Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats
Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats
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DOI：
10.1152/ajpheart.01267.2010
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发表时间：
2011-06-01
影响因子：
4.8
通讯作者：
Carroll, Mairead A.
中科院分区：
文献类型：
--
作者：
Jiang, Houli;Quilley, John;Carroll, Mairead A.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容自发性高血压大鼠血浆反式-EETs升高和血压降低。Am J Physiol心圈Physiol 300：H1990-H1996,2011。2011年3月11日首次出版；DOI：10.1152/ajpheart.01267.2010.-Epoxyeicosatrienoic酸(EETs)是血管扩张剂、利钠药和抗炎脂质调节剂。顺式和反式EET都储存在循环中的磷脂和红细胞(RBC)中；可溶性环氧化物水解酶(SEH)对反式EET的最大水解速度(V(Max))是顺式EET的三倍。由于自发性高血压大鼠(SHR)的红细胞表现出sEH活性升高，推测SHR中反式EETs的缺乏会导致血压(BP)升高。由于顺式-4-[4-(3-金刚烷-1-酰脲)环己氧基]苯甲酸(AUCB；2 mg·kg(-1).day(-1)，连续7天)抑制SHR的sEH，使SHR的平均血压从176+/-8降至153+/-5毫米汞柱(P<；0.05)，而对照Wistar-京都大鼠(WKY)的血压未受影响。SHR组血浆EETs水平低于年龄匹配的对照组WKY组(16.4+/-1.6vs.26.1+/-1.8 ng/ml，P<0.05)。AUCB治疗的SHR血压下降与血浆EETs升高有关，这主要是通过将反式EET从4.1+/-0.2 ng/ml增加到7.9+/-1.5 ng/ml(P<；0.05)。与自发性高血压大鼠血浆反式EET升高和血压下降的作用一致，14，15-反式EET对大鼠弓状预缩血管的松弛作用(ED(50)10(-10)M；最大扩张59+/-15微米)强于顺式异构体(ED(50)10(-9)M；最大扩张30+/-11微米)。11，12-EET的顺式和反式异构体与8，9-EET的异构体是相同的扩张剂。总之，抑制sEH导致自发性高血压大鼠血浆反式-EETs增加两倍，平均血压降低。反式与非反式的血管扩张剂效力更大。顺式EET可能与sEH抑制剂的降压作用有关。
Jiang H, Quilley J, Doumad AB, Zhu AG, Falck JR, Hammock BD, Stier CT, Jr, Carroll MA. Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 300: H1990-H1996, 2011. First published March 11, 2011; doi: 10.1152/ajpheart.01267.2010.-Epoxyeicosatrienoic acids (EETs) are vasodilator, natriuretic, and antiinflammatory lipid mediators. Both cis- and trans-EETs are stored in phospholipids and in red blood cells (RBCs) in the circulation; the maximal velocity (V(max)) of trans-EET hydrolysis by soluble epoxide hydrolase (sEH) is threefold that of cis-EETs. Because RBCs of the spontaneously hypertensive rat (SHR) exhibit increased sEH activity, a deficiency of trans-EETs in the SHR was hypothesized to increase blood pressure (BP). This prediction was fulfilled, since sEH inhibition with cis-4-[4-(3-adamantan-1-ylureido) cyclohexyloxy] benzoic acid (AUCB; 2 mg.kg(-1).day(-1) for 7 days) in the SHR reduced mean BP from 176 +/- 8 to 153 +/- 5 mmHg (P < 0.05), whereas BP in the control Wistar-Kyoto rat (WKY) was unaffected. Plasma levels of EETs in the SHR were lower than in the age-matched control WKY (16.4 +/- 1.6 vs. 26.1 +/- 1.8 ng/ml; P < 0.05). The decrease in BP in the SHR treated with AUCB was associated with an increase in plasma EETs, which was mostly accounted for by increasing trans-EET from 4.1 +/- 0.2 to 7.9 +/- 1.5 ng/ml (P < 0.05). Consistent with the effect of increased plasma trans-EETs and reduced BP in the SHR, the 14,15-trans-EET was more potent (ED(50) 10(-10) M; maximum dilation 59 +/- 15 mu m) than the cis-isomer (ED(50) 10(-9) M; maximum dilation 30 +/- 11 mu m) in relaxing rat preconstricted arcuate arteries. The 11,12-EET cis- and trans-isomers were equipotent dilators as were the 8,9-EET isomers. In summary, inhibition of sEH resulted in a twofold increase in plasma trans-EETs and reduced mean BP in the SHR. The greater vasodilator potency of trans-vs. cis-EETs may contribute to the antihypertensive effects of sEH inhibitors.