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.
Showing the most recent 10 out of 468 publications
