Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats
Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt hypertensive rats
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DOI：
10.1016/j.vph.2015.08.013
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发表时间：
2015-10-01
影响因子：
4
通讯作者：
Cervenka, Ludek
中科院分区：
文献类型：
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作者：
Alanova, Petra;Huskova, Zuzana;Cervenka, Ludek
本研究观察了新型口服活性14，15-环氧二十碳三烯酸类似物（EET-A）对两肾一夹（2K 1C）Goldblatt高血压大鼠高血压持续期血压（BP）和心肌梗死面积（IS）的影响。在放置夹子后的第31天和第35天之间，用EET-A治疗大鼠，并通过无线电遥测监测血压;假手术血压正常的大鼠用作对照。环氧二十碳三烯酸的组织浓度作为环氧合酶代谢产物产生的标志。造成大鼠急性心肌缺血/再灌注（I/R）损伤，测定IS。我们发现EET-A治疗没有降低2K 1C大鼠的血压，也没有改变2K 1C或假手术大鼠中生物活性环氧酶代谢产物的可用性。与正常血压对照组相比，未治疗的2K 1C大鼠的心肌IS显著较小，EET-A降低了对照组的心肌IS，但在2K 1C大鼠中没有。我们的研究结果表明，在持续性高血压阶段，2K 1C Goldblatt高血压大鼠表现出增加心脏耐受性I/R损伤相比，血压正常的控制，并在这个人类肾血管性高血压的动物模型短期治疗EET-A不诱导任何抗高血压和心脏保护作用。(C)2015 Elsevier Inc. All rights reserved.
This study examined the effects of a novel orally active 14,15-epoxyeicosatrienoic acid analog (EET-A) on blood pressure (BP) and myocardial infarct size (IS) in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats during sustained phase of hypertension. Between days 31 and 35 after clip placement the rats were treated with EET-A and BP was monitored by radiotelemetry; sham-operated normotensive rats were used as controls. Tissue concentrations of epoxyeicosatrienoic acids served as a marker of production of epoxygenase metabolites. The rats were subjected to acute myocardial ischemia/reperfusion (I/R) injury and IS was determined. We found that EET-A treatment did not lower BP in 2K1C rats and did not alter availability of biologically active epoxygenase metabolites in 2K1C or in sham-operated rats. The myocardial IS was significantly smaller in untreated 2K1C rats as compared with normotensive controls and EET-A reduced it in controls but not in 2K1C rats. Our findings suggest that during the phase of sustained hypertension 2K1C Goldblatt hypertensive rats exhibit increased cardiac tolerance to I/R injury as compared with normotensive controls, and that in this animal model of human renovascular hypertension short-term treatment with EET-A does not induce any antihypertensive and cardioprotective actions. (C) 2015 Elsevier Inc. All rights reserved.