FUNCTION AND REGULATION OF TRANS-EETS

TR-EETS 的功能和监管

• 批准号: 7137839
• 负责人: JOHN C MC GIFF
• 金额: $ 48.27万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7137839
• 关键词: arachidonate; blood pressure; cytochrome P450; eicosanoid metabolism; erythrocytes; hormone regulation /control mechanism; hypertension; kidney metabolism; laboratory rat; oxidative stress; vasomotion

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.

红细胞（RBC）是环氧二碳三烯酸（EETs）的储存库