The red blood cell participates in regulation of the circulation by producing and releasing epoxyeicosatrienoic acids
2012
Jiang, Houli | Anderson, Gail D. | McGiff, John C.
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.
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