FUNCTION AND REGULATION OF TRANS-eetS

New York Medical College, Valhalla NY

Investigators

Linked publications & trials

Abstract

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