Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension.
Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension.
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DOI：
10.1155/2011/502631
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
El-Marakby A
中科院分区：
文献类型：
--
作者：
Lee DL;Wilson JL;Duan R;Hudson T;El-Marakby A
非诺贝特激活过氧化物酶体增殖物激活受体-α（PPAR-α）可降低DOCA-盐高血压期间的血压和钠潴留。过氧化物酶体增殖物激活受体-α激活减少炎性细胞因子的表达，如白细胞介素-6（IL-6）。非诺贝特还诱导细胞色素P450 4A（CYP 4A）并增加20-羟基二十碳四烯酸（20-HETE）的产生。本研究测试了在DOCA盐高血压7天期间，非诺贝特给药是否会通过减弱血浆IL-6和肾脏环氧合酶-2（考克斯-2）的表达，同时增加肾脏CYP 4A的表达来降低血压。我们对12-14周龄的雄性Swiss韦伯斯特小鼠进行单肾切除术，并在对照、DOCA-盐（1.5 mg/g）处理的小鼠中植入生物遥测装置，所述DOCA-盐处理的小鼠具有或不具有非诺贝特（500 mg/kg/天，在玉米油中，胃内）。非诺贝特显著降低平均动脉压和血浆IL-6。在肾匀浆中，非诺贝特增加CYP 4A和降低考克斯-2表达。各组间肾脏细胞色素P450、家族2、亚家族c、多肽23（CYP 2C 23）和可溶性谷胱甘肽水解酶（sEH）表达无差异。我们的研究结果表明，在DOCA-盐高血压过程中，非诺贝特激活PPAR-α的降压作用涉及血浆IL-6和考克斯-2的减少，同时增加CYP 4A的表达。我们的研究结果也可能表明，过氧化物酶体增殖物激活物-α通过减少考克斯-2表达保护肾脏免受肾损伤。
Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.
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影响因子：
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