FUNCTION AND REGULATION OF TRANS-EETS

红细胞(RBC)是环氧二十碳三烯酸(EETs)的储存库，它是 由活性氧作用于磷脂中的花生四烯酸形成。一种新的Frans-EET 在红细胞磷脂的锡-2位，形成了最丰富的5，6-反式-EET 超过5，6-c/S-EET，由磷脂酶A2从红细胞中释放出来。ATP，生成单位：mm 红细胞的量，对红细胞EET的释放有双相作用，在低浓度时刺激释放 在高浓度下抑制EET的释放。RBC中的EET估计为 20.2纳克/109个红细胞，相当于每毫升血液中200纳克。血液的其他构成元素 推测携带EET/HETE；我们已经证明，血小板也含有大量的 EET在他们的磷脂中。 5，6-Frans-EET的血管活性高于5，6-c/S-EET 大鼠的叶间动脉和发育区小动脉。此外，5，6-反式-5，6-三聚体的水化产物 EET，二羟基化合物-5，6-红血球蛋白-EET-具有与其母体相同或更强的血管活性 5，6-Frans-EET。在表现出高度氧化应激的实验模型中， 自发性高血压大鼠(SHR)血浆5，6-FRANS-EET水平是正常对照组的两倍 血压正常的WKY大鼠。 我们认为，红细胞是环氧化物的储存库，环氧化物在释放时可能起作用 血管调节能力。3个AIMS将在几个实验中详细探讨这一建议 氧化应激的模型。 目的1：检测肾脏顺式和法式EET的合成和释放，促进其合成和释放的因素 产生及其对肾血管的影响。 目标2：根据顺式和反式-β-内酰胺酶产生的变化来定义对氧化应激的反应 对肾功能至关重要的部位的EETs/DHTs：对于血管系统，肾小球前 微血管(PGMV)；对于小管，为粗大的升支(TAL)。 目标3：确定TRANS-EETs/DHTs与C/S-EETs/DHTs对增强的相对贡献 不同水平自发性高血压大鼠与正常血压大鼠肾血管扩张对AA的反应 肾血流灌注压力。

The red blood cell (RBC) serves as a reservoir of epoxyeicosatrienpic acids (EETs) that are formed by reactive oxygen species acting on arachidonic acid of phospholipids. A novel frans-EET in the Sn-2 position of RBC phospholipids, a 5,6-trans-EET, was formed in greatest abundance exceeding that of 5,6-c/s-EET and released from RBCs by phospholipase A2. ATP, generated in mM quantities by RBCs, has a biphasic action on RBC EET release, stimulating release at low concentrations and inhibiting EET release at high concentrations. EETs in RBCs are estimated to be 20.2 ng/109 RBCs corresponding to 200 ng in 1 ml of blood. Other formed elements of blood presumably carry EETs/HETEs; we have shown that platelets also contain significant quantities of EETs in their phospholipids. The vasoactivity of 5,6-frans-EET is greater than that of 5,6-c/s-EET when tested on renal interlobar arteries and cremasteric arterioles of the rats. Further, the hydration product of 5,6-trans- EET, the dihydroxy compound - 5,6-erythro-EET - has equal or greater vasoactivity than its parent 5,6-frans-EET. In an experimental model exhibiting a high degree of oxidative stress, the spontaneously hypertensive rat (SHR), the levels of 5,6-frans-EET were double those of normotensive WKY rats. We propose that the RBCs serve as a reservoir for epoxides which on release may act in a vasoregulatory capacity. The 3 AIMS will explore this proposal in detail in several experimental models of oxidative stress. AIM 1: Examine renal synthesis and release of cis- and frans-EETs, the factors that promote their production and their effects on renal blood vessels. Aim 2: Define the response to oxidative stress in terms of changes in production of cis- and trans- EETs/DHTs at sites critical to renal function: for the vasculature, preglomerular microvessels (PGMVs); for the tubules, the thick ascending limb (TAL). Aim 3: Define the Relative Contribution of Trans-EETs/DHTs vs. C/s-EETs/DHTs to the Augmented Renal Vasodilator Response to AA of the SHR vs. Normotensive Rats at Different Levels of Renal Perfusion Pressures.