Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide.
Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide.
复制标题
高血压，心脏肥大和受损的血管弛豫受到2,3,7,8-四氯迪本佐-P-二恶英的诱导，与超氧化物的增加有关。
DOI：
10.1007/s12012-008-9027-x
复制
发表时间：
2008-12
影响因子：
3.2
通讯作者：
Walker, Mary K.
中科院分区：
文献类型：
--
作者：
Kopf, Phillip G.;Huwe, Janice K.;Walker, Mary K.
2，3，7，8-四氯二苯并对二恶英（TCDD）增加人类心血管疾病发病率的机制尚不清楚。我们研究了亚慢性TCDD暴露后小鼠心血管疾病的发展程度。成年雄性C57 BL/6小鼠经口灌胃给予溶剂或300 ng TCDD/kg，每周三次，持续60天。通过无线电遥测记录血压，通过乙酰胆碱诱导的血管舒张评估主动脉内皮功能。暴露于TCDD的小鼠的平均动脉压在第4天以及第7-10天、第25-35天和第45-60天之间显著增加，在第11-24天和第36-39天有两个正常化时期。与长期的全身性高血压一致，心脏重量增加，并与向心性左心室肥大相关。在接触TCDD的小鼠的肾脏、心脏和主动脉中也观察到超氧化物产生的显著增加。此外，增加主动脉超氧化物导致内皮功能障碍，表现为显着损害乙酰胆碱诱导的血管舒张TCDD暴露的小鼠，这是恢复tempol，超氧化物歧化酶（SOD）模拟。我们的模型是第一个明确证明，持续的AhR激活TCDD增加血压，并诱导心肌肥大，这可能是介导的，在一定程度上，通过增加超氧化物。
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.
登录
查看更多内容
影响因子：
3.8
作者：
Dong, W;Teraoka, H;Hiraga, T
通讯作者：
Hiraga, T
DOI：
10.1111/j.1742-7843.2004.950305.x
发表时间：
2004-09-01
影响因子：
3.1
作者：
Alsharif, NZ;Hassoun, EA
通讯作者：
Hassoun, EA
影响因子：
4.5
作者：
Brunnberg, Sara;Andersson, Patrik;Hanberg, Annika
通讯作者：
Hanberg, Annika
影响因子：
15.9
作者：
Landmesser, U;Dikalov, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
6.1
作者：
Huwe, JK;Smith, DJ
通讯作者：
Smith, DJ