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首页> 外文期刊>American Journal of Physiology >Renal epoxyeicosatrienoic acid synthesis during pregnancy.
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Renal epoxyeicosatrienoic acid synthesis during pregnancy.

机译：妊娠期间肾环氧二十碳三烯酸的合成。

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Epoxyeicosatrienoic acids (EETs), which belong to cytochrome P-450 (CYP)-derived eicosanoids, have been implicated to vasodilate renal arterioles, inhibit sodium transport in the nephron, and regulate blood pressure in several animal models. Because pregnancy is associated with changes of blood pressure, the aim of this study was to examine whether renal EET synthesis is altered and whether EETs are involved in blood pressure regulation during pregnancy in rats. Renal microsomal epoxygenase activity increased by 47, 97, and 63% on days 6, 12, and 19 of gestation, respectively. The elevation of epoxygenase activity during pregnancy was associated with an increase in CYP2C11, CYP2C23, and CYP2J2 protein expression on days 6, 12, and 19 of gestation. Moreover, immunohistochemical analysis showed that renal tubular CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in pregnant rats on days 6, 12, and 19 of gestation. Administration of 6-(2-propargyloxyphenyl)hexanoic acid (PPOH), a selective epoxygenase inhibitor, caused a dose-dependent inhibition of microsomal expoxygenase activity without a significant effect on omega-hydroxylase activity in female rats. Interestingly, administration of PPOH (20 mg.kg(-1).day(-1) for 4 days starting on day 15 of pregnancy) increased blood pressure by 21 mmHg and caused a significant decrease in the body weight of fetal pups (1.3 +/- 0.08 g in control vs. 1.1 +/- 0.06 g in PPOH). Moreover, PPOH treatment significantly decreased renal microsomal epoxygenase activity and the expression of CYP2C11, CYP2C23, and CYP2J in pregnant rats. This study demonstrates that EET synthesis in the kidney is elevated during pregnancy, and CYP2C11, 2C23, and CYP2J2 are responsible for the change of renal EET synthesis. The inhibition results demonstrate that the downregulation of renal epoxygenase activity by PPOH causes hypertension in pregnant rats. This study suggests that EETs may contribute to the control of blood pressure during pregnancy.
机译：环氧二十碳三烯酸（EETs），属于细胞色素P-450（CYP）衍生的类二十烷酸，在几种动物模型中均被认为可以使肾小动脉血管舒张，抑制钠转运，并调节血压。因为妊娠与血压的变化有关，所以本研究的目的是检查大鼠妊娠期间肾脏EET合成是否发生改变以及EET是否参与血压调节。妊娠第6、12和19天，肾脏微粒体环氧合酶活性分别增加了47％，97％和63％。妊娠期间环氧合酶活性的升高与妊娠第6、12和19天CYP2C11，CYP2C23和CYP2J2蛋白表达的增加有关。此外，免疫组织化学分析显示，妊娠第6、12和19天，妊娠大鼠的肾小管CYP2C11，CYP2C23和CYP2J2表达显着增加。选择性环氧合酶抑制剂6-（2-炔丙基氧基苯基）己酸（PPOH）的使用导致剂量依赖性抑制微粒体环氧合酶活性，而对雌性大鼠的ω-羟化酶活性无明显影响。有趣的是，从怀孕第15天开始服用PPOH（20 mg.kg（-1）.day（-1）4天）可使血压升高21 mmHg，并导致幼崽的体重显着降低（1.3对照组为+/- 0.08克，而PPOH为1.1 +/- 0.06克。此外，PPOH处理可显着降低妊娠大鼠的肾微粒体环氧合酶活性以及CYP2C11，CYP2C23和CYP2J的表达。这项研究表明，怀孕期间肾脏中EET的合成会升高，并且CYP2C11、2C23和CYP2J2负责肾脏EET合成的变化。抑制结果表明，PPOH对肾环氧合酶活性的下调会引起妊娠大鼠高血压。这项研究表明，EETs可能有助于控制怀孕期间的血压。

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