ng TCDD/kg by oral gavage three times per week for 60 days. Blood pressure was recorded by radiotelemetry and aortic endothelial function was assessed by acetylcholine-induced vasorelaxation. Mean arterial pressure of TCDD-exposed mice was increased significantly by day 4 and between days 7–10, 25–35, and 45–60 with two periods of normalization on days 11–24 and days 36–39. Consistent with a prolonged period of systemic hypertension, heart weight was increased and was associated with concentric left ventricular hypertrophy. Significant increases in superoxide production also were observed in the kidney, heart, and aorta of TCDD-exposed mice. Furthermore, increased aortic superoxide resulted in endothelial dysfunction as demonstrated by significant impairment of acetylcholine-induced vasorelaxation in TCDD-exposed mice, which was restored by tempol, a superoxide dismutase (SOD) mimetic. Our model is the first to definitely demonstrate that sustained AhR activation by TCDD increases blood pressure and induces cardiac hypertrophy, which may be mediated, in part, by increased superoxide.