Renal epoxyeicosatrienoic acid synthesis during pregnancy.
Renal epoxyeicosatrienoic acid synthesis during pregnancy.
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DOI：
10.1152/ajprenal.00170.2004
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Yiqiang Zhou;Hsin-Hsin Chang-Hsin;Juan Du;Cong-Yi Wang;Z. Dong;M. Wang
中科院分区：
文献类型：
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作者：
Yiqiang Zhou;Hsin-Hsin Chang-Hsin;Juan Du;Cong-Yi Wang;Z. Dong;M. Wang
环氧二十碳三烯酸 (EET) 属于细胞色素 P-450 (CYP) 衍生的类二十烷酸，在多种动物模型中与舒张肾小动脉、抑制肾单位钠转运和调节血压有关。由于妊娠与血压变化相关，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 天、第 12 天和第 19 天肾微粒体环氧化酶活性分别增加 47%、97% 和 63%。妊娠期间环氧化酶活性的升高与妊娠第 6、12 和 19 天 CYP2C11、CYP2C23 和 CYP2J2 蛋白表达的增加相关。此外，免疫组织化学分析显示，妊娠第6、12和19天妊娠大鼠肾小管CYP2C11、CYP2C23和CYP2J2表达显着增加。给予雌性大鼠中选择性环氧合酶抑制剂 6-(2-炔丙基氧基苯基)己酸 (PPOH)，可对微粒体环氧合酶活性产生剂量依赖性抑制，但对 omega-羟化酶活性没有显着影响。有趣的是，施用 PPOH（从怀孕第 15 天开始，持续 4 天，20 mg.kg(-1).day(-1)）可使血压增加 21 mmHg，并导致胎仔体重显着下降（对照为 1.3 +/- 0.08 g，PPOH 为 1.1 +/- 0.06 g）。此外，PPOH治疗显着降低妊娠大鼠肾微粒体环氧化酶活性以及CYP2C11、CYP2C23和CYP2J的表达。这项研究表明，妊娠期间肾脏中的 EET 合成升高，CYP2C11、2C23 和 CYP2J2 是肾脏 EET 合成变化的原因。抑制结果表明PPOH下调肾环氧化酶活性导致妊娠大鼠高血压。这项研究表明 EET 可能有助于控制怀孕期间的血压。
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.