Fenofibrate prevents the development of angiotensin II-dependent hypertension in mice
Fenofibrate prevents the development of angiotensin II-dependent hypertension in mice
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DOI：
10.1161/01.hyp.0000153317.06072.2e
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发表时间：
2005-04-01
期刊：
影响因子：
8.3
通讯作者：
Stec, DE
中科院分区：
文献类型：
--
作者：
Vera, T;Taylor, M;Stec, DE
先前的研究表明，C57/B6小鼠和大鼠的肝脏中20-羟基廿三碳烯酸（20-HETE）的产生相似，但该品系小鼠的肾脏中20-HETE的产生非常低。本研究探讨了非诺贝特（FF）诱导肾脏产生20-HETE对C57 BL/6 J小鼠血管紧张素II（Ang II）依赖性高血压的影响。将小鼠分成4组，并用媒介物（对照）、FF（90 mg/kg/天，IP）、Ang II（1000 ng/kg/分钟，SC）和Ang II加FF处理。对照组和FF治疗组小鼠（n=7）的平均动脉血压（MAP）平均为109 +/- 4和106 +/- 2 mm Hg。血管紧张素II治疗的小鼠MAP显著增加至144 +/- 4 mmHg（n=7）。然而，FF治疗阻止了Ang II依赖性高血压的发展，在用Ang II加FF治疗的小鼠中MAP平均为115 +/-5 mm Hg（n=7）。在对照组（n=7）和Ang II治疗组（n=7）小鼠中，20-HETE的肾产生非常低，而在FF治疗组（n=7）和Ang II加FF治疗组（n=7）小鼠中，20-HETE的肾产生增加>2倍。在用FF和Ang II加FF处理的小鼠的肾脏中Cyp 4A蛋白的水平显著增加，但在肾血管系统中没有。这些结果表明，20-HETE在肾小管中的产生的上调可能有助于FF治疗在C57 BL/6 J小鼠中的Ang II依赖性高血压中的降压作用。
Previous studies have indicated that the production of 20-hydroxyecisatatraenoic acid (20-HETE) is similar in the liver of C57/B6 mice and rats, but the renal production of 20-HETE is very low in this strain of mice. The present study examined the effects of induction of the renal production of 20-HETE with fenofibrate (FF) on the development of angiotensin II (Ang II)-dependent hypertension in C57BL/6J mice. The mice were divided into 4 groups and treated with vehicle (control), FF (90 mg/kg per day, IP), Ang II (1000 ng/kg per minute, SC), and Ang II plus FF. Mean arterial blood pressure (MAP) averaged 109 +/- 4 and 106 +/- 2 mm Hg in control and FF-treated mice (n=7). MAP was significantly increased in the Ang II-treated mice to 144 +/- 4 mmHg (n=7). However, FF treatment prevented the development of Ang II-dependent hypertension, with MAP averaging 115 +/- 5 mm Hg in mice treated with both Ang II plus FF (n=7). Renal production of 20-HETE was very low in control (n=7) and Ang II-treated (n=7) mice and was increased by >2-fold in FF-treated (n=7) and Ang II plus FF-treated (n=7) mice. The levels of Cyp4A proteins were markedly increased in the kidneys of mice treated with FF and Ang II plus FF but not in the renal vasculature. These results suggest that upregulation of the production of 20-HETE in renal tubules may contribute to the blood pressure-lowering effects of FF treatment in Ang II-dependent hypertension in C57BL/6J mice.