The red blood cell participates in regulation of the circulation by producing and releasing epoxyeicosatrienoic acids.

ABSTRACT

Red blood cells (RBCs) have an important function in regulation of the circulation by producing and releasing epoxyeicosatrienoic acids (EETs) in response to a low O2 environment such as encountered in the cardiac microcirculation during exercise. RBCs, in their role as sensors of low pO2, release ATP and critical lipid mediators, the EETs. Both cis- and trans-EETs are synthesized and stored in RBCs and are hydrolyzed by soluble epoxide hydrolases (sEH). The trans-EETs differ from cis-EETs in their higher vascular potencies and more rapid metabolism by sEH. Thus, inhibition of sEH results in greater trans-EET levels and increased positive vascular effects of trans-EETs vs cis-EETs. The trans-EETs are responsible for a significant decline in the elevated blood pressure in the spontaneously hypertensive rat on treatment with a sEH inhibitor to raise EET levels. We predict that trans-EETs and cis-EETs will occupy important therapeutic roles in a broad spectrum of diseases and abnormal physiological conditions such as that resulting from high salt intake and hypertension.