Effect of Novel Soluble Epoxide Hydrolase Inhibitor Against to Pulmonary Arterial Hypertensive Rats

Pulmonary arterial hypertension (PAH) is a disease characterized by elevation of the pulmonary arterial pressure that eventually leads to right ventricular hypertrophy and right heart failure. Vasoconstriction, cell proliferation and vascular inflammation are associated with PAH progression. Epoxyeicosatrienoic acids (EETs) are likely to be signaling molecules to help ameliorate a wide variety of pathological conditions. EETs are known to be metabolized by soluble epoxide hydrolase (sEH). Thus, we assessed the hypothesis that sEH might play a crucial role in PAH and inhibition of sEH activity might ameliorate the development of PAH. In monocrotaline (MCT)-induced PAH model rat, a novel, selective sEH inhibitor were administered daily from the day of MCT injection. There were significant increases in hypertrophy and RVSP in PAH rats group. The increases were significantly attenuated in sEH inhibitor treated groups in a dose-dependent manner. These findings indicate that inhibition of sEH activity may represent a novel therapeutic concept to ameliorate the development of PAH.