Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus
Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus
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DOI：
10.1152/ajprenal.00188.2005
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Roman, RJ
中科院分区：
文献类型：
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作者：
Sarkis, A;Ito, O;Roman, RJ
尿崩症大鼠肾脏细胞色素P-450依赖的花生四烯酸代谢。AM J Physiol Renal Physiol 289：F1333-F1340,2005.2005年7月12日首次发表；DOI：10.1152/ajprenal.00188.2005。-这项研究比较了Brattleboro(BB)(加压素缺乏)和Long-Evans(Long-Evans)对照组大鼠花生四烯酸的肾脏代谢，以及细胞色素P-450(CYP)抑制剂1-氨基苯并三氮唑(ABT)对这些动物肾功能的影响。BB大鼠肾皮质和外髓微粒体产生的20-羟基二十碳四烯酸(20-HETE)显著高于LE大鼠(155+/-16vs.92+/-13和59+/-7vs.33+/-3pmol中心点min中心点1中心点镁蛋白(-1))。肾皮质环氧合酶活性在这些菌株中没有差异。肾皮质和外髓细胞色素P4A蛋白在肾皮质和外髓中的表达分别比正常对照组高58%和78%。用血管加压素2型受体激动剂慢性处理BB大鼠1wk后，肾脏20-HETE的产生正常化。ABT长期阻断20-HETE和EETs的形成对LE大鼠肾功能无明显影响。而经ABT治疗的BB大鼠尿流量增加54%，尿渗透压下降33%。血浆催产素水平从7.2+/-1.3降至3.9+/-1.0pg/ml，ABT对BB大鼠的作用可通过长期输注催产素(0.7 ng中心点分钟(-1)中心点100g(-1))来维持较高的血浆催产素水平而减弱。这些结果表明，由于缺乏加压素，BB大鼠肾脏中20-HETE和20-HETE的形成和细胞色素P4A蛋白的表达增加，ABT慢性阻断20-HETE和EETS的形成，可能通过降低催产素的循环水平来促进加压素缺乏的BB大鼠的水排泄。
Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus. Am J Physiol Renal Physiol 289: F1333-F1340, 2005. First published July 12, 2005; doi:10.1152/ajprenal.00188.2005.-This study compared the renal metabolism of arachidonic acid in Brattleboro (BB) ( vasopressin deficient) and Long-Evans (LE) control rats and the effects of a cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) on renal function in these animals. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical and outer medullary microsomes was significantly greater in BB than in LE rats (155 +/- 16 vs. 92 +/- 13 and 59 +/- 7 vs. 33 +/- 3 pmol center dot min center dot 1 center dot mg protein(-1)). Renal cortical epoxygenase activity was not different in these strains. The expression of CYP4A proteins was 58 and 78% higher in the renal cortex and outer medulla of BB than in LE rats. Chronic treatment of BB rats with a vasopressin type 2 receptor agonist for 1 wk normalized the renal production of 20-HETE. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effect on renal function in LE rats. However, urine flow increased by 54% and urine osmolarity decreased by 33% in BB rats treated with ABT. Plasma levels of oxytocin fell significantly from 7.2 +/- 1.3 to 3.9 +/- 1.0 pg/ml. The effects of ABT in BB rats were attenuated by chronic infusion of oxytocin (0.7 ng center dot min(-1) center dot 100 g(-1)) to maintain fixed high plasma levels of this hormone. These results indicate that the expression of CYP4A protein and the renal formation of 20-HETE are elevated in the kidney of BB rats due to a lack of vasopressin and that chronic blockade of the formation of 20-HETE and EETs with ABT promotes water excretion in vasopressin-deficient BB rats by reducing the circulating levels of oxytocin, which is a weak vasopressin agonist.