Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion
Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion
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DOI：
10.1161/01.hyp.0000113294.06704.64
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发表时间：
2004-02-01
期刊：
影响因子：
8.3
通讯作者：
Nithipatikom, K
中科院分区：
文献类型：
--
作者：
Goodfriend, TL;Ball, DL;Nithipatikom, K
血浆醛固酮水平并不总是由肾素活性和钾浓度来预测的。其中原因不明的是一些肥胖者体内醛固酮水平升高。肥胖的特点是血浆脂肪酸和氧化应激增加。我们假设氧化脂肪酸刺激醛固酮生成。最容易被氧化的脂肪酸是多不饱和脂肪酸，其中最丰富的是亚油酸。我们测试了氧化亚油酸衍生物对大鼠肾上腺细胞的影响。其中一种衍生物12,13-环氧-9-酮-10（反式）-十八烯酸（EKODE）特别有效。EKODE在0.5 ~ 5 μ mol/L浓度范围内刺激醛固酮生成，在高剂量范围内抑制醛固酮生成。EKODE的刺激作用在血管紧张素和钾的作用次极大时最为突出。脂质作用机制为孕烯醇酮的早期通路；心房利钠肽可抑制其作用。采用液相色谱/质谱法测定血浆EKODE。所有测试的人血浆中都含有EKODE，浓度范围为10（-9）至5 × 10(-7) mol/L。在24名成人样本中，EKODE水平与醛固酮直接相关（r=0.53， P=0.007）。在该队列中的12名黑人中，EKODE还与体重指数和收缩压相关。这些其他相关性在白人受试者中没有发现。结果表明，除花生四烯外，多不饱和脂肪酸的氧化衍生物具有生物活性。从亚油酸中提取的EKODE等化合物可能会影响人体肾上腺类固醇的产生，并介导肥胖和氧化应激的一些有害影响，尤其是在黑人中。
Plasma levels of aldosterone are not always predictable from the activity of renin and the concentration of potassium. Among the unexplained are elevated levels of aldosterone in some obese humans. Obesity is characterized by increased plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids stimulate aldosteronogenesis. The most readily oxidized fatty acids are the polyunsaturated, and the most abundant of those is linoleic acid. We tested oxidized derivatives of linoleic acid for effects on rat adrenal cells. One derivative, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), was particularly potent. EKODE stimulated aldosteronogenesis at concentrations from 0.5 to 5 mumol/L, and inhibited aldosteronogenesis at higher doses. EKODE's stimulatory effect was most prominent when angiotensin and potassium effects were submaximal. The lipid's mechanism of action was on the early pathway leading to pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas tested contained EKODE in concentrations ranging from 10(-9) to 5x10(-7) mol/L. In samples from 24 adults, levels of EKODE correlated directly with aldosterone (r=0.53, P=0.007). In the 12 blacks in that cohort, EKODE also correlated with body mass index and systolic pressure. Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks.