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首页> 外文期刊>American Journal of Physiology >Cytochrome P-450-derived eicosanoids participate in the renal functional effects of ET-1 in the anesthetized rat.
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Cytochrome P-450-derived eicosanoids participate in the renal functional effects of ET-1 in the anesthetized rat.

机译：细胞色素P-450衍生的类花生酸参与麻醉大鼠ET-1的肾功能作用。

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摘要

We evaluated the contribution of cytochrome P-450 (CYP450)-dependent arachidonic acid (AA) metabolites and prostanoids to the renal hemodynamic and tubular effects of endothelin-1 (ET-1) in anesthetized rats. Either ET-1 (0.3, 1.0, and 3 pmol.kg-1.min-1) or vehicle was infused intravenously during two to three 30-min clearance experimental periods. Only high-dose ET-1 increased mean arterial pressure: control, 75 +/- 3 mmHg vs. experimental, 84 +/- 4 mmHg. A dose-dependent diuretic-natriuretic response to ET-1 occurred despite progressive declines in glomerular filtration rate (GFR) and renal blood flow. In the face of a 36% reduction in GFR in response to the highest dose of ET-1, urinary sodium excretion (UNaV) increased threefold from 0.57 +/- 0.11 to 1.6 +/- 0.10 mumol.100 g-1.min-1. Indomethacin (5 mg/kg) decreased basal GFR from 1.2 +/- 0.3 ml.100 g-1.min-1 to 0.8 +/- 0.1 ml.100 g-1.min-1 and potentiated the GFR lowering action of ET-1 associated with reductions in UNaV and urine volume. Cobalt chloride (CoCl2) and dibromododec-11-enoic acid (DBDD), which diminish CYP450-dependent AA metabolism through different mechanisms, were used to identify CYP450 products mediating the renal functional actions of ET-1. DBDD (12.5 micrograms/min) reduced urinary excretion of 20-hydroxyeicosatetraenoic acid from 3.4 +/- 0.9 (control) to 1.1 +/- 0.6 ng/h and abolished the negative effects of ET-1 on GFR while decreasing the diuretic-natriuretic action of ET-1. Similar effects were produced by CoCl2. Clotrimazole, an inhibitor of epoxygenase activity, was without effect on ET-1-induced renal functional changes. Thus the capacity of ET-1 to enhance prostaglandin production was primarily expressed in terms of positive effects on renal hemodynamics. In contrast, CYP450 products promoted sodium excretion despite negative effects on renal hemodynamics.
机译：我们评估了细胞色素P-450（CYP450）依赖性花生四烯酸（AA）代谢产物和前列腺素对麻醉大鼠中肾素1（ET-1）的肾血流动力学和肾小管作用的贡献。在两到三个30分钟的清除实验期间，静脉内注入ET-1（0.3、1.0和3 pmol.kg-1.min-1）或载体。只有大剂量的ET-1会增加平均动脉压：对照组为75 +/- 3 mmHg，而实验组为84 +/- 4 mmHg。尽管肾小球滤过率（GFR）和肾血流量逐渐下降，但对ET-1仍存在剂量依赖性利尿钠尿反应。面对最高剂量的ET-1，GFR降低了36％，尿钠排泄量（UNaV）从0.57 +/- 0.11摩尔增加了1.6倍至0.1 +/- 0.10摩尔。100g-1.min- 1。消炎痛（5 mg / kg）将基础GFR从1.2 +/- 0.3 ml.100 g-1.min-1降至0.8 +/- 0.1 ml.100 g-1.min-1并增强了ET的GFR降低作用-1与UNaV和尿液量减少有关。氯化钴（CoCl2）和二溴十二烷基十一烯酸（DBDD）通过不同的机制减少了CYP450依赖的AA代谢，用于鉴定CYP450产物介导ET-1的肾功能。 DBDD（12.5微克/分钟）可将20-羟基二十碳四烯酸的尿排泄从3.4 +/- 0.9（对照）降低至1.1 +/- 0.6 ng / h，并消除了ET-1对GFR的负面影响，同时减少了利尿钠ET-1的作用。 CoCl2产生了类似的效果。克霉唑是环氧合酶活性的抑制剂，对ET-1诱导的肾功能变化没有影响。因此，ET-1增强前列腺素产生的能力主要表现为对肾脏血液动力学的积极影响。相反，尽管CYP450产品对肾脏血流动力学有负面影响，但仍促进钠排泄。

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