Gender differences of renal CYP-derived eicosanoid synthesis in rats fed a high-fat diet.
Gender differences of renal CYP-derived eicosanoid synthesis in rats fed a high-fat diet.
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DOI：
10.1016/j.amjhyper.2004.10.033
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发表时间：
2005-04
影响因子：
3.2
通讯作者：
Yiqiang Zhou;Songbai Lin;Hsin-Hsin Chang-Hsin;Juan Du;Z. Dong;A. Dorrance;M. Brands;M. Wang
中科院分区：
文献类型：
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作者：
Yiqiang Zhou;Songbai Lin;Hsin-Hsin Chang-Hsin;Juan Du;Z. Dong;A. Dorrance;M. Brands;M. Wang
肾细胞色素P450 （CYP）衍生的类二十烷酸、羟基二十烷四烯酸（HETEs）、环氧二十烷三烯酸（EETs）和二羟基二十烷三烯酸（DHETs）已被证明会影响肾功能和血压（BP）。我们最近报道了高脂肪饮食治疗雄性大鼠的血压升高，并减少肾脏中这些类二十烷醇的产生。然而，雌性大鼠肾类二十烷酸合成的下调发生在什么水平，以及HF饮食对雌性大鼠肾类二十烷酸合成的调节是否有影响，目前尚不清楚。本研究的目的是确定HF雄性和雌性大鼠肾中cyp衍生的类二十烷酸合成及其与血压调节的关系。方法在第一组实验中，雄性和雌性大鼠分别饲喂HF和对照饲料10周。在第二组实验中，雄性和雌性大鼠分别饲喂HF饲粮10 d。在第三组实验中，以hf喂养的雌性大鼠和对照大鼠分别给予5α-二氢睾酮治疗4周。治疗后测定血压、尿钠、钠平衡、类二十烷生成和CYP酶表达。结果HF雄性大鼠血压升高，肾皮质类二十烷酸分泌减少，而HF雌性大鼠血压和类二十烷酸分泌未见变化。HF处理还导致HF雄性大鼠近端小管类二十烷酸产生明显减少，CYP4A和2C23表达明显降低。此外，HF饮食处理引起雄性大鼠的累积钠平衡增加和血压升高，而雌性大鼠的累积钠平衡和血压没有变化。5α-二氢睾酮处理可增加雌性大鼠的血压和肾微血管中20-HETE的产生，但对对照组和hf喂养的雌性大鼠的尿钠排泄和肾微血管EET的产生没有影响。结论HF治疗对肾类二十烷酸合成、钠平衡和血压的调节存在性别差异，雄激素可能在HF和对照组雌性大鼠肾微血管20-HETE生成上调中起一定作用。Am J Hypertens 2005；18:53 - 537©2005美国高血压杂志
BackgroundRenal cytochrome P450 (CYP)-derived eicosanoids, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs), have been shown to affect renal function and blood pressure (BP). We recently reported that high fat (HF) diet treatment in male rats increases BP and decreases production of these eicosanoids in the kidneys. However, at what level the downregulation of renal eicosanoid synthesis occurs and whether the HF diet has any effects on the regulation of renal eicosanoid synthesis in female rats are not known. The purpose of this study was to determine renal CYP-derived eicosanoid synthesis and its association with BP regulation in HF male and female rats.MethodsIn the first set of experiments, male and female rats were fed the HF or control diet for 10 weeks. In the second set of experiments, male and female rats were fed the HF diet for 10 days. In the third set of experiments, HF-fed and control female rats were treated with 5α-dihydrotestosterone for 4 weeks. After treatment, BP, urinary sodium, sodium balance, eicosanoid production, and CYP enzyme expression were determined.ResultsAn elevation of BP and a decrease of renal cortical eicosanoid production were found in HF male rats, but no BP and eicosanoid production changes were observed in HF female rats. The HF treatment also caused a significant decrease of eicosanoid production and a decrease of CYP4A and 2C23 expression in the proximal tubules of HF male rats. Moreover, the HF diet treatment in male rats caused an increase in cumulative sodium balance and an elevation of BP, whereas no change in cumulative sodium balance and BP was observed in female rats. The treatment of 5α-dihydrotestosterone increased BP and 20-HETE production in the renal microvessels, but had no effect on urinary sodium excretion and renal microvessel EET production in both control and HF-fed female rats.ConclusionsThese results demonstrate that there are gender-specific differences in regulation of renal eicosanoid synthesis, sodium balance, and BP caused by HF treatment, and it appears that androgens play some role in upregulation of renal microvessel 20-HETE production in both HF and control female rats. Am J Hypertens 2005;18:530–537 © 2005 American Journal of Hypertension, Ltd.