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首页> 外文期刊>Journal of hypertension >Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats.
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Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats.

机译：花生四烯酸的肾内细胞色素P-450代谢产物在调节两肾一夹式Goldblatt高血压大鼠的非闭合性肾功能中的作用。

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OBJECTIVE: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. METHODS: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, omega-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. RESULTS: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. CONCLUSION: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.
机译：目的：环氧二十碳三烯酸（EETs）和20-羟基二十碳四烯酸（20-HETE）作为花生四烯酸的细胞色素P-450代谢产物，在调节二肾一夹（2K1C）高血压的非肾脏功能中的作用在最初和稳定的高血压阶段，即分别在截断后7或27天，对大鼠进行了研究。方法：雄性汉诺威Sprague-Dawley大鼠的右肾动脉被夹住或进行了假手术。测量了EET，其非活性代谢物二羟基二十碳三烯酸和20-HETE的尿排泄量。还测定了肾内细胞色素P-450蛋白的表达以及环氧合酶，ω-羟化酶和可溶性环氧化物水解酶的活性。测量了肾脏不流动的肾脏的血液动力学和电解质排泄对左EETs抑制剂或20-HETE形成抑制剂（分别为MS-PPOH和DDMS）的左肾动脉输注的响应。结果：仅在剪毛后第27天，在2K1C大鼠中，EET的尿排泄明显低于假手术动物，而20-HETE的尿排泄却较高。肾内抑制EET可以显着降低假手术组的肾脏血液动力学和钠排泄，但在2K1C大鼠中则没有。肾内抑制20-HETE可以降低假手术大鼠的钠排泄，但会引起2K1C大鼠肾血流动力学和钠排泄增加。结论：我们的结果表明，与假手术动物的肾脏相比，Goldblatt 2K1C大鼠在持续性高血压阶段的非闭合肾脏表现出降低的肾内EET和升高的20-HETE水平。这表明在此稳定阶段中细胞色素P-450衍生代谢产物的产生和作用的改变有助于Goldblatt 2K1C高血压的机制。

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